Alterations in SUMOylation of the hyperpolarization‐activated cyclic nucleotide gated ion channel 2 during persistent inflammation

Abstract

Background

Unilateral injection of Complete Freund's Adjuvant (CFA) into the intra‐plantar surface of the rodent hindpaw elicits chronic inflammation and hyperalgesia in the ipsilateral hindlimb. Mechanisms contributing to this hyperalgesia may act over multiple time courses and can include changes in ion channel expression and post‐translational SUMOylation. Hyperpolarization‐activated, cyclic nucleotide‐gated (HCN) channels mediate the hyperpolarization‐activated current, I_h. An HCN2‐mediated increase in C‐nociceptor I_h contributes to mechanical hyperalgesia in the CFA model of inflammatory pain. Changes in HCN2 post‐translational SUMOylation and protein expression have not been systematically documented for a given DRG throughout the time course of inflammation.

Methods

This study examined HCN2 protein expression and post‐translational SUMOylation in a rat model of CFA‐induced hindpaw inflammation. L5 DRG cryosections were used in immunohistochemistry experiments and proximity ligation assays to investigate HCN2 expression and SUMOylation, respectively, on days 1 and 3 post‐CFA.

Results

Unilateral CFA injection elicited a significant bilateral increase in HCN2 staining intensity in small diameter DRG neurons on day 1 post‐CFA, and a significant bilateral increase in the number of small neurons expressing HCN2 but not staining intensity on day 3 post‐CFA. HCN2 channels were hyper‐SUMOylated in small diameter neurons of ipsilateral relative to contralateral DRG on days 1 and 3 post‐CFA.

Conclusions

Unilateral CFA injection elicits unilateral mechanical hyperalgesia, a bilateral increase in HCN2 expression and a unilateral increase in post‐translational SUMOylation. This suggests that enhanced HCN2 expression in L5 DRG is not sufficient for mechanical hyperalgesia in the early stages of inflammation and that hyper‐SUMOylation of HCN2 channels may also be necessary.

Significance

Nociceptor HCN2 channels mediate an increase in I_h that is necessary for mechanical hyperalgesia in a CFA model of chronic pain, but the mechanisms producing the increase in nociceptor I_h have not been resolved. The data presented here suggest that the increase in I_h during the early stages of inflammation may be mediated by an increase in HCN2 protein expression and post‐translational SUMOylation.

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The Pharmacokinetics, Efficacy, and Safety of a Novel Selective‐Dose Cannabis Inhaler in Patients with Chronic Pain: A Randomized, Double‐Blinded, Placebo‐Controlled Trial

Abstract

Background

Precise cannabis treatment dosing remains a major challenge, leading to physicians’ reluctance to prescribe medical cannabis.

Objective

To test the pharmacokinetics, analgesic effect, cognitive performance, and safety effects of an innovative medical device that enables the delivery of inhaled therapeutic doses of Δ⁹‐Tetrahydrocannabinol (THC) in patients with chronic pain.

Methods

In a randomized, 3‐arms, double‐blinded, placebo‐controlled, cross‐over trial, 27 patients received a single inhalation of Δ⁹‐THC: 0.5mg, 1mg, or a placebo.

Δ⁹‐THC plasma levels were measured at baseline and up to 150‐minutes post‐inhalation. Pain intensity and safety parameters were recorded on a 10‐cm visual analogue scale (VAS) at pre‐defined time points. Cognitive performance was evaluated using the selective sub‐tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB).

Results

Following inhalation of 0.5mg or 1mg, Δ⁹‐THC plasma C_max±SD were 14.3±7.7 and 33.8±25.7 ng/ml. T_max±SD were 3.7±1.4 and 4.4±2.1 minutes, and AUC₀→_infinity±SD were 300±144 and 769±331 ng*min/ml respectively. Both doses, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150‐minutes. The 1mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance.

Conclusion

This feasibility trial demonstrated that a metered‐dose cannabis inhaler delivered precise and low THC doses, produced a dose‐dependent and safe analgesic effect in patients with neuropathic pain/ complex‐regional pain syndrome (CRPS). Thus, it enables individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically by accepted pharmaceutical models.

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[Clinical Picture] Alternative causes of ankle pain in a patient with enthesopathy and X-linked hypophosphataemia

A 43-year-old Australian-born, white man was referred to our unit because of increasing pain in both his ankles. The pain had developed approximately 7 days earlier. 3 days before the pain started, he had been admitted to hospital with cellulitis of his upper arm; he had been treated for septicaemia and acute kidney injury caused by an infection with Streptococcus pyogenes.

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My body is not working right: a cognitive behavioral model of body image and chronic pain

No abstract available

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Placebo effect in children: the role of expectation and learning

Classical conditioning and expectations are well-known underlying mechanisms of placebo hypoalgesia. Only little is known about their differential effect in adults, however, and even less in children. Previous studies in children evoked placebo hypoalgesia either with expectations alone or in combination with classical conditioning and revealed conflicting results. Furthermore, these studies investigated children of different ages making it even more difficult to draw conclusions. This study tried to disentangle classical conditioning and expectations by investigating them separately. To examine age effects, n = 172 children (6-9, 10-13, and 14-17 years) as well as n = 32 adults (> = 18 years) were tested using a heat pain paradigm investigating the effectiveness of creams some of which were bogusly introduced as analgesic. In addition to subjective pain intensity ratings, peripheral physiological measures were recorded. Results showed a successful induction of placebo hypoalgesia by both mechanisms for pain ratings and heart rate acceleration. Placebo hypoalgesia was particularly pronounced in children younger than 14 years. Furthermore, placebo hypoalgesia was more marked in children whose mothers raised the expectations. It was also stronger in participants who noticed a strong pain reduction during learning trials. These results encourage the use of placebo effect in clinical practice, particularly for younger children. They underline the relevance of an initial pain reduction and encourage the inclusion of parents in treatment.

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Intergroup anxiety in pain care: impact on treatment recommendations made by white providers for black patients

Race disparities in pain care are well-documented. Given that most black patients are treated by white providers, patient–provider racial discordance is one hypothesized contributor to these disparities. Research and theory suggest that providers' trait-level intergroup anxiety impacts their state-level comfort while treating patients, which, in turn, impacts their pain treatment decisions. To test these hypothesized relationships, we conducted a planned secondary analysis of data from a randomized controlled trial of a perspective-taking intervention to reduce pain treatment disparities. Mediation analyses were conducted on treatment decision data from white providers for black virtual patients with chronic pain. Results indicated that white providers with higher trait-level intergroup anxiety reported lower state-level comfort treating black patients and were thereby more likely to recommend opioid (indirect effect = 0.76, 95% confidence interval [CI]: 0.21-1.51) and pain specialty (indirect effect = 0.91, 95% CI: 0.26-1.78) treatments and less likely to recommend nonopioid analgesics (indirect effect = −0.45, 95% CI: −0.94 to −0.12). Neither trait-level intergroup anxiety nor state-level comfort significantly influenced provider decisions for physical therapy. This study provides important new information about intrapersonal and interpersonal contributors to race disparities in chronic pain care. These findings suggest that intergroup anxiety and the resulting situational discomfort encroach on the clinical decision-making process by influencing white providers' decisions about which pain treatments to recommend to black patients. Should these findings be replicated in future studies, they would support interventions to help providers become more aware of their trait-level intergroup anxiety and manage their state-level reactions to patients who are racially/ethnically different from themselves.

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Receipt of multiple outpatient opioid prescriptions is associated with increased risk of adverse outcomes in youth: opioid prescribing trends, individual characteristics, and outcomes from 2005 to 2016

Data on all outpatient opioid prescriptions (N = 71,647) to youth below age 21 (N = 42,020) from 2005 to 2016 were extracted from electronic medical records within a university hospital system in New Mexico (NM) as were demographic details and markers of morbidity/mortality. Relative risk was calculated for markers of morbidity/mortality based on sociodemographic characteristics. The sample was primarily male (55.0%), Hispanic/Latinx (50.1%), English-speaking (88.9%), and publicly insured (50.1%). Mean age was 13.54 (SD = 6.50). From 2005 to 2016, overall frequency of opioid prescriptions increased by 86.6% (from 2470 to 4610) with the largest increase (206.2%) observed from 2005 to 2008 (2470-7562). Patients who were older, white, and non-Hispanic were more likely to receive multiple opioid prescriptions. Large relative increases in morbidity and mortality were documented, although base rates remained low. The percentage of individuals within the sample who experienced an overdose increased steadily from 0 in 2005 to 1.09% in 2016. Incidence of mortality increased from 0.12% of the sample to 1.39% in 2016. The proportion of individuals who received a medication for the treatment of opioid dependence increased from 0.06% in 2005 to 0.44% in 2016. Significantly increased risk of adverse outcomes was observed in patients receiving multiple opioid prescriptions, and in patients who were older, of minority race, received their first prescription in an outpatient clinic, and publicly insured or uninsured. Results add to the growing literature concerning opioid prescription rates over time. They also provide important information on potential additive risks of adverse outcomes when pediatric patients receive multiple opioid prescriptions.

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Nonsurgical mouse model of endometriosis-associated pain that responds to clinically active drugs

Endometriosis is an estrogen-dependent inflammatory disease that affects approximately 10% of women. Debilitating pelvic or abdominal pain is one of its major clinical features. Current animal models of endometriosis-associated pain require surgery either to implant tissue or to remove the ovaries. Moreover, existing models do not induce spontaneous pain, which is the primary symptom of patients with chronic pain, including endometriosis. A lack of models that accurately recapitulate the disease phenotype must contribute to the high failure rate of clinical trials for analgesic drugs directed at chronic pain, including those for endometriosis. We set out to establish a murine model of endometriosis-associated pain. Endometriosis was induced nonsurgically by injecting a dissociated uterine horn into a recipient mouse. The induced lesions exhibited histological features that resemble human lesions along with an increase in proinflammatory cytokines and recruitment of immune cells. We also observed the presence of calcitonin gene–related peptide–, TRPA1-, and TRPV1-expressing nerve fibers in the lesions. This model induced mechanical allodynia, spontaneous abdominal pain, and changes in thermal selection behavior that indicate discomfort. These behavioral changes were reduced by drugs used clinically for endometriosis, specifically letrozole (aromatase inhibitor) and danazol (androgen). Endometriosis also induced neuronal changes as evidenced by activation of the NF-κB signaling pathway in TRPA1- and TRPV1-expressing dorsal root ganglion neurons. In conclusion, we have established a model of endometriosis-associated pain that responds to clinically active drugs and can, therefore, be used to identify novel therapies.

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Pharmacological characterization of a rat Nav1.7 loss-of-function model with insensitivity to pain

Sodium channel Nav1.7, encoded by the SCN9A gene, is a well-validated target that plays a key role in controlling pain sensation. Loss-of-function mutations of Nav1.7 can cause a syndrome of profound congenital insensitivity to pain in humans. Better understanding of how the loss of Nav1.7 leads to loss of pain sensibility would help to decipher the fundamental mechanisms of nociception and inform strategies for development of novel analgesics. Using a recently described rat Nav1.7 loss-of-function model with deficient nociception but intact olfactory function, we investigated the involvement of endogenous opioid and cannabinoid systems in this rodent model of Nav1.7-related congenital insensitivity to pain. We found that both the opioid receptor antagonist naloxone and cannabinoid receptor blockers SR141716A (rimonabant) and SR144528 fail to restore acute pain sensitivity in Nav1.7 loss-of-function rats. We observed, however, that after rimonabant administration, Nav1.7 loss-of-function but not WT rats displayed abnormal behaviours, such as enhanced scratching, caudal self-biting, and altered facial expressions; the underlying mechanism is still unclear. Dorsal root ganglion neurons from Nav1.7 loss-of-function rats, although hypoexcitable compared with WT neurons, were still able to generate action potentials in response to noxious heat and capsaicin. Our data indicate that complete loss of dorsal root ganglion neuron excitability is not required for insensitivity to pain and suggest that endogenous opioid and cannabinoid systems are not required for insensitivity to pain in the absence of Nav1.7 channels in this rat Nav1.7 loss-of-function model.

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Low-dose interleukin-2 reverses behavioral sensitization in multiple mouse models of headache disorders

Headache disorders are highly prevalent and debilitating, with limited treatment options. Previous studies indicate that many proinflammatory immune cells contribute to headache pathophysiology. Given the well-recognized role of regulatory T (Treg) cells in maintaining immune homeostasis, we hypothesized that enhancing Treg function may be effective to treat multiple headache disorders. In a mouse model of chronic migraine, we observed that repeated nitroglycerin (NTG, a reliable trigger of migraine in patients) administration doubled the number of CD3+ T cells in the trigeminal ganglia without altering the number of Treg cells, suggesting a deficiency in Treg-mediated immune homeostasis. We treated mice with low-dose interleukin-2 (ld-IL2) to preferentially expand and activate endogenous Treg cells. This not only prevented the development of NTG-induced persistent sensitization but also completely reversed the established facial skin hypersensitivity resulting from repeated NTG administration. The effect of ld-IL2 was independent of mouse sex and/or strain. Importantly, ld-IL2 treatment did not alter basal nociceptive responses, and repeated usage did not induce tolerance. The therapeutic effect of ld-IL2 was abolished by Treg depletion and was recapitulated by Treg adoptive transfer. Furthermore, treating mice with ld-IL2 1 to 7 days after mild traumatic brain injury effectively prevented as well as reversed the development of behaviors related to acute and chronic post-traumatic headache. In a model of medication overuse headache, Ld-IL2 completely reversed the cutaneous hypersensitivity induced by repeated administration of sumatriptan. Collectively, this study identifies ld-IL2 as a promising prophylactic for multiple headache disorders with a mechanism distinct from the existing treatment options.

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Discrete and dynamic postoperative pain catastrophizing trajectories across 6 months: A prospective observational study

Publication date: Available online 21 May 2020

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Nicholas A. Giordano, Alexandra Kane, Kalyn C. Jannace, Winifred Rojas, Mary Jo Lindl, Eugenio Lujan, Harold Gelfand, Michael L. Kent, Krista B. Highland

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Interplay between body schema, visuospatial perception and pain in patients with spinal cord injury

Abstract

Background

Changes in body representations (body image and/or body schema) have been reported in several chronic musculoskeletal pain syndromes, but rarely in patients with neuropathic pain and never in patients with spinal cord injury (SCI)‐related pain.

Methods

We used implicit motor imagery (the laterality judgement task, and visuospatial body perception tests) in 56 patients with thoracic SCI with (n = 32) or without (n = 24) pain below the level of the injury, and in a group of matched healthy controls (n = 37). We compared the participants' reaction time and the accuracy with which they identified the laterality of hands and feet presented in various orientations. Visuospatial body perception was assessed with a series of tests referred to as the 'horizontal subjective body midline', and the umbilicus‐reaching task, in which participants were asked to estimate the location of the umbilicus under different experimental conditions.

Results

Both groups of patients had longer reaction times for the identification of laterality for the feet than for the hands, but with no difference in accuracy. This longer reaction time was not correlated with spinal lesion severity, but was directly related to both average pain intensity and specific neuropathic pain components. The umbilicus‐reaching task was affected in both groups of patients, with no effect of pain intensity. By contrast, the horizontal subjective body midline task was unaffected.

Conclusion

These results suggest an interplay between lower body scheme distorsions and pain in patients with spinal cord injury.

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Comparison of the Effects of Vapocoolant Spray and Topical Anesthetic Cream on Pain during Intraarticular Injection of the Shoulder: a Randomized Double-Blind Controlled Trial

Publication date: Available online 20 May 2020

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Young-Eun Moon, Sang-Hyun Kim, Hyun Seok, Seung Yeol Lee

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Headache attributed to craniocervical dystonia: a prospective cohort study

Abstract

Background

Cervical dystonia is the most common form of focal idiopathic dystonia and is frequently associated with pain. Headaches are not considered to be more prevalent amongst patients presenting with cervical dystonia, and headaches attributed to craniocervical dystonia are considered to be a rare disorder, despite the lack of studies and clinical information regarding the subject.

Objectives

To investigate the prevalence, characteristics, and impact of headaches attributed to craniocervical dystonia in cervical dystonia patients receiving treatment with botulinum toxin type‐A (BoT‐A).

Methods

Twenty‐four patients presenting with cervical dystonia were assessedbefore receiving their scheduled BoNT‐A injections and then again approximately four and sixteen weeks after, regarding the clinical characteristics of their dystonia and headaches. Headaches were classified in accordance with the current International Classification of Headache Disorders. We used the Short Form‐36 Health Survey, Hospital Anxiety and Depression Scale, Headache Impact Test‐6, Toronto Western Spasmodic Torticollis Rating Scale and McGill Pain Questionnaire.

Results

Nineteen patients (79.1%) presented with cervical dystonia associated with pain and 18 (75.0%) with headaches. The prevalence of headaches attributed to craniocervical dystonia was 29.2%; HIT‐6: 60.1 ± 9.9. Patients with headaches presented significantly poorer TWSTRS pain scores, compared to patients with no headaches. Those with headaches attributed to craniocervical dystonia presented with more disability and demonstrated a significant improvement in the impact of headaches after BoNT‐A injections, together with an improvement in the dystonia.

Conclusions

Headaches are highly prevalent amongst cervical dystonia patients, have an impact on their quality of life and improves after BoNT‐A injections.

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A hidden mesencephalic variant of central pain

Abstract

Background

Central post‐stroke pain (CPSP) can arise after lesions anywhere in the central somatosensory pathways, essentially within the spinothalamic system (STS). Although the STS can be selectively injured in the mesencephalon, CPSP has not been described in pure midbrain infarcts.

Methods

Out of more than 300 CPSP consecutive cases, we describe five patients who developed definite neuropathic pain following lesions circumscribed to the postero‐lateral mesencephalon.

Results

The mesencephalic lesion responsible for pain was always haemorhagic and always involved the spinothalamic tract (STT), as demonstrated by suppressed laser‐evoked potentials in every case, with or without preserved lemniscal function. In 3 cases the midbrain injury could be ascribed to trauma, presumably from the cerebellar tentorium. Due to the paucity of sensory symptoms, the pain was considered as ‘psychogenic’ in two of the patients until electrophysiological testing confirmed STT involvement.

Conclusion

Postero‐lateral midbrain lesions should be added to potential causes of CPSP. Because pain and spinothalamic deficits may be the only clinical sign, and because small lateral midbrain lesions may be difficult to trail with MRI, mesencephalic CPSP can be misdiagnosed as malingering or psychogenic pain for years.

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Anesthesia analgesia in the amygdala

Nature Neuroscience, Published online: 18 May 2020; doi:10.1038/s41593-020-0645-3

General anesthetics during surgery are presumed to block pain by dampening brain activity and promoting loss-of-consciousness. A new study shows that anesthetics activate an endogenous analgesia neural ensemble in the central nucleus of the amygdala.

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General anesthetics activate a potent central pain-suppression circuit in the amygdala

Nature Neuroscience, Published online: 18 May 2020; doi:10.1038/s41593-020-0632-8

Hua and Chen et al. show that general anesthesia activates a distinct population of central amygdala neurons and that these neurons can potently suppress pain responses through their widespread projections to many pain-processing centers in the brain.

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Radiotherapy for pain relief from bone metastases during Coronavirus (COVID‐19) pandemic

Abstract

The worldwide pandemic of coronavirus disease (COVID‐19) has drammatically and rapidly spread in Italy the last month.

By now, nevertheless Italian government efforts to contain the outbreak with escalating restrictive measures, 205463 cases were confirmed, with 27967 deaths

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A systematic review of cross‐cultural validation of the pain catastrophizing scale

Abstract

Background

Although it has been suggested that the different cultural and social environments between countries contribute to variations in pain catastrophizing (PC), an international comparison of PC in patients with chronic pain has not yet been reported. Prior to undertaking this comparison, a cross‐cultural assessment of the pain catastrophizing scale (PCS) was undertaken to explore the different factor‐structures among each translated version of the PCS.

Methods

The protocol for this systematic review was prospectively registered on International Prospective Register of Systematic Reviews 2018 (CRD 42018086719). Electronic searches were conducted in the following databases: Ovid/Embase, Ovid/MEDLINE, and Ovid/PsycINFO, and then 19 articles (16 language versions) were included in this review. Based on the COSMIN check list, we investigated language translation followed by five‐domains of cross‐cultural validation: structural validity, internal consistency, test‐retest reliability, and hypotheses testing for construct validity in each study.

Results

We found that (1) there were inconsistent structural models among each translated version, leading to variant subdomain structures for rumination, magnification, and helplessness, (2) all languages versions showed sufficient internal consistency when assessing whole items, and (3) the correlation coefficients between pain intensities and total scores of the PCS among each sample of chronic pain varied across the studies.

Conclusions

These results indicate that the total score of the PCS could be compared across each translated version, however, caution is warranted when each subdomain of the PCS is compared between countries.

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The association of initial provider type on opioid fills for individuals with neck pain

Publication date: Available online 11 May 2020

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Christopher J. Louis, Carolina-Nicole S. Herrera, Brigid M. Garrity, Christine M. McDonough, Howard Cabral, Robert B. Saper, Lewis E. Kazis

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Severity of Preoperative Myelopathy Symptoms Affects Patient-reported Outcomes, Satisfaction, and Return to Work After Anterior Cervical Discectomy and Fusion for Degenerative Cervical Myelopathy

Study Design. Retrospective review of prospectively-collected registry data. Objective. To compare the patient-reported outcomes, satisfaction, and return to work among a large cohort of patients stratified by preoperative myelopathy severity undergoing Anterior Cervical Discectomy and Fusion (ACDF) for Degenerative Cervical Myelopathy. Summary of Background Data. Recent clinical practice guidelines noted a lack of studies stratifying their sample based on preoperative disease severity. The benefits of early surgical intervention for patients with mild myelopathy remain uncertain. Methods. A prospectively-maintained registry was retrospectively reviewed for all patients who underwent primary ACDF for Degenerative Cervical Myelopathy. Patients were stratified based on severity of preoperative myelopathy symptoms according to the Japanese Orthopaedic Association (JOA) scale: mild (>13), moderate (9–13), or severe (<9). Patients were prospectively followed for at least 2 years. Results. In total, 219 patients were included: 74 mild, 94 moderate, and 51 severe cases. The mild group had significantly better Neurogenic Symptoms (NS), Neck Disability Index (NDI), SF-36 Physical (PCS), and Mental Component Summary at baseline (P <� 0.05). Neck and arm pain scores were similar at all time points. At 2 years, the severe group still had significantly worse patient-reported outcomes and lower rates of satisfaction, expectation fulfilment and return to work. However, they had significantly greater improvement in JOA, Neurogenic Symptoms, NDI, PCS, and Mental Component Summary, and a larger proportion attained minimal clinically important difference (MCID) for NDI and PCS. All three groups had similar proportions attaining MCID for JOA. Conclusion. Patients with severe myelopathy experienced a greater improvement after ACDF. Although fewer patients attained MCID, early surgical intervention for patients with mild myelopathy should also be considered, as this may allow patients to maintain their higher functional status. They also had high rates of postoperative satisfaction and return to work. The clinical trajectory outlined in this study may provide valuable prognostic information for patients. Level of Evidence: 3

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Neurological Outcome and Complications in Patients With Surgically Treated Spinal Metastases

Study Design. Retrospective cohort. Objective. Evaluate the epidemiology of surgical patients with spinal metastases, identify the complications, and evaluate their neurological prognoses. Summary of Background Data. The development of new oncological treatments and screening tests have increased the survival of oncologic patients, and consequently, the incidence of metastatic lesions of the spine. Methods. Retrospective cohort of 40 patients surgically treated at the Hospital de Clínicas of UNICAMP for spinal metastases from January 2010 to September 2018, after diagnosis of symptomatic spinal cord compression and/or mechanical instability of the spine. Retrospectively analyzed patient charts applied the SINS score to evaluate the presence of mechanical instability. Neurological function was classified based on the Frankel index preoperative and postoperatively. To evaluate the association between variables, the Chi-square test, Fisher exact test, or Fisher–Freeman–Halton test was applied. For evaluating the improvement of neurological status between the Frankel scores before and after surgery, the McNemar test was applied for categorical and qualitative variables. In both the tests, variables with values of P > 0.05 were considered. Results. Pain as the reason for the first visit presented an odds ratio (OR) = 2.44 (95% [CI]: 1.14–5.2) for instrumentation need (P = 0.024). A higher SINS score corresponded to the indication for instrumentation surgery due to the instability of the spine (P = 0.004). Within 30 days postoperative, five patients (11.1%) had complications. There was a statistically significant neurological improvement in patients who underwent surgery (P = 0.002). Conclusion. Pain as the first symptom was related to mechanical instability of the spine and surgical instrumentation. Patients treated with surgery presented improvement of the neurological function in the postoperative period. Level of Evidence: 3

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Insomnia is a risk factor for spreading of chronic pain: A Swedish longitudinal population study (SwePain)

Abstract

Background

Recent evidence suggests that insomnia negatively influences the occurrence of generalized pain. This study examined whether insomnia is a risk factor for the transition from local pain to generalized pain (i.e., spreading of pain).

Methods

This longitudinal study, with a follow‐up of 24 months, included 959 participants (mean age: 55.8 years; SD: 13.9) with local or regional pain at baseline. Participants were grouped by insomnia symptoms as measured by the Insomnia Severity Index. Spreading of pain was measured by body manikins based on the spatial distribution of pain on the body. We defined two outcome categories; one with relatively localized pain (i.e., local pain and moderate regional pain ), and one with relatively generalized pain (i.e., substantial regional pain and widespread pain). Baseline age, sex, education, depressive symptoms, anxiety symptoms, catastrophizing, pain intensity, and spread of pain were also included in the Generalized Linear Model analysis.

Results

The unadjusted model showed that the risk of spreading of pain increased with an increase in insomnia symptoms (no insomnia: 55.4%; subthreshold insomnia: 25.4% moderate insomnia: 16.5% and severe insomnia: 2.7%). The risk increased in a dose‐dependent manner; moderate insomnia risk ratio (RR) 2.34 (95% confidence interval [CI]: 1.34 – 4.09) and severe insomnia RR 4.13 (95% CI: 1.56 – 10.92). The results were maintained in the fully adjusted model although moderate regional pain was the strongest predictor RR 6.95 (95% CI: 3.11‐15.54).

Conclusion

Our findings show a strong prospective relationship between insomnia symptoms and the transition from relatively localized to generalized pain.

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Beyond Pain Intensity and catastrophizing: The Association between Self‐Enhancing Humor Style and the Adaptation of Individuals with Chronic Pain

Abstract

Background

Many questions regarding the process by which self‐enhancing humor style has an effect on chronic pain individuals’ adjustment remain unanswered. The aim of the present study was to analyse the association of self‐enhancing humor style with adjustment in a sample of individuals with chronic pain, over and above the role of catastrophizing and pain intensity. Adjustment was assessed using measures of depression, pain interference, and flourishing. We also examined the indirect association between self‐enhancing humor style and adjustment via pain acceptance. Methods: The study included 427 patients with heterogeneous chronic pain conditions. The study hypotheses were tested using three multiple linear regression analyses, one for each of the criterion variables.

Results

Consistent with the study hypothesis, both direct and indirect associations were found between self‐enhancing humor style and depressive symptoms, pain interference, and flourishing via pain acceptance.

Conclusions

Self‐enhancing humor style could potentially help individuals with chronic pain to gain perspective and distance themselves from the situation through the acceptance of pain‐related negative emotions.

Significance

Very few studies have investigated the relationship between humor styles and adjustment in chronic pain samples. The results of the current study support the idea that adaptive dispositional traits, such as patient’s self‐ enhancing humor style, play a role in the adaptation of individuals with chronic pain. Given that the association between self‐enhancing humor style and adjustment evidenced an indirect association through pain acceptance, training in the use of humor, as individuals with self‐enhancing humor style do, might be a useful addition to ACT treatment.

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Comorbidities of self‐reported fibromyalgia in United‐States adults: A cross‐sectional study from The National Epidemiological Survey on Alcohol and Related Conditions (NESARC‐III)

Abstract

Background

Fibromyalgia has been associated with various physical and mental disorders. However, these comorbidities need to be quantified in a population‐based study.

Method

We compared participants with and without self‐reported fibromyalgia to assess (1) The prevalence of self‐reported fibromyalgia and its sociodemographic characteristics in a US representative sample, (2) The associations between self‐reported fibromyalgia and lifetime and past 12‐months mental and physical disorders, and (3) The quality of life associated with self‐reported fibromyalgia.

This cross‐sectional study used a large national sample (n=36,309) of the US population, the NESARC‐III. Face to face interviews were conducted, collecting socio‐demographic characteristics, DSM‐5 structured diagnosis, and self‐reported medical conditions (including fibromyalgia).

Results

The past 12 months prevalence of self‐reported fibromyalgia was estimated at 2.05%. Participants with self‐reported fibromyalgia were significantly at higher risk to report a lifetime history of mental disorder (adjusted odds ratio (aOR) = 2.32). Self‐reported fibromyalgia was also positively associated with 24 of the 27 physical conditions assessed in this study.

Participants with self‐reported fibromyalgia were more likely to report a past 12‐months history of suicide attempts (aOR = 5.81), substance use disorders (aOR = 1.40), mood disorders (aOR = 2.67), anxiety disorders (aOR = 2.75) and eating disorders (aOR = 2.45).

Participants with self‐reported fibromyalgia had lower levels of both mental and physical quality of life than those without fibromyalgia.

Conclusions

Participants with self‐reported fibromyalgia have a higher prevalence of comorbid mental and physical disorders, and lower mean levels of mental and physical quality of life than their counterparts without fibromyalgia.

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The N2pc Component as a Neural Index of Early Attention Allocation among Adults with Chronic Musculoskeletal Pain

Abstract

Recent evidence from event‐related potentials (ERPs) has identified N2 posterior contralateral (pc) amplitudes as a neural marker of early attention allocation. The N2pc has been used to evaluate attention biases (ABs) in samples with anxiety‐based problems but its utility has yet to be considered among persons with chronic pain, another group theorized to display ABs that perpetuate their difficulties. To address this gap, we assessed N2pc responses of adults with chronic pain (N = 70) and pain‐free controls (N = 70) during a dot‐probe task comprising painful‐neutral and happy‐neutral facial expression image pairs. Analyses indicated that (1) larger N2pc amplitudes were elicited by both painful and happy expressions compared to complementary neutral expressions in each sample, (2) the chronic pain sample displayed larger N2pc amplitudes during exposure to both painful and happy expressions than controls did, and (3) no group differences were evident for N2pc latencies. Overall N2pc results reflected general biases in early allocation of attention toward affectively‐valenced expressions rather than pain‐specific ABs among chronic pain cohorts.

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Association of quantitative sensory testing parameters with clinical outcome in patients with lumbar radiculopathy undergoing microdiscectomy

Abstract

This study aimed to establish the somatosensory profile of patients with lumbar radiculopathy at pre‐and post‐microdiscectomy and to explore any association between pre‐surgical quantitative sensory test (QST) parameters and post‐surgical clinical outcomes.

A standardized QST protocol was performed in 53 patients (mean age 38±11years, 26 females) with unilateral L5/S1 radiculopathy in the main pain area (MPA), affected dermatome and contralateral mirror sites and in age‐ and gender‐,and body site matched healthy controls. Repeat measures at three months included QST, the Oswestry Disability Index (ODI) and numerous other clinical measures; at 12 months, only clinical measures were repeated. A change <30% on the ODI was defined as ‘no clinically meaningful improvement’.

Patients showed a significant loss of function in their symptomatic leg both in the dermatome (thermal, mechanical, vibration detection p<0.002), and MPA (thermal, mechanical, vibration detection, mechanical pain threshold, mechanical pain sensitivity p<0.041), and increased cold sensitivity in the MPA (p<0.001). Pre‐surgical altered QST parameters improved significantly post‐surgery in the dermatome (p<0.018) in the symptomatic leg and in the MPA (p<0.010), except for thermal detection thresholds and cold sensitivity. Clinical outcomes improved at three and 12 months (p<0.001). Seven patients demonstrated <30% change on the ODI at 12 months. Baseline loss of function in mechanical detection in the MPA was associated with <30% change on the ODI at 12 months (OR 2.63, 95% CI 1.09‐6.37, p = 0.032).

Microdiscectomy resulted in improvements in affected somatosensory parameters and clinical outcomes. Pre‐surgical mechanical detection thresholds may be predictive of clinical outcome.

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Stuck on pain? Assessing children’s vigilance and awareness of pain sensations

Abstract

Background

Attending towards pain is proposed as a key mechanism influencing the experience and chronification of pain. Persistent attention toward pain is proposed to drive poor outcomes in both adults and children with chronic pain. However, there are no validated self‐report measures of pain‐related attention for children.

Methods

The goals of this study were to adapt the Pain Vigilance and Awareness Questionnaire (PVAQ) for use in a child sample, to preliminary examine its psychometric properties, and to assess its utility over and above a measure of general attentional capacities. We adapted the language of the PVAQ to be more easily understood by children as young as 8 years. In a sample of 160 children (8‐18 years) with chronic pain, we examined the factor structure, internal consistency, and criterion validity of the PVAQ‐C.

Results

The PVAQ‐C demonstrated excellent internal consistency (α = .92) and moderate‐to‐strong criterion validity. A one‐factor structure best fit the data. Children who reported greater attention to pain also reported greater pain catastrophizing, fear of pain, avoidance of activities, and poorer physical functioning. Pain‐related attention remained a significant predictor of functioning while controlling for demographics, catastrophizing, and fear‐avoidance. Pain‐related attention also significantly predicted child outcomes independent of the child’s general attention control capacities, indicating added value of a pain‐specific measure of attention.

Conclusions

The PVAQ‐C shows strong indices of internal reliability and criterion validity, and indicates unique predictive utility. It will be important to study the role of pain‐related attention in youth within developmental and functional‐motivational frameworks.

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FAMILY HISTORY INFLUENCES THE EFFECTIVENESS OF HOME-EXERCISE IN OLDER PEOPLE WITH CHRONIC LOW BACK PAIN: A SECONDARY ANALYSIS OF A RANDOMISED CONTROLLED TRIAL

Publication date: Available online 4 May 2020

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Joshua R. Zadro, Debra Shirley, Tom IL. Nilsen, Paul J. Mork, Paulo H. Ferreira

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