A new experimental model of muscle pain in humans based on short‐wave diathermy

Abstract

Background

Experimental models of pain in humans are crucial for understanding pain mechanisms. The most often used muscle pain models involve the injection of algesic substances, such as hypertonic saline solution or nerve growth factor, or the induction of delayed onset muscle soreness (DOMS) by an unaccustomed exercise routine. However, these models are either invasive or take substantial time to develop, and the elicited level of pain/soreness is difficult to control. To overcome these shortcomings, we propose to elicit muscle pain by a localized application of short‐wave diathermy (SWD).

Methods

In this crossover study, SWD was administered to eighteen healthy volunteers to the wrist extensor muscle group, with a constant stimulation intensity and up to 4 minutes. Pressure pain threshold (PPT), pinprick sensitivity (PPS) and self‐reported muscle soreness were assessed at baseline and at 0, 30 and 60 minutes after application of SWD.

Results

SWD evoked localized muscle pain/soreness in the wrist extensor muscle group and a decrease of PPT in the treated arm compared with the control arm that lasted for at least 60 minutes, reflecting ongoing hyperalgesia after SWD application. PPS was not significantly altered 30 to 60 min following SWD, suggesting a minimal contribution from skin tissue to sustained hyperalgesia.

Conclusions

SWD was able to elicit muscle soreness and hyperalgesia up to 60 min after its application. Thus, this new model represents a promising tool for investigating muscle pain in humans.

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ARE FUNCTIONAL BRAIN ALTERATIONS PRESENT IN LOW BACK PAIN? A SYSTEMATIC REVIEW OF EEG STUDIES

The central nervous system plays an imperative role in pain processing, and can undergo neuro-plastic changes in response to pain.3,38,42,97,111 The neuro-matrix of pain theory proposed a neural signature of brain networks uniquely responsible for pain processing.81 However, in the last decades this ‘pain matrix’ was questioned as studies showed that involved brain areas are not solely responsible for pain processing, but also for non-painful salient stimuli.70,88,104,120 The main consequence of the introduction of the ‘pain matrix’ is that research regarding pain processing shifted from the peripheral to the central nervous system.

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Perceptual decision parameters and their relation to self-reported pain: a drift diffusion account

One of the most profound developments in modern perception research has been the reformulation of perception as an inferential process. Instead of being a mere readout of sensory input, perception is now understood to be strongly determined by expectations that are generated based on prior knowledge5,10. This critical influence of expectations also applies to the perception of pain. Expectations have been shown to affect pain perception in an experimental context 3,8,15,33 and to predict pain treatment outcomes including long-term disability24 and psychological functioning7,9,11 in clinical populations.

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Inflammatory and neuropathic gene expression signatures of chemotherapy-induced neuropathy induced by vincristine, cisplatin and oxaliplatin in C57BL/6J mice

Vincristine, oxaliplatin, and cisplatin are commonly prescribed chemotherapeutic agents for the treatment of many tumors. However, a main side-effect is chemotherapy-induced peripheral neuropathy (CIPN), which may lead to changes in chemotherapeutic treatment. Although symptoms associated with CIPN are recapitulated by mouse models, there is limited knowledge of how these drugs affect the expression of genes in sensory neurons. The present study carried out a transcriptomic analysis of dorsal root ganglia (DRG) following vincristine, oxaliplatin, and cisplatin treatment with a view to gain insight into the comparative pathophysiological mechanisms of CIPN.

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Post-traumatic toe deformity in a child

A 5 year old boy experienced pain in the little toe of his right foot after falling down the last two steps of a flight of stairs.Initially the diagnosis was a “sprained toe.” No radiograph was taken...

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Sociodemographic and Environmental Factors are Associated with Adolescents’ Pain and Longitudinal Health Outcomes

Pediatric chronic pain has long been examined through the lens of the biopsychosocial model.21,43 However, there is limited research with pediatric populations on the influences of broad social factors such as sociodemographic and environmental variables on chronic pain. Research with adults demonstrates that female sex, minority race/ethnicity, economic disadvantage, neighborhood risk, violence exposure, concerns about safety, and social isolation increases risk for chronic pain.35,45,46 It is critical to better understand the influence of sociodemographic and environmental risk factors on pediatric chronic pain in order to direct prevention and treatment efforts.

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Does the heritability of chronic low back pain depend on how the condition is assessed?

Abstract

Background

Although the influence of genetics on chronic low back pain (LBP) has been previously examined, few studies have investigated whether the impact of genetic factors on LBP depends on how the condition is assessed.

Methods

We investigated the contribution of genetics and environment on chronic LBP: lifetime prevalence, pain intensity (recent and worst), and activity limitation (anytime and recent) in a cross‐sectional study with 1,598 adult twins. All twins answered a self‐reported questionnaire about health‐related questions. We conducted classic twin analyses using Structural Equation Models to estimate the genetic and environmental influences in LBP phenotypes

Results

We found a heritability of 26% (95%CI: 0.09‐0.42) for lifetime chronic LBP; 36% (95%CI: 0.18‐0.52), and 25% (95%CI: 0.03‐0.46) for activity limitation due to chronic LBP, related to lifetime and most recent episode respectively; and heritability of 35% (95%CI: 0.11‐0.55) for pain intensity associated with the most recent episode. Genetics showed no significant influence in pain intensity experienced during the worst LBP episode.

Conclusions

Genetic factors appear to significantly contribute to the variance in chronic LBP including lifetime chronic LBP, activity limitation, and pain intensity associated with more recent episodes of LBP, but not for pain intensity associated with people's report of the worst pain episode. Heritability estimates was fairly similar across different LBP outcomes in a population‐based twin sample, and not dependent on how it is assessed or experienced. However, we could not detect any significant heritability for a report of intensity experienced during the worst LBP episode experienced.

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Sensory Testing Associates With Pain Quality Descriptors During Acute Dental Pain

Abstract

Background

Pain descriptors capture the multidimensional nature of pain and can elucidate underlying pathophysiological mechanisms. This study determined whether the pain descriptors chosen by subjects experiencing acute dental pain associate with the outcomes of two commonly performed dental sensory tests. The goal of the study is to clarify whether pain descriptors are useful in discriminating the underlying biological processes contributing to dental pain.

Methods

Participants (n= 228) presenting with acute toothache underwent standardized clinical dental sensory testing and described their pain in reference to 22 pain quality descriptors. Univariate and 2‐way ANOVA determined the relationship between groups defined by cold detection (positive or negative) and percussion hypersensitivity (painful or not) on the affected tooth, and pain descriptor reporting.

Results

Subjects experiencing painful toothache most frequently reported evoked pain to temperature and chewing, and pain descriptors such as “throbbing” and “aching”. They also reported neuropathic pain descriptors such as “tingling” and “electric shock”. Subjects who detected a cold stimulus (thermal) on the affected tooth, frequently reported high intensity paroxysmal shooting pain compared to those that did not detect cold. By contrast, patients with percussion (mechanical) hypersensitivity on the affected tooth, reported higher levels of global pain intensity at rest and in function, and reported significantly higher intensity “radiating” and “throbbing” pain, than subjects with non‐painful percussion.

Conclusions

The reporting of neuropathic pain descriptors by subjects experiencing acute toothache was more frequent than expected, suggesting that neuropathic mechanisms could contribute to typical toothache pain. Subjects experiencing toothache with mechanical hypersensitivity experience more intense pain overall.

This article is protected by copyright. All rights reserved.

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Strength and range of movement deficits are associated with symptom severity in people scheduled for hip arthroscopy

Abstract

Background

Identifying the physical impairments associated with worse symptoms and greater functional limitations in people with hip pain could enable targeted rehabilitation programmes designed to improve quality of life. The objective of this study was to compare physical characteristics between subgroups of symptoms and functional limitation severity in individuals with hip pain scheduled for arthroscopic surgery.

Methods

Hip range of motion (ROM) and muscle strength were measured in 114 individuals (48 women; aged 32 ± 8 years) with hip pain scheduled for hip arthroscopy. Pain and disability were measured with the International Hip Outcome Tool (iHOT33) subscale of Symptoms and Functional Limitation, and a cluster analysis was used to identify mild, moderate and severe subgroups. Between‐group differences were then evaluated using multivariate analysis of covariance, including sex as a covariate, followed by post hoc testing. Significance was set at 0.05.

Results

Lesser hip muscle strength in all directions was reported in the severe symptoms and functional limitation group compared to the mild group. Hip flexion ROM differed when comparing the moderate to both the mild and severe subgroups. Hip internal rotation did not differ between subgroups of severity.

Conclusions

Individuals with hip pain and severe scores in the iHOT33 subscale of symptoms and functional limitations present with significantly lesser hip muscle strength and hip flexion ROM than individuals with moderate or mild scores. Targeted programmes to improve hip strength and flexion ROM in more severe patients may help reduce symptoms and improve function.

Significance

Individuals with severe hip pain and functional limitation possess significantly lesser muscle strength and flexion ROM than individuals with moderate or mild scores.

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Lumbosacral radicular pain during micturition, defecation or orgasm

Abstract

Background

The objective of this study was to describe, in a cohort of patients followed for bladder, bowel or sexual dysfunctions, the occurrence of radicular pain during micturition, defecation and/or orgasm.

Methods

The study included all patients referred in our neuro‐urology department and who suffered from radicular pain before, during or after micturition, defecation and/or orgasm. Data included demographic and medical variables, urodynamic and perineal electromyographic diagnosis.

Results

A total of 30 patients (men: 70%, mean age 45.4 ± 11.8,) complained of radicular pain before, during or after orgasm (51.4%), micturition (34.3%), or defecation (14.3%). In 30% of cases, radiculopathy was found and was predicted by micturition pain. Other pathologies were as follows: vertebral (16.5%), pelvis and sacral (16.5%), inflammatory central nervous system (10%) lesions and peripheral neuropathies (6.7%). Neurological level of injury was between the lumbar and the sacral level. All spinal cord lesions were lesions of the conus medullaris. Patients also complained of lower urinary tract symptoms (70%), sexual (63.3%) and bowel (60%) disorders. In most cases, the urodynamic diagnosis was neurogenic bladder with peripheral abnormalities and the electromyographic diagnosis was distal neuropathy.

Conclusion

Radicular pain occurring during micturition, defecation or orgasm is a rare condition. The most common underlying lesion seems to be radiculopathy, from lumbar to sacral spine. The presence of these symptoms, in the absence of any known neurological condition, should suggest the practitioner a radiculopathy in most of the cases. In consequence, appropriate additional tests should be offered to these patients.

Significance

Few data are available on sciatica during micturition, defecation or orgasm. This study underlines the need for appropriate tests if a patient complaint from this type of symptom. Indeed, the most common underlying lesion is a radiculopathy but can also be a lesion of conus medullaris.

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Reproducibility of a battery of human evoked pain models to detect pharmacological effects of analgesic drugs

Abstract

Background

Although reproducibility is considered essential for any method used in scientific research, it is investigated only rarely; thus, strikingly little has been published regarding the reproducibility of evoked pain models involving human subjects. Here, we studied the reproducibility of a battery of evoked pain models for demonstrating the analgesic effects of two analgesic compounds.

Methods

A total of 81 healthy subjects participated in four studies involving a battery of evoked pain tests in which mechanical, thermal and electrical stimuli were used to measure pain detection and tolerance thresholds. Pharmacodynamic outcome variables were analysed using a mixed model analysis of variance, and a coefficient of variation was calculated by dividing the standard deviation by the least squares means.

Results

A total of 76 subjects completed the studies. After being administered pregabalin, the subjects’ pain tolerance thresholds in the cold pressor and pressure stimulation tests were significantly increased compared to the placebo group. Moreover, the heat pain detection threshold in UVB‐irradiated skin was significantly increased in subjects who were administered ibuprofen compared to the placebo group. Variation among all evoked pain tests ranged from 2.2% to 30.6%.

Conclusions

Four studies using a similar design showed reproducibility with respect to the included evoked pain models. The relatively high consistency and reproducibility of two analgesics at doses known to be effective in treating clinically relevant pain supports the validity of using this pain test battery to investigate the analgesic activity and determine the active dosage of putative analgesic compounds in early clinical development.

Significance

The consistency and reproducibility of measuring the profile of an analgesic at clinically relevant doses illustrates that this pain test battery is a valid tool for demonstrating the analgesic activity of a test compound and for determining the optimal active dose in early clinical drug development.

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Comparing the effectiveness of integrating ergonomics and motor control to conventional treatment for pain and functional recovery of work‐related neck–shoulder pain: A randomized trial

Abstract

Background

Work‐related neck and shoulder pain (WRNSP) is highly prevalent among patients who seek physiotherapy treatment. Clinicians may tend to focus on teaching home exercises and provide general advice about workplace improvement. The present study investigates the short‐ and long‐term impact of an intervention approach that emphasizes on integrating the motor control re‐education with ergonomic advice.

Methods

Participants diagnosed with WRNSP (n = 101) were randomly assigned into two groups in this randomized controlled trial. The Ergo‐motor Group (EM, n = 51) received an integrated intervention with ergonomic advice/modifications and motor control training individualized for each participant based on their specific work demands. Control Group (CO, n = 50) received treatment for pain relief and general exercises of their necks at a designated physiotherapy clinic. Neck pain intensity and functional outcome measures were assessed before, immediately and 1‐year after the 12‐week intervention programmes. Global Rating of Change Score was used to evaluate the perceived recovery at 1‐year follow‐up.

Results

Both groups reported significant reductions in pain and functional disability scores at post‐intervention (EM, n = 44; CO, n = 42) and 1‐year follow‐up (EM, n = 40; CO, n = 38); however, no significant between‐group differences were found (p > 0.05). Significantly higher rating in global recovery score was reported in EM group at 1‐year follow‐up (p < 0.05).

Conclusions

Intervention integrating ergonomic advice/modification with motor control exercise was found to be equally effective as pain relief and general exercise for pain and functional recovery. However, at 1‐year follow‐up, such integrated approach resulted in significantly better global recovery perceived by people with WRNSP.

Significance

Integrating ergonomic intervention and motor control training achieved similar reduction in pain and functional outcomes compared to conventional physiotherapy at post‐intervention and at 1‐year follow‐up, for patients with moderate level of work‐related neck–shoulder pain and mild degree of functional disability. The Ergo‐motor Group reported significantly better perceived overall recovery at 1‐year follow‐up.

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Neurophysiology and genetics of burning mouth syndrome

Abstract

Background and aims

Neuropathic mechanisms are involved in burning mouth syndrome (BMS), and variation of the dopamine D2 receptor (DRD2) gene contributes to experimental pain perception. We investigated whether neurophysiologic findings differ in BMS patients compared to healthy controls, and whether 957C>T polymorphism of the DRD2 gene influences thermal sensitivity or pain experience in BMS.

Methods

Forty‐five BMS patients (43 women), mean age 62.5 years, and 32 healthy controls (30 women), mean age 64.8 years, participated. Patients estimated pain intensity, interference, suffering and sleep with Numeric Rating Scale. Blink reflex tests of the supraorbital (SON), mental (MN) and lingual (LN) nerves, and thermal quantitative sensory testing were done. The results were analysed with ANOVA. DRD2 gene 957C>T polymorphism was determined in 31 patients, and its effects on neurophysiologic and clinical variables were analysed.

Results

Cool (p = 0.0090) and warm detection thresholds (p = 0.0229) of the tongue were higher in BMS patients than controls. The stimulation threshold for SON BR was higher in patients than in controls (p = 0.0056). The latencies of R2 component were longer in BMS patients than in controls (p = 0.0005) at the SON distribution. Habituation of SON BR did not differ between the groups. The heat pain thresholds were highest (p = 0.0312) in homozygous patients with 957TT, who also reported most interference (p = 0.0352) and greatest suffering (p = 0.0341). Genotype 957CC associated with sleep disturbances (p = 0.0254).

Conclusions

Burning mouth syndrome patients showed thermal hypoesthesia within LN distribution compatible with small fibre neuropathy. The DRD2 957C>T genotype influences perception and experience of BMS pain.

Significance

The results confirm earlier findings of neuropathic pain in BMS. The DRD2 957 C>T genotype influences perception and experience of clinical pain in BMS.

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Depression and suicidal ideation in high‐performance athletes suffering from low back pain: The role of stress and pain‐related thought suppression

Abstract

Background

Depression and suicidal ideation are important health problems in athletes suffering from pain. Dysfunctional pain cognitions, that is, pain‐related thought suppression (PTS), may play an important role in their aetiology. Thought suppression was shown to increase depressive mood, particularly in highly stressed individuals. This cross‐sectional study examines the relationship between PTS and stress on depression and suicidal ideation in athletes with pain.

Methods

A total of 159 athletes with non‐specific low back pain completed a set of questionnaires to measure PTS, depression and stress. Participants were split into groups with high and low stress, and high and low PTS. Two‐way ANOVA calculated main effects for PTS, stress and a PTS*stress interaction, with depressive symptoms as dependent. Subsequently, distribution tests were calculated, investigating if the presence of clinically relevant depression and suicidal ideation is dependent of conditions of high/low PTS and stress.

Results

A main effect of stress demonstrated higher depression scores in highly stressed athletes. Further, a significant PTS*stress interaction showed elevated depression scores in athletes with high PTS and high stress. Distribution analysis revealed positive associations between PTS, stress and depression, with depression being most frequent among athletes with high PTS and high stress. Suicidal ideation was not significantly associated with PTS and only weakly correlated with stress.

Conclusions

Our findings show that PTS is the most common pain response in athletes with pain. The results indicate a higher prevalence of depression and elevated depressive symptoms in athletes experiencing high stress, seemingly more pronounced when highly engaging in PTS.

Significance

This study contributes to the understanding of depression in athletes with pain, suggesting stress and pain‐related thought suppression to increase symptoms and prevalence of depression. As athletes often experience acute or chronic pain, understanding the impact of pain cognitions on health outcomes is an important step in the optimization of treatments.

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Cold‐evoked potentials versus contact heat‐evoked potentials—Methodological considerations and clinical application

Abstract

Background

Previous studies investigated cold‐evoked potentials (CEPs) for the assessment of the integrity of cold‐mediating A‐delta fibres and the spinothalamic tract. Nevertheless, several methodological questions remained unanswered to proceed to clinical application. How do latencies and amplitudes vary between CEPs and contact heat‐evoked potentials (CHEPs)? Are there differences between variable and fixed thermode positions or between glabrous and hairy skin? Are CEPs recordable in patients with abnormal cold processing?

Methods

A total of 16 healthy subjects were tested with CEPs and CHEPs at the face, hand and foot. Variable and fixed thermode positions, hairy and glabrous skin were compared. Three patients with abnormal cold processing were tested with CEPs and quantitative sensory testing.

Results

Compared to CEPs, CHEPs latencies were significantly longer at all locations, amplitudes were significantly larger at the face and the hand whilst comparable at the foot. CEPs and CHEPs did not differ significantly between variable and fixed thermode positions using inter stimulus intervals of 8–12 s. CEP latencies were increased by around 20% at the glabrous skin. Patients with known abnormal cold processing (central pain, polyneuropathy, Fabry's disease) showed increased N2 latencies as compared to normal controls.

Conclusions

Inter stimulus intervals of 8‐12 s allow the use of a fixed thermode position for reliable CEPs/CHEPs recording. Hairy skin stimulation results in faster latencies as compared to glabrous skin, without influencing EP amplitudes. In patients with abnormal cold processing, CEPs are recordable and increased latencies may be expected as compared to healthy controls and the healthy contralateral side.

Significance

Cold‐evoked potentials are an innovative, non‐invasive technique to assess cold detection and processing objectively. This study shows that CEP can be recorded from the hairy and glabrous skin, regardless of using fixed or variable thermode positions. Loss of A‐delta fibre function leads to an increased CEP latency, consistent with loss of cold detection in the QST.

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Complete withdrawal is the most feasible treatment for medication‐overuse headache: A randomized controlled open‐label trial

Abstract

Background

Complete stop of acute medication and/or migraine medication for treatment of medication‐overuse headache (MOH) has previously been reported more effective in reducing headache days and migraine days per month compared with restricted intake of acute medication. However, it is unknown whether complete stop or restricted intake is the most feasible treatment for patients.

Objectives

To investigate whether feasibility of withdrawal in MOH is different between complete stop of acute medication and restricted intake, and whether reductions in headache‐related medication dependence, anxiety and depression differ between the treatments.

Methods

Medication‐overuse headache patients were included in a prospective, open‐label, outpatient study and randomized to two months of withdrawal with either no analgesics or acute migraine medication (programme A) or acute medication restricted to 2 days/week (programme B). After 6 and 12 months, patients graded feasibility of withdrawal. Dependence was measured by Severity of Dependence Scale (SDS), while anxiety and depression were measured by Hospital Anxiety and Depression Scale (HADS).

Results

We included 72 MOH patients with primary migraine and/or tension‐type headache. Forty‐nine completed withdrawal and the SDS questionnaire at 12‐month follow‐up, and the feasibility of withdrawal was significantly higher in programme A compared to programme B (p < 0.001). At 12 months, the dependence was reduced by 44% in programme A compared to 26% in programme B (p = 0.053), while the anxiety score was reduced by 32% and 11%, respectively (p = 0.048).

Conclusions

Withdrawal with complete stop of acute medication was more feasible and most effective in reducing headache‐related anxiety compared with restricted intake.

Significance

A complete stop of all analgesics is the most effective treatment for MOH regarding reduction in headache days but has often been regarded as too challenging for patients. However, in this study, complete stop appears to be more feasible compared with restricted intake of analgesics seen from the patients’ perspective.

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Contralateral segmental transcutaneous electrical nerve stimulation inhibits nociceptive flexion reflex in healthy participants

Abstract

Background

Transcutaneous electrical nerve stimulation (TENS) is a non‐invasive treatment to relieve pain. Contralateral TENS (i.e. TENS administered to the contralateral side of a painful body part) is beneficial when TENS cannot be directly applied to pain site, such as in cases of trauma. Although TENS produces segmental analgesia in an ipsilateral limb, it has been unclear whether TENS produces higher analgesic effects in the contralateral segmental area. The aim of the present study was to investigate the analgesic effects of TENS in contralateral segmental or extra‐segmental areas on physiological and subjective pain outcomes, using a nociceptive flexion reflex (NFR) method.

Methods

We randomly allocated 60 healthy participants to three groups: contralateral segmental TENS (CS‐TENS); contralateral extra‐segmental TENS (CE‐TENS); and contralateral placebo TENS (CP‐TENS). CS‐TENS was applied to right superficial sural nerve and CE‐TENS was applied to the right superficial femoral nerve, each for 30 minutes. The magnitude of the NFR elicited by electrical stimulation of the left sural nerve was measured at baseline and at three subsequent 10‐minute intervals. Subjective pain intensity was measured simultaneously with a visual analogue scale (VAS).

Results

At 30 min, the NFR magnitude of CS‐TENS group was significantly lower than that of the CP‐TENS group (p = 0.021). There were no significant differences in VAS scores among the groups at any time point.

Conclusions

Our findings suggest that CS‐TENS inhibited NFR. Although there was no significant between‐group difference in subjective pain intensity, factors such as a placebo effect probably impacted it.

Significance

Our findings provide support for the contralateral approach at stimulation sites when TENS cannot be directly administered to a pain site (e.g. due to disease or trauma).

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Sex matters in complex regional pain syndrome

Abstract

Background

Complex regional pain syndrome (CRPS) is much more prevalent in women than men but potential differences in clinical phenotype have not been thoroughly explored to date. Differences in the clinical presentation between sexes may point at new avenues for a more tailored management approach of CRPS. We therefore explored if in CRPS, the patient's sex is associated with differences in clinical and psychological characteristics.

Methods

In this cross‐sectional study of 698 CRPS patients (599 females) fulfilling the Budapest clinical or research criteria, CRPS signs and symptoms, CRPS severity, pain (average pain intensity in the previous week and McGill pain rating index), pain coping (Pain Coping Inventory), physical limitations (Radboud Skills Questionnaire (upper limb), Walking and Rising questionnaire (lower limb)), anxiety and depression (Hospital Anxiety and Depression scale) and kinesiophobia (Tampa scale for kinesiophobia) were evaluated.

Results

Male CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia.

Conclusion

Sex‐related differences are present in CRPS, but the effect is generally small and mainly concerns psychological functioning. A greater awareness of sex‐specific factors in the management of CRPS may contribute to achieving better outcomes.

Significance

What is known? Nonsex‐specific clinical data of CRPS patients. What is new? Male CRPS patients used more often extreme words to describe the affective qualities of pain, used more passive pain coping strategies, and were more likely to suffer from depression and kinesiophobia.

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A combination pharmacotherapy of tapentadol and pregabalin to tackle centrally driven osteoarthritis pain

Abstract

Background

Many Osteoarthritis (OA) patients report with clinical features to their pain that cannot be explained by purely peripheral mechanisms. Yet, the analgesic agents available that tackle centrally driven chronic pain often provide only partial pain relief, or have dose‐limiting side effects. We explored a combination therapy of the centrally acting analgesic agents tapentadol and pregabalin, to investigate if they could be used in combination to provide superior analgesia.

Methods

Using electrophysiological single‐unit recordings taken from spinal wide dynamic range neurons, Diffuse Noxious Inhibitory Controls (DNIC) were assessed as a marker of potential changes in descending controls in a monoiodoacetate (MIA) model of OA. We investigated if a subcutaneous injection of tapentadol or pregabalin, both alone and in combination, inhibited neuronal responses and restored the expression of DNIC, quantified as a reduction in neuronal firing in the presence of a conditioning noxious stimulus.

Results

Tapentadol restored DNIC‐induced neuronal inhibition in MIA animals, while pregabalin inhibited pre‐conditioned mechanically evoked neuronal responses but did not restore DNIC. Given in combination, tapentadol and pregabalin restored DNIC expression and also inhibited spinal neuronal responses.

Conclusions

We propose that there is both central sensitization and an imbalance in inhibitory and facilitatory descending controls in MIA animals. The combination therapy of tapentadol and pregabalin restored descending noradrenergic inhibitory tone and also inhibited nociceptive transmission at the level of the spinal cord.

Significance

This study shows that pregabalin and tapentadol target different mechanisms of centrally driven chronic pain associated with osteoarthritis, and that when administered together can restore descending inhibitory tone whilst also tackling spinal neuronal hyperexcitability and may therefore provide superior analgesia.

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Patients’ Global Impression of Change in the management of peripheral neuropathic pain: Clinical relevance and correlations in daily practice

Abstract

Background

Patient‐Reported Outcome (PRO) instruments have been developed to evaluate pain management in daily practice; the Patients’ Global Impression of Change (PGIC) is particularly recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. The prospective non‐interventional multicenter PRO‐QURE study aimed at assessing correlations between PGIC and pain measurements and treatment effects in patients followed in French pain centres.

Methods

Respectively, 495 and 379 patients with peripheral neuropathic pain initiating treatment with capsaicin 8% cutaneous patch(es) (female, 62.6%; mean age, 54.0 ± 14.8 years; post‐surgical or traumatic pain, 52.7%; mean pain duration, 42.2 ± 54.1 months; DN4 score >4, 92.9%) completed the PGIC and several other PRO instruments before (baseline) and 3 months (M3) after treatment application.

Results

At M3, improvement (“much improved” or “very much improved”) was observed in 23.0% of patients, associated with decreases of −3.0 ± 2.2, −2.5 ± 2.4, and −23.1 ± 19.7 in BPI pain intensity, BPI pain interference and NPSI total scores, respectively. The highest Spearman's rank correlation coefficients with PGIC were found for pain intensity (BPI: r = −0.479, p < 0.001), satisfaction with current state (Patient Acceptable Symptomatic State: r = 0.455, p < 0.001), and treatment effectiveness (TSQM: r = 0.431, p < 0.001); correlation coefficients were lower for all NPSI scores, BPI pain interference score, HAD scores and EQ‐5D‐3L index.

Conclusions

In daily clinical practice, significant improvement in peripheral neuropathic pain, as assessed by PGIC scores, significantly correlated with changes in well‐established measures of pain intensity, pain interference with activities of daily living, mood and quality of life, confirming its clinical interest as PRO measure in real‐world conditions.

Significance

Clinically important improvement in peripheral neuropathic pain, as assessed by PGIC scores, significantly correlated with well‐established measures of pain intensity, pain interference in daily life and treatment efficacy. This result, associated with the ease of administration and scoring, encourages the widespread use of the PGIC in daily practice.

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Lumbar range of motion in chronic low back pain is predicted by task‐specific, but not by general measures of pain‐related fear

Abstract

Background

Most studies fail to show an association between higher levels of pain‐related fear and protective movement behaviour in patients with chronic low back pain (CLBP). This may be explained by the fact that only general measures of pain‐related fear have been used to examine the association with movement patterns. This study explored whether task‐specific, instead of general measures of pain‐related fear can predict movement behaviour.

Methods

Fifty‐five patients with CLBP and 54 healthy persons performed a lifting task while kinematic measurements were obtained to assess lumbar range of motion (ROM). Scores on the Photograph Daily Activities Series‐Short Electronic Version (PHODA‐SeV), Tampa Scale for Kinesiophobia and its Activity Avoidance and Somatic Focus subscales were used as general measures of pain‐related fear. The score on a picture of the PHODA‐SeV, showing a person lifting a heavy object with a bent back, was used as task‐specific measure of pain‐related fear.

Results

Lumbar ROM was predicted by task‐specific, but not by general measures of pain‐related fear. Only the scores on one other picture of the PHODA‐SeV, similar to the task‐specific picture regarding threat value and movement characteristics, predicted the lumbar ROM. Compared to healthy persons, patients with CLBP used significantly less ROM, except the subgroup with a low score on the task‐specific measure of pain‐related fear, who used a similar ROM.

Conclusions

Our results suggest to use task‐specific measures of pain‐related fear when assessing the relationship with movement. It would be of interest to investigate whether reducing task‐specific fear changes protective movement behaviour.

Significance

This study shows that lumbar range of motion in CLBP is predicted by task‐specific, but not by general measures of pain‐related fear. This suggests that both in clinical practice and for research purposes, it might be recommended to use task‐specific measures of pain‐related fear when assessing the relationship with movement behaviour. This may help to disentangle the complex interactions between pain‐related fear, movement and disability in patients with CLBP.

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Comments on the paper by Nielsen et al. entitled “Intraoperative S‐ketamine for the reduction of opioid consumption and pain one year after spine surgery: A randomized clinical trial of opioid‐dependent patients”

European Journal of Pain, Volume 23, Issue 6, Page 1221-1221, July 2019.

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Authors’ Reply to the Letter to the Editor from Mukhdomi and Kendall

European Journal of Pain, Volume 23, Issue 6, Page 1222-1222, July 2019.

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Issue Information

European Journal of Pain, Volume 23, Issue 6, Page 1045-1046, July 2019.

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Revisiting established medicines: An overview of systematic reviews about ibuprofen and paracetamol for treating pain in children

Abstract

Background and objective

We explored how systematic reviews evaluated paracetamol and ibuprofen for treating pain in children, as these two non‐opioid analgesics are well‐established medicines included in most national essential medicines lists.

Databases and data treatment

We carried out an overview of systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions (PROSPERO registration: 42016045367). We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews (CDSR) and Database of Reviews of Effects (DARE) up to 23 August 2017. We used AMSTAR checklist to analyse methodological quality of included SRs.

Results

We found 17 SRs with 72 unique RCTs; the majority of those trials included under 100 children. Positive conclusive evidence was found in only one SR, regarding safety of paracetamol. Conclusions of other SRs for efficacy and safety of ibuprofen and paracetamol were inconclusive, unclear, or there was no opinion. Only one SR analysed efficacy of ibuprofen and other non‐steroidal anti‐inflammatory drugs (NSAIDs) in chronic pain and the conclusion was that there was no evidence from RCTs that NSAIDs were effective for chronic non‐cancer pain in children and adolescents. Most of the SRs addressed very narrow questions, included few trials, with few children and were of low or medium methodological quality.

Conclusions

Most SRs on two relevant medicines have inconsistent conclusions and doubt upon their effectiveness. Instead of focusing on very narrow questions, SRs should examine more comprehensive research topics to obtain a general sense of consistency, particularly when analysing established medicines.

Significance

Evidence behind two analgesics—ibuprofen and paracetamol—that are well‐established medicines for children in most countries appears limited, judging by the systematic reviews. The discrepancy between clinical use and the extensive evidence we reviewed may be a result of the selective criteria in the reviews examined. We need new, and better evidence syntheses supporting the use of these two medicines in wide indications regarding pain in children.

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Non‐pharmacological management of persistent headaches associated with neck pain: A clinical practice guideline from the Ontario protocol for traffic injury management (OPTIMa) collaboration

Abstract

Objectives

To develop an evidence‐based guideline for the non‐pharmacological management of persistent headaches associated with neck pain (i.e., tension‐type or cervicogenic).

Methods

This guideline is based on systematic reviews of high‐quality studies. A multidisciplinary expert panel considered the evidence of clinical benefits, cost‐effectiveness, societal and ethical values, and patient experiences when formulating recommendations. Target audience includes clinicians; target population is adults with persistent headaches associated with neck pain.

Results

When managing patients with headaches associated with neck pain, clinicians should (a) rule out major structural or other pathologies, or migraine as the cause of headaches; (b) classify headaches associated with neck pain as tension‐type headache or cervicogenic headache once other sources of headache pathology has been ruled out; (c) provide care in partnership with the patient and involve the patient in care planning and decision making; (d) provide care in addition to structured patient education; (e) consider low‐load endurance craniocervical and cervicoscapular exercises for tension‐type headaches (episodic or chronic) or cervicogenic headaches >3 months duration; (f) consider general exercise, multimodal care (spinal mobilization, craniocervical exercise and postural correction) or clinical massage for chronic tension‐type headaches; (g) do not offer manipulation of the cervical spine as the sole form of treatment for episodic or chronic tension‐type headaches; (h) consider manual therapy (manipulation with or without mobilization) to the cervical and thoracic spine for cervicogenic headaches >3 months duration. However, there is no added benefit in combining spinal manipulation, spinal mobilization and exercises; and (i) reassess the patient at every visit to assess outcomes and determine whether a referral is indicated.

Conclusions

Our evidence‐based guideline provides recommendations for the conservative management of persistent headaches associated with neck pain. The impact of the guideline in clinical practice requires validation.

Significance

Neck pain and headaches are very common comorbidities in the population. Tension‐type and cervicogenic headaches can be treated effectively with specific exercises. Manual therapy can be considered as an adjunct therapy to exercise to treat patients with cervicogenic headaches. The management of tension‐type and cervicogenic headaches should be patient‐centred.

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Time for change: an experimental investigation of chronic pain patients' emotional and attitudinal responses to simulated opioid-tapering advice

Clinicians report reluctance to deliver opioid-tapering advice to patients with chronic pain, in part due to concerns that patients will be angry and dissatisfied. An experiment was conducted to examine chronic pain patients' emotional and attitudinal responses to simulated opioid-tapering advice. Patients scheduled for an initial assessment at a tertiary pain clinic and currently taking opioid medications for pain (N = 196) were randomly assigned to view video footage of a standardized patient receiving 1 of 3 forms of treatment advice: (1) stay on current medication (2) change to a different pain medication, or (3) taper off pain medications and participate in a CBT-based pain self-management program. Participants reported how positive/enthusiastic, anxious/worried, and angry/irritable they felt in response to the simulated treatment advice, and how satisfied with and willing they would be to accept and follow the advice. Participants expressed more positive emotional and attitudinal responses to simulated opioid-tapering advice than to simulated opioid-maintenance advice. Furthermore, participants' responses to simulated opioid-tapering and opioid-change advice were not significantly different, suggesting that participants responded positively to the prospect of change in treatment strategy. Additional analyses revealed that participants with a longer history of chronic pain and opioid use responded less positively to simulated opioid-tapering advice. The results of this study contribute to our understanding of factors that may shape chronic pain patients' responses to opioid-tapering advice and suggest that patients may respond more positively to opioid-tapering advice if it is presented together with an alternative treatment approach.

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Somatotopically specific primary somatosensory connectivity to salience and default mode networks encodes clinical pain

Although several studies have found that chronic pain is characterized by increased cross-network connectivity between salience network, sensorimotor network, and default mode network (DMN), a large sample-size investigation allowing for a more reliable evaluation of somatotopic specificity and subgroup analyses with linkage to clinical pain intensity has been lacking. We enrolled healthy adults and a large cohort of patients (N = 181) suffering from chronic low back pain (cLBP). To specifically link brain connectivity with clinical pain intensity, patients were scanned at baseline and after performing physical maneuvers that exacerbated pain. Compared with healthy adults, patients with cLBP demonstrated increased connectivity between the functionally localized back representation in the primary somatosensory cortex (S1back) and both salience network and DMN. Pain exacerbation maneuvers increased S1back connectivity to salience network regions, but decreased connectivity to DMN, with greater pain intensity increase associated with greater shifts in these connectivity patterns. Furthermore, only in patients with cLBP reporting high pain catastrophizing, DMN connectivity was increased to a cardinal node of the salience network, anterior insula cortex, which was correlated with increased postmaneuver pain in this cLBP subgroup. Hence, increased information transfer between salience processing regions, particularly anterior insula, and DMN may be strongly influenced by pain catastrophizing. Increased information transfer between the salience network and S1 likely plays an important role in shifting nociceptive afference away from self-referential processing, reallocating attentional focus, and affective coding of nociceptive afference from specific body areas. These results demonstrate S1 somatotopic specificity for cross-network connectivity in encoding clinical back pain and moderating influence of catastrophizing for DMN/insula connectivity.

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RNA-seq data in pain research–an illustrated guide

No abstract available

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Mineralized Collagen Modified Polymethyl Methacrylate Bone Cement for Osteoporotic Compression Vertebral Fracture at 1-Year Follow-up

Study Design. Retrospective comparative study. Objective. This study aimed to compare the clinical effects and imaging features of polymethyl methacrylate (PMMA) bone cement with and without mineralized collagen (MC) in percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). Summary of Background Data. PKP with PMMA is widely performed for OVCF. However, numerous complications have also been reported about the PMMA bone cement. Moreover, PMMA bone cement with and without MC have not been compared with respect to their postoperative efficacy and long-term follow-up. Methods. From July 2016 to July 2017, 105 OVCF patients were randomly divided into two groups based on their PKP treatment: MC-PMMA group and PMMA group. Clinical operation, cement leakage, Oswestry Disability Index, visual analog scale, height of the fractured vertebrae, Cobb angle, refracture of the adjacent vertebra, recompression, and computed tomography values of the injured vertebra were compared between the two groups postoperatively and after 1-year follow-up. Results. Clinical operation showed no differences between the two groups. Visual analog scale scores, Oswestry Disability Index scores, and Cobb angles showed statistically significant differences between the two groups after 1-year follow-up. The height of the vertebral body showed significant difference at 3 days postoperatively and preoperatively in each group and significant difference after 1 year between the two groups. The rate of refracture and leakage of the MC-PMMA group was lower than that of the PMMA group. The computed tomography value of the MC-PMMA group was obviously higher than that of the PMMA group after 1-year follow-up. Conclusion. MC-modified PMMA did not change the beneficial properties of PMMA. This new bone cement has better biocompatibility, can form a stable structure in the vertebral body, and improve the prognosis of patients by reducing pain and reoperation. Level of Evidence: 3

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Poor Baseline Mental Health Does Not Influence Improvement in Patient-reported Outcomes, Satisfaction, and Return to Work Two Years After Single-level Anterior Cervical Discectomy and Fusion

Study Design. Retrospective study using prospectively collected registry data. Objective. The authors examine the influence of preoperative mental health on outcomes after anterior cervical discectomy and fusion (ACDF) and determine the impact of ACDF on postoperative mental health. Summary of Background Data. While studies have reported a negative correlation between preoperative mental health and outcomes following lumbar spine surgery, the influence on outcomes following cervical spine surgery remains relatively understudied. Methods. Prospectively collected registry data of 104 patients who underwent single-level ACDF for cervical spondylotic myelopathy were reviewed. Patients were dichotomized into top and bottom halves based on preoperative SF-36 MCS (Mental Component Summary) using a cutoff of 48. Outcomes assessed were visual analogue scale for neck pain, arm pain, AAOS Neck Pain and Disability, Neurogenic Symptoms, Neck Disability Index, Short-Form 36, Japanese Orthopaedic Association myelopathy score, return to work, return to function, satisfaction and expectation fulfilment up to 2 years postoperatively. Results. The preoperative MCS was 37.5 ± 8.1 and 57.4 ± 6.3 in the Low and High MCS groups respectively (P < 0.001). The Low MCS group had poorer preoperative scores (P < 0.05). There was no significant difference in length of stay or comorbidities (P > 0.05). The High MCS group had less neck pain (P = 0.002) and showed a trend towards lower Neck Disability Index (P = 0.062) at 2 years. The Low MCS group demonstrated greater improvement in Japanese Orthopaedic Association (P = 0.007) and similar improvement in other scores (P > 0.05). There was no significant difference in proportion that achieved minimal clinically important difference for each score (P > 0.05). Both groups had similar rates of return to work, return to function, expectation fulfilment, and satisfaction (P > 0.05). Lower preoperative MCS was predictive of greater improvement in MCS (r = −0.477, P < 0.001). Conclusion. Despite relatively greater pain and disability at 2 years, patients with poor baseline mental health experienced similar improvement in clinical outcomes, return to work, and satisfaction rates. Level of Evidence: 3

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Long-term Tumor Control With Radiotherapy for Symptomatic Hemangioma of a Vertebral Body

Study Design. Retrospective outcomes review. Objective. To analyze and report long-term outcomes in a cohort of patients treated with radiotherapy (RT) for symptomatic hemangioma of a vertebral body. Summary of Background Data. Data are scarce on the rate of tumor control with long-term (>5 yr) follow-up after RT for symptomatic hemangioma of a vertebral body. Methods. We retrospectively reviewed the medical records of patients treated at our institution between 1971 and 2008 for symptomatic hemangioma of a vertebral body, updated their follow-up, analyzed complications, and calculated the tumor control rate. Tumor control by imaging was defined as no increase in tumor size on computed tomography (CT) or magnetic resonance (MR) scan. Clinical tumor control was defined as no symptoms of recurrent tumor. Results. Ten patients were eligible for analysis. All patients had pain from visible hemangioma at the time of radiotherapy for which surgical resection or interventional radiology procedures were likely to result in high morbidity. Tumors were located in the lumbar (40%), thoracic (50%), or cervical (10%) areas of the spine. The mean radiotherapy dose delivered was 47 Gy. Mean imaging follow-up after completion of radiotherapy was 8.1 years; mean clinical follow-up was 21.2 years. The tumor control rate was 90% (9/10). One patient who may have developed a tumor recurrence had radiographic and clinical evidence of tumor progression 30 years after radiotherapy. The actuarial rate of tumor control was 100% at 5, 10, 20, and 25 years. There was no grade more than or equal to three treatment toxicities, no evidence of malignant transformation, and no evidence of second tumors in treatment area (with the possible exception of the one tumor recurrence). Conclusion. RT for symptomatic hemangioma of the spine provides long-term tumor control with a low risk of serious complications. Radiotherapy is a good option when surgery or an interventional radiology procedure is high-risk. Our preferred dose is 45 Gy at 1.8 Gy/fraction. Level of Evidence: 4

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Negative Effects of Long-duration Spaceflight on Paraspinal Muscle Morphology

Study Design. Prospective case series. Objective. Determine the extent of paraspinal muscle cross-sectional area (CSA) and attenuation change after long-duration spaceflight and recovery on Earth. Determine association between in-flight exercise and muscle atrophy. Summary of Background Data. Long-duration spaceflight leads to marked muscle atrophy. However, another negative consequence of disuse is intramuscular fatty infiltration. Notably, few studies have investigated the effects of spaceflight on intramuscular fatty infiltration, or how muscle atrophy is associated with in-flight exercise. Methods. We analyzed computed tomography scans of the lumbar spine (L1/L2) from 17 long-duration astronauts and cosmonauts to determine paraspinal muscle CSA and attenuation. Computed tomography scans were collected preflight, postflight, 1-year postflight, and, in a subset, 2 to 4 years postflight. We measured CSA (mm2) and attenuation (Hounsfield Units) of the erector spinae (ES), multifidus (MF), psoas (PS), and quadratus lumborum (QL) muscles. We used paired t tests to compare muscle morphology at each postflight time point to preflight values and Pearson correlation coefficients to determine the association between muscle changes and in-flight exercise. Results. ES, MF, and QL CSA and attenuation were significantly decreased postflight compared with preflight (−4.6% to −8.4% and −5.9% to −8.8%, respectively, p < 0.05 for all). CSA of these muscles equaled or exceeded preflight values upon Earth recovery, however QL and PS attenuation remained below preflight values at 2 to 4 years postflight. More resistance exercise was associated with less decline in ES and MF CSA, but greater decline in PS CSA. Increased cycle ergometer exercise was associated with less decline of QL CSA. There were no associations between in-flight exercise and muscle attenuation. Conclusion. Both CSA and attenuation of paraspinal muscles decline after long-duration spaceflight, but while CSA returns to preflight values within 1 year of recovery, PS and QL muscle attenuation remain reduced even 2 to 4 years postflight. Spaceflight-induced changes in paraspinal muscle morphology may contribute to back pain commonly reported in astronauts. Level of Evidence: 4

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Preoperative Opioids and 1-year Patient-reported Outcomes After Spine Surgery

Study Design. Longitudinal Cohort Study. Objective. Determine 1-year patient-reported outcomes associated with preoperative chronic opioid therapy and high-preoperative opioid dosages in patients undergoing elective spine surgery. Summary of Background Data. Back pain is the most disabling condition worldwide and over half of patients presenting for spine surgery report using opioids. Preoperative dosage has been correlated with poor outcomes, but published studies have not assessed the relationship of both preoperative chronic opioids and opioid dosage with patient-reported outcomes. Methods. For patients undergoing elective spine surgery between 2010 and 2017, our prospective institutional spine registry data was linked to opioid prescription data collected from our state's Prescription Drug Monitoring Program to analyze outcomes associated with preoperative chronic opioid therapy and high-preoperative opioid dosage, while adjusting for confounders through multivariable regression analyses. Outcomes included 1-year meaningful improvements in pain, function, and quality of life. Additional outcomes included 1-year satisfaction, return to work, 90-day complications, and postoperative chronic opioid use. Results. Of 2128 patients included, preoperative chronic opioid therapy was identified in 21% and was associated with significantly higher odds (adjusted odds ratio [95% confidence interval]) of not achieving meaningful improvements at 1-year in extremity pain (aOR:1.5 [1.2–2]), axial pain (aOR:1.7 [1.4–2.2]), function (aOR:1.7 [1.4–2.2]), and quality of life (aOR:1.4 [1.2–1.9]); dissatisfaction (aOR:1.7 [1.3–2.2]); 90-day complications (aOR:2.9 [1.7–4.9]); and postoperative chronic opioid use (aOR:15 [11.4–19.7]). High-preoperative opioid dosage was only associated with postoperative chronic opioid use (aOR:4.9 [3–7.9]). Conclusion. Patients treated with chronic opioids prior to spine surgery are significantly less likely to achieve meaningful improvements at 1-year in pain, function, and quality of life; and less likely to be satisfied at 1-year with higher odds of 90-day complications, regardless of dosage. Both preoperative chronic opioid therapy and high-preoperative dosage are independently associated with postoperative chronic opioid use. Level of Evidence: 2

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Moderators of mindfulness meditation, cognitive therapy, and mindfulness-based cognitive therapy for chronic low back pain: A test of the Limit, Activate and Enhance model

Psychosocial treatments for chronic low back pain (CLBP) – including cognitive and mindfulness-based approaches – significantly improve pain-related outcomes.7,15,20,25,28,31,36,45,51 However, there is substantial individual variability in treatment response.48,51 To address the issue of treatment outcome variability, and to optimize treatment benefits, there has been a call to identify the person factors that moderate response to different treatments.

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Re: Early Physical Therapy for Acute Low Back Pain May Not Reduce Health Services Utilization, Costs, and Opioid Use

Publication date: July 2019

Source: Archives of Physical Medicine and Rehabilitation, Volume 100, Issue 7

Author(s): Elizabeth Arnold, Adam Goode, Derek Clewley

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Early Physical Therapy for Acute Low Back Pain May Not Reduce Health Services Utilization, Costs, and Opioid Use

Publication date: July 2019

Source: Archives of Physical Medicine and Rehabilitation, Volume 100, Issue 7

Author(s): Giovanni Ferreira, Hugo Amorim, Chris Maher

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Rehabilitation Exercises Reduce Reinjury Post Ankle Sprain, But the Content and Parameters of an Optimal Exercise Program Have Yet to Be Established: A Systematic Review and Meta-analysis

Publication date: July 2019

Source: Archives of Physical Medicine and Rehabilitation, Volume 100, Issue 7

Author(s): Chris M. Bleakley, Jeffrey B. Taylor, Steven L. Dischiavi, Cailbhe Doherty, Eamonn Delahunt

Abstract

Objectives

To determine if exercise-based rehabilitation reduces reinjury following acute ankle sprain. Our secondary objective was to assess if rehabilitation efficacy varies according to exercise content and training volume.

Data Sources

The following electronic databases were searched: EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, and Physiotherapy Evidence Database (PEDro).

Study Selection

Randomized controlled trials investigating the effect of exercise-based rehabilitation programs on reinjury and patient-reported outcomes (perceived instability, function, pain) in people with an acute ankle sprain. No restrictions were made on the exercise type, duration, or frequency. Exercise-based programs could have been administered in isolation or as an adjunct to usual care. Comparisons were made to usual care consisting of 1 or all components of PRICE (protection, rest, ice, compression, elevation).

Data Extraction

Effect sizes with 95% CIs were calculated in the form of mean differences for continuous outcomes and odds ratios (ORs) for dichotomous outcomes. Pooled effects were calculated for reinjury prevalence with meta-analysis undertaken using RevMan software.

Data Synthesis

Seven trials (n=1417) were included (median PEDro score, 8/10). Pooled data found trends toward a reduction in reinjury in favor of the exercise-based rehabilitation compared with usual care at 3-6 months (OR, 0.87; 95% CI, 0.48-1.58) with significant reductions reported at 7-12 months (OR, 0.53; 95% CI, 0.38-0.73). Sensitivity analysis based on pooled reinjury data from 2 high quality studies (n=629) also found effects in favor of exercise-based rehabilitation at 12 months (OR, 0.60; 95% CI, 0.49-0.89). Training volume differed substantially across rehabilitation programs with total rehabilitation time ranging from 3.5-21 hours. The majority of rehabilitation programs focused primarily on postural balance or strength training.

Conclusions

Exercise-based rehabilitation reduces the risk of reinjury following acute ankle sprain when compared with usual care alone. There is no consensus on optimal exercise content and training volume in this field. Future research must explicitly report all details of administered exercise-based rehabilitation programs.

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Allocation Concealment and Intention-To-Treat Analysis Do Not Influence the Treatment Effects of Physical Therapy Interventions in Low Back Pain Trials: a Meta-epidemiologic Study

Publication date: July 2019

Source: Archives of Physical Medicine and Rehabilitation, Volume 100, Issue 7

Author(s): Matheus Oliveira de Almeida, Bruno Tirotti Saragiotto, Chris Maher, Leonardo Oliveira Pena Costa

Abstract

Objective

To evaluate if allocation concealment and intention-to-treat (ITT) analysis influence the treatment effects of physical therapy interventions in low back pain (LBP) trials.

Data Sources

We searched on PubMed, Embase, Cochrane Database of Systematic Reviews, Physiotherapy Evidence Database (PEDro), and CINAHL up to February 2017.

Study Selection

We included LBP trials that compared physical therapy interventions to placebo or no intervention or minimal intervention with pain or disability outcomes.

Data Extraction

Information about allocation concealment and ITT analysis was extracted from PEDro and pain and disability outcomes converted to a 0-100 scale. A meta-regression was performed to evaluate the influence of these methodological features of interest on treatment effects. Other covariates included in the meta-regression were sample size and sequence generation.

Data Synthesis

We identified 128 eligible trials (pooled N=20,555 participants). A total of 44.5% of the trials achieved allocation concealment, while 32% performed ITT analysis. Meta regression analyses showed no influence of allocation concealment on treatment effects for pain (regression coefficient 0.009; 95% confidence interval [CI] -2.91 to 2.91) and disability (regression coefficient 1.13; 95% CI -1.35 to 3.62), and no influence of ITT analysis for pain (regression coefficient 1.38; 95% CI -1.73 to 4.50) or disability (regression coefficient 1.27; 95% CI -1.39 to 3.64). For the other covariates, there was also no clinically significant influence on the treatment effects.

Conclusion

There is no influence of allocation concealment or ITT analysis on treatment effects of physical therapy interventions for pain and disability in LBP trials.

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The Effect of Timing of Physical Therapy for Acute Low Back Pain on Health Services Utilization: A Systematic Review

Publication date: July 2019

Source: Archives of Physical Medicine and Rehabilitation, Volume 100, Issue 7

Author(s): Elizabeth Arnold, Janna La Barrie, Lisley DaSilva, Meagan Patti, Adam Goode, Derek Clewley

Abstract

Objective

To synthesize literature about the effect of early physical therapy (PT) for acute low back pain (LBP) on subsequent health services utilization (HSU), compared to delayed PT or usual care.

Data Sources

Electronic databases (MEDLINE, CINAHL, Embase) were searched from their inception to May 2018.

Study Selection

Study selection included randomized control trials and prospective and retrospective cohort studies that investigated the association between early PT and HSU compared to delayed PT or usual care. Two independent authors screened titles, abstracts, and full-text articles for inclusion based on eligibility criteria, and a third author resolved discrepancies. Eleven out of 1146 articles were included.

Data Extraction

Two independent reviewers extracted data on participants, timing of PT, comparisons to delayed PT or usual care, and downstream HSU, and a third reviewer assessed the information to ensure accuracy and reach consensus. Risk of bias was assessed with the Downs and Black checklist using the same method.

Data Synthesis

Eleven studies met eligibility criteria. Early PT is within 30 days of the index visit for acute LBP. Five out of 6 studies that compared early PT to delayed PT found that early PT reduces future HSU. Random effects meta-analysis indicated a significant reduction in opioid use, spine injection, and spine surgery. Five studies compared early PT to usual care and reported mixed results.

Conclusions

Early PT for acute LBP may reduce HSU, cost, and opioid use, and improve health care efficiency. This review may assist patients, health care providers, health care systems, and third-party payers in making decisions for the treatment of acute LBP.

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The Central Sensitization Inventory predict pain‐related disability for musculoskeletal disorders in the primary care setting

Abstract

Background

Central sensitization (CS) is found in patients with musculoskeletal disorders and is related to clinical symptoms, including pain‐related disability. The Central Sensitization Inventory (CSI) has been developed for patients who are at risk of symptoms related to CS, and CSI severity levels are suggested for clinical interpretation of the CSI score. However, the longitudinal relationship between CSI severity and pain‐related disability is unclear in primary care. In this study, we investigated the association between CSI severity levels and the profiles of patients with musculoskeletal disorders as well as the longitudinal relationship between CSI severity levels and pain‐related disability in primary care settings.

Methods

A total of 553 patients were assessed using CSI, EuroQol‐5 dimension (EQ5D), and Brief Pain Inventory (BPI). Of the 553 patients, 150 patients were reassessed at the 3‐month follow‐up. Patients were grouped into three severity levels according to baseline CSI score: subclinical, mild, and moderate to higher level.

Results

As the CSI severity levels increased, the clinical symptoms tended to worsen on cross‐sectional analysis (p<0.05). Pain‐related disability at the 3‐month follow‐up was significantly higher for patients with moderate to high baseline CSI severity levels than for patients with subclinical baseline CSI levels (p<0.001). Furthermore, pain‐related disability increased according to the CSI severity level, with a medium to large effect size. However, there were no differences in pain duration across the CSI severity levels.

Conclusions

CSI has clinical utility as a prediction tool regardless of pain duration in patients with musculoskeletal disorders in primary care settings.

This article is protected by copyright. All rights reserved.

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Pain vs. comfort diary: A fully remote app‐based experiment

Abstract

Background

Focusing on pain while completing a pain diary might have detrimental effects on pain intensity. Inverted comfort ratings might be used instead.

Methods

A fully remote app‐based registered experiment was conducted to investigate the effects of a pain vs. comfort diary on 7‐day recall ratings of pain intensity during a three‐week period. The diary included questions about past, current and expected pain or comfort. Randomization took place by the study app, thereby controlling for effects of experimenter bias.

Results

Contrary to the study hypothesis, multilevel regression showed a more pronounced decrease in 7‐day recall ratings of pain in the group who rated pain intensity daily (N = 184) than in the group who rated comfort daily (N = 205, B = ‐0.17, p = 0.034). There were no between‐group differences in secondary outcomes (comfort, depressive symptoms, pain interference, and happiness). Exploratory analyses revealed more pronounced decreases in pain intensity in participants who experienced less frequent pain in the previous six months. Correlations between pain and comfort ratings decreased from ‐0.39 at baseline to ‐0.06 after three weeks.

Conclusions

The findings do not support the potential beneficial effects of replacing diary ratings of pain intensity with diary ratings of comfort. The unexpected decreases among those who completed daily pain diaries might have been due to the inclusion of questions about expected pain. Decreasing correlations between pain and comfort ratings suggest that comfort ratings are not merely inverted pain ratings; rather, they appear to assess a domain distinct from pain intensity.

This article is protected by copyright. All rights reserved.

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Ziconotide for spinal cord injury related pain

Abstract

Background

Central neuropathic pain related to spinal cord injury is notoriously difficult to treat. So far most pharmacological and surgical options have shown but poor results. Recently ziconotide has been approved for use both neuropathic and non‐neuropathic pain. In this cohort study, we assessed responder rate and long term efficacy of intrathecal ziconotide in patients with pain related to spinal cord injury.

Methods

Patients presenting chronic neuropathic related to spina cord lesions that was refractory to medical pain management were considered for inclusion. Those accepting were tested by lumbar puncture injection of ziconotide or continuous intrathecal infusion and if a significant decrease in pain scores (>40%) was noted they were implanted with a continuous infusion pump. They were then followed up for at least one year with constant assessment of the evolution of pain and side effects.

Results

Out of the twenty patients tested fourteen had a decrease in pain scores of more than 40% but only eleven (55%) were implanted with permanent pumps due to side effects and patient choice. These were followed up on average for 3.59 years (±1.94) and in eight patients an above threshold decrease in pain scores was maintained. Overall in patients that responded to the test baseline VAS was 7.91 and 4.31 at last follow up with an average dose of 7.2µg of ziconotide per day. Six patients (30%) did not respond to any test and in three patients side effects precluded pump implantation. No significant long term effects of the molecule were noted.

Conclusion

This study shows response to intrathecal ziconotide test in 40% of the patients of a very specific population in whom other therapeutic options are not available. This data justifies the development further studies such as a long term randomized controlled trial.

This article is protected by copyright. All rights reserved.

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Effect of psychomotricity in combination with 3 months of active shoulder exercises in patients with chronic shoulder pain: Primary results from an investigator-blinded, randomised, controlled trial

Publication date: Available online 24 June 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Kim Gordon Ingwersen, Jette Wessel Vobbe, Lise Lang Pedersen, Lilli Sørensen, Niels Wedderkopp

Abstract

Objective

To evaluate whether psychomotor therapy (PMT) in combination with usual care active exercise rehabilitation for the shoulder (AE) is superior to merely AE.

Design

The trial was a single-centre, stratified (by corticosteroid injection [yes/no]), randomised and controlled superiority trial.

Setting

Shoulder unit of the orthopaedic department at Hospital Lillebaelt – Vejle Hosiptal

Participants

Eligible participants were adults aged 18–75 years with shoulder complaints lasting for at least three months, in addition to a score equal to or below three on the Multidimensional Assessment of Interceptive Awareness (MAIA) score. Furthermore, patients had at least VAS-pain= 2 in rest; 3 at night and 5 in activity (range: 0–10).

Interventions

Patients were randomised to 12 weeks of AE (control group) or in combination with five PMT sessions (Intervention group).

Main Outcome Measure

Primary outcome was the patient reported outcome score “Disability of the Arm, Shoulder and Hand (DASH) questionnaire”. Primary endpoint was 12 weeks after baseline.

Results

There was no between group difference in function between the intervention group and control group.

Conclusion

Our results showed no additional benefit on patient reported function and pain from PMT over ususal care in patients with long-lasting shoulder pain and low body awareness. This finding suggests that PMT add no additional benefit to patients’ recovery in relation to pain and active function in comparison to standard care.

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The relation between parental chronic pain and pain‐related attention and interpretation biases in pain‐free adolescents

Abstract

Background

Children of chronic pain patients run greater risk for developing chronic pain themselves. Exposure to chronic pain of the parent might install cognitive (e.g., pain catastrophizing, interpretation and attentional bias) and affective (e.g., pain anxiety) vulnerability which increase the risk for the development of chronic pain complaints in offspring. This study examines whether pain‐free offspring of parents with chronic pain complaints make more health‐threatening interpretations and display a stronger pain‐related attentional bias compared to the offspring of pain‐free parents. We furthermore examined differences between both groups on pain catastrophizing, pain anxiety, and somatic symptoms, and explored the relations between parental pain catastrophizing and aforementioned pain vulnerability measures in offspring.

Methods

Offspring of parents with chronic pain complaints (n=24) and pain‐free parents (n=27) completed measures of attentional bias (i.e., pictorial dot probe), interpretation bias (i.e., ambiguous word association task), pain catastrophizing, pain anxiety, and somatic symptoms. Parents completed measures of pain catastrophizing and psychological distress.

Results

No differences between offspring of parents with and without pain complaints were observed on pain catastrophizing, pain anxiety, and somatic symptoms. Both groups of healthy adolescents predominantly showed benign, non‐health‐threatening interpretations. Children of pain‐free parents showed an attention bias for pain stimuli, while offspring of parents with pain complaints showed no such bias.

Conclusions

Future research is needed to further elucidate the precise role of parental pain in the development of pain‐related biases and the significance of these biases in the onset and/or maintenance of a chronic pain condition in children and adolescents.

This article is protected by copyright. All rights reserved.

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Psychological pain responses in athletes and non‐athletes with low back pain: avoidance and endurance matter

Abstract

Background

Dysfunctional psychological pain responses, namely fear‐avoidance (FAR), including catastrophizing and helplessness, as well as endurance‐related responses (ER), including thought suppression and overactivity have been shown to be risk factors for persistent low back pain (LBP). Literature suggests that athletes may differ from non‐athletes regarding psychological responses to pain.

Objectives

This study set out to compare FAR and ER between athletes and non‐athletes with LBP. It was hypothesized that athletes would report less frequent FAR and more frequent ER, and that both FAR and ER are associated with LBP intensity and disability.

Methods

173 athletes and 93 non‐athletes cross‐sectionally reported how frequently they employ FAR and ER on the Avoidance‐Endurance Questionnaire (AEQ), as well as LBP intensity and disability on the Chronic Pain Grad Questionnaire (CPGS). MANOVA was applied to compare FAR and ER between athletes and non‐athletes. Hierarchical multiple linear regression models were used to determine the unique associations between FAR and ER with LBP intensity and disability.

Results

Athletes reported lower frequencies of behavioural avoidance than non‐athletes, but no other FAR variables differed between the groups. Frequencies of ER did not differ between athletes and non‐athletes. Regression analysis indicated substantial associations of FAR with LBP intensity, as well as of FAR and ER with disability in athletes and non‐athletes.

Conclusions

The results of the present study suggest that athletes and non‐athletes with LBP differ regarding behavioural avoidance, but overall, differences regarding pain responses are marginal. FAR and ER are both reported in athletes and non‐athletes and contribute to disability in both groups.

This article is protected by copyright. All rights reserved.

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An unstable lump in the groin

A 49 year old man with type 2 diabetes presented with a three day history of severe right sided groin swelling and pain, feeling generally unwell, fatigue, and fever. His medical history included two...

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Identifying Plasma Derived Extracellular Vesicle (EV) Contained Biomarkers in the Development of Chronic Neuropathic Pain

This article describes the DE miRNA content of plasma derived EVs, comparing neuropathic pain to normal conditions. This data indicates that EV miRNAs may be important in nociception and may also serve as biomarkers for chronic pain. These results encourage further research on EV miRNAs in chronic neuropathic pain sufferers.

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Abstracts of low back pain trials are poorly reported, contain spin of information and are inconsistent with the full text: An overview study

Publication date: Available online 14 June 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Dafne Port Nascimento, Leonardo Oliveira Pena Costa, Gabrielle Zoldan Gonzalez, Christopher G. Maher, Anne M. Moseley

Abstract

Objective

To investigate trials abstracts evaluating treatments for low back pain with regards to completeness of reporting, spin (i.e., interpretation of study results that overemphasizes the beneficial effects of the intervention), and inconsistencies in data with the full text.

Data sources

The search was performed on Physiotherapy Evidence Database (PEDro) in February 2016.

Study Selection

This is an overview study of a random sample of 200 low back pain trials published between 2010 and 2015. The languages of publication were restricted to English, Spanish and Portuguese.

Data Extraction

Completeness of reporting was assessed using the CONSORT for Abstracts checklist (CONSORT-A). Spin was assessed using a SPIN-checklist. Consistency between abstract and full text were assessed by applying the assessment tools to both the abstract and full text of each trial and calculating inconsistencies in the summary score (paired t test) and agreement in the classification of each item (Kappa statistics). Methodological quality was analyzed using the total PEDro score.

Data Synthesis

The mean number of fully reported items for abstracts using the CONSORT-A was 5.1 (SD 2.4) out of 15 points and the mean number of items with spin was 4.9 (SD 2.6) out of 7 points. Abstract and full text scores were statistically inconsistent (P=0.01). There was slight to moderate agreement between items of the CONSORT-A in the abstracts and full text (mean Kappa 0.20 SD 0.13) and fair to moderate agreement for items of the SPIN-checklist (mean Kappa 0.47 SD 0.09).

Conclusions

The abstracts were incomplete, with spin and inconsistent with the full text. We advise health care professionals to avoid making clinical decisions based solely upon abstracts. Journal editors, reviewers and authors are jointly responsible for improving abstracts, which could be guided by amended editorial policies.

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Weight management and musculoskeletal pain: Does sleep mediate the connection?

Abstract

In a recent issue of the European Journal of Pain, Dunlevy et al. (2019) presented the results of a retrospective study using data from a weight management program. We would like to congratulate the authors on this important investigation which showed that weight loss of ≥5% reduced musculoskeletal (MSK) pain, specifically knee pain and low back pain, in patients with severe obesity.

This article is protected by copyright. All rights reserved.

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Associations between pain thresholds for heat, cold and pressure, and Pain Sensitivity Questionnaire (PSQ) scores in healthy women and in women with persistent pelvic pain

Abstract

Background

The Pain Sensitivity Questionnaire (PSQ) is a self‐rating instrument developed as a time‐ and cost‐saving alternative to quantitative sensory testing (QST). The aims of the study were to assess 1) the associations between PSQ scores and QST in women with persistent pelvic pain and in pain‐free controls, and 2) to what extent demographic variables and psychological distress influenced PSQ scores.

Methods

Fifty‐five healthy women and 37 women with persistent pelvic pain participated. All filled in the PSQ and Hospital Anxiety and Depression Scale and had QST (heat, cold, and pressure pain thresholds) performed on six locations on the body. Information on age, body mass index, smoking habits, and pain duration were collected. Principal component analysis and orthogonal partial least square regressions were used.

Results

The patients scored significantly higher on PSQ than the controls. Significant multivariate correlations between pain thresholds and PSQ scores were found only in the patient group. In the patient group, the heat and cold pain thresholds correlated more strongly with PSQ scores than the pressure pain threshold.

Conclusions

The PSQ score was significantly higher in pelvic pain patients, and correlations between QSTs and the PSQ were only found for patients.

This article is protected by copyright. All rights reserved.

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Masseter corticomotor excitability is decreased after intramuscular administration of nerve growth factor

Abstract

Background

Quantification of motor‐evoked potentials (MEPs) can contribute to better elucidate the central modulation of motor pathways in response to nociceptive inputs. The primary aim of this study was to assess the modulatory effects of nerve growth factor (NGF) injection on masseter corticomotor excitability.

Methods

The healthy participants of this randomized, double blind placebo‐controlled experiment were assigned to have injected into the right masseter muscle either NGF (n=25) or isotonic saline (IS, n=17). The following variables were assessed at baseline and 48 hours after the injection: right masseter MEP amplitude and corticomotor mapping and clinical assessment of jaw pain intensity and function. Repeated Measures ANOVA was applied to the data.

Results

NGF caused jaw pain and increased jaw functional disability after the injection (p<0.050). Also, the participants in the NGF group decreased the MEP amplitude (p<0.001) but the IS group did not present any significant modulation after the injection (p>0.050). Likewise, the participants in the NGF group reduced corticomotor map area and volume (p<0.001), but the IS group did not show any significant corticomotor mapping changes after the injection (p>0.050). Finally, there was a significant correlation between the magnitude of decreased corticomotor excitability and jaw pain intensity on chewing 48 hours after the NGF injection (r=‐0.51, p=0.009).

Conclusion

NGF‐induced masseter muscle soreness can significantly reduce jaw muscle corticomotor excitability, which in turn is associated with lower jaw pain intensity and substantiates the occurrence of central changes that most likely aim to protect the musculoskeletal orofacial structures.

This article is protected by copyright. All rights reserved.

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Corticomotor depression is associated with higher pain severity in the transition to sustained pain: a longitudinal exploratory study of individual differences

The organisation and function of the primary motor cortex is altered in the acute,6 transitional28 and chronic stages of musculoskeletal pain and in chronic pain populations, altered motor cortex plasticity is associated with pain severity and impaired function.29,30,40 These findings suggest that aberrant motor cortex plasticity may contribute to the development of chronic pain. However, direct evidence for a relationship between an individual's motor plasticity in response to pain and symptom severity is lacking.

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Comment on the paper “Cognitive Functional Therapy in patients with Non Specific Chronic Low Back Pain”, by Vibe Fersum et al

Abstract

We would like to thank the authors for publishing this article (Vibe Fersum et al., 2019). The approach called CFT is very promising and has caught the attention and interest of a huge number of clinicians in the management of non‐specific disabling chronic low back pain. We wholeheartedly agree that it is necessary to publish the results of the long term follow up even in circumstances where there may be a high risk of bias. Notably, the 1‐year follow‐up study of Vibe Fersum et al. (2013) already presented a number of methodological shortcomings, such as lack of clear information regarding blinding of assessors.

This article is protected by copyright. All rights reserved.

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A Novel Mu-Delta Opioid Agonist Demonstrates Enhanced Efficacy with Reduced Tolerance and Dependence in Mouse Neuropathic Pain Models

Pharmacological studies over the past few decades have demonstrated physiological interactions between the mu opioid receptor (MOR) and delta opioid receptor (DOR) systems. Inhibition of the DOR by various means had the effect of reducing MOR-mediated side effects like tolerance and dependence.1,44,51 Numerous other studies have shown altered activity of MOR- and DOR-selective ligands when the reciprocal receptor is inhibited.29,35 It is thus clear that the MOR and DOR systems extensively modulate each other, but the mechanisms are not known.

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Predicting Opioid Use, Increased Health Care Utilization and High Costs for Musculoskeletal Pain: What Factors Mediate Pain Intensity and Disability?

Best practice management of musculoskeletal pain is changing rapidly in response to recent health care reform initiatives. First and broadly in health care, value-based purchasing has incentivized high quality, low cost care.4,7 As a result, health care utilization and costs have become important outcomes by which health care systems and payers measure treatment effectiveness. Second and specific to management of musculoskeletal pain, recent clinical practice guidelines and national pain research priorities have called for reductions in opioid use, with the goal of increasing non-pharmacological treatment options while decreasing opioid-related morbidity and mortality.

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