Does physiotherapy change pain and function in young adults with symptoms from femoroacetabular impingement? A pilot project for a randomised controlled trial

Psychological distress in acute low back pain: A review of measurement scales and levels of distress reported in the first two months after pain onset

Positive feedback regulation between microRNA-132 and CREB in spinal cord contributes to bone cancer pain in mice

Abstract

Background

cAMP response element-binding protein (CREB)-dependent gene expression plays an important role in central sensitization. CREB-regulated transcription coactivator 1 (CRTC1) dramatically increase CREB-mediated transcriptional activity. microRNA-132 (miR-132), which is highly CREB-responsive, functions downstream from CREB/CRTC1 to mediate activity-dependent synaptic plasticity and in turn loops back to amplify CREB/CRTC1 signalling. This study aimed to investigate the positive feedback regulation between miR-132 and CREB in spinal cord in the maintenance of bone cancer pain.

Methods

Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeNCrlVr mice to induce bone cancer pain. We further investigated effects of repeated intrathecal administration with Adenoviruses expressing CREB-siRNA or miR-132 antisense locked nucleic acid (LNA), respectively, on nociceptive behaviours and on the activity of CREB/CRTC1 signalling.

Results

Intramedullary inoculation of osteosarcoma cells resulted in up-regulation of spinal p-CREB, CRTC1 and CREB-target genes (NR2B and miR-132). Repeated intrathecal administration with Adenoviruses expressing CREB-siRNA or miR-132 LNA-AS, respectively, attenuated bone cancer-evoked pain behaviours, reduced the activity of CREB/CRTC1 signalling and down-regulated CREB-target gene NR2B expression in spinal cord.

Conclusions

These findings suggest that activation of spinal CREB/CRTC1 signalling may play an important role in bone cancer pain. Interruption to the positive feedback regulation between CREB/CRTC1 and its target gene miR-132 can effectively relieved the bone cancer-induced mechanical allodynia and spontaneous pain.

What does this study add?

The positive feedback regulation between CREB/CRTC1 and its target gene miR-132 in spinal cord plays an important role in bone cancer pain.

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Central sensitization as the mechanism underlying pain in joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type

Abstract

Background

Patients with joint hypermobility syndrome/Ehlers–Danlos syndrome, hypermobility type (JHS/EDS-HT) commonly suffer from pain. How this hereditary connective tissue disorder causes pain remains unclear although previous studies suggested it shares similar mechanisms with neuropathic pain and fibromyalgia.

Methods

In this prospective study seeking information on the mechanisms underlying pain in patients with JHS/EDS-HT, we enrolled 27 consecutive patients with this connective tissue disorder. Patients underwent a detailed clinical examination, including the neuropathic pain questionnaire DN4 and the fibromyalgia rapid screening tool. As quantitative sensory testing methods, we included thermal-pain perceptive thresholds and the wind-up ratio and recorded a standard nerve conduction study to assess non-nociceptive fibres and laser-evoked potentials, assessing nociceptive fibres.

Results

Clinical examination and diagnostic tests disclosed no somatosensory nervous system damage. Conversely, most patients suffered from widespread pain, the fibromyalgia rapid screening tool elicited positive findings, and quantitative sensory testing showed lowered cold and heat pain thresholds and an increased wind-up ratio.

Conclusions

While the lack of somatosensory nervous system damage is incompatible with neuropathic pain as the mechanism underlying pain in JHS/EDS-HT, the lowered cold and heat pain thresholds and increased wind-up ratio imply that pain in JHS/EDS-HT might arise through central sensitization. Hence, this connective tissue disorder and fibromyalgia share similar pain mechanisms.

What does this study add?

In patients with JHS/EDS-HT, the persistent nociceptive input due to joint abnormalities probably triggers central sensitization in the dorsal horn neurons and causes widespread pain.

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Does catastrophic thinking enhance oesophageal pain sensitivity? An experimental investigation

Abstract

Background

Gastro-oesophageal reflux disease (GORD) is a major health problem that is frequently accompanied by debilitating oesophageal pain symptoms.

Objectives

The first objective of the study was to examine the association between catastrophizing and oesophageal pain sensitivity. The second objective was to examine whether catastrophizing was associated with the magnitude of acid-induced oesophageal sensitization.

Methods

Twenty-five healthy volunteers (median age: 24.0 years; range: 22–31) were recruited and were asked to complete the Pain Catastrophizing Scale (PCS). During two subsequent study visits, mechanical, thermal, and electrical pain sensitivity in the oesophagus was assessed before and after inducing oesophageal sensitization using a 30-min intraluminal oesophageal acid perfusion procedure.

Results

Analyses were conducted based on data averaged across the two study visits. At baseline, catastrophizing was significantly associated with mechanical (r = −0.42, p < 0.05) and electrical (r = −0.60, p < 0.01) pain thresholds. After acid perfusion, catastrophizing was also significantly associated with mechanical (r = −0.58, p < 0.01) and electrical (r = −0.50, p < 0.05) pain thresholds. Catastrophizing was not significantly associated with thermal pain thresholds. Subsequent analyses revealed that catastrophizing was not significantly associated with the magnitude of acid-induced oesophageal sensitization.

Conclusion

Taken together, findings from the present study suggest that catastrophic thinking exerts an influence on oesophageal pain sensitivity, but not necessarily on the magnitude of acid-induced oesophageal sensitization.

What does this study add?

Catastrophizing is associated with heightened pain sensitivity in the oesophagus. This was substantiated by assessing responses to noxious stimulation of the oesophagus using an experimental paradigm mimicking features and symptoms experienced by patients with gastro-oesophageal reflux disease (GORD).

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Pain-catastrophizing and fear-avoidance beliefs as mediators between post-traumatic stress symptoms and pain following whiplash injury – A prospective cohort study

Abstract

Background

Knowledge about the course of recovery after whiplash injury is important. Most valuable is identification of prognostic factors that may be reversed by intervention. The mutual maintenance model outlines how post-traumatic stress symptoms (PTSS) and pain may be mutually maintained by attention bias, fear, negative affect and avoidance behaviours. In a similar vein, the fear-avoidance model describes how pain-catastrophizing (PCS), fear-avoidance beliefs (FA) and depression may result in persistent pain. These mechanisms still need to be investigated longitudinally in a whiplash cohort.

Methods

A longitudinal cohort design was used to assess patients for pain intensity and psychological distress after whiplash injury. Consecutive patients were all contacted within 3 weeks after their whiplash injury (n = 198). Follow-up questionnaires were sent 3 and 6 months post-injury. Latent Growth Mixture Modelling was used to identify distinct trajectories of recovery from pain.

Results

Five distinct trajectories were identified. Six months post-injury, 64.6% could be classified as recovered and 35.4% as non-recovered. The non-recovered (the medium stable, high stable and very high stable trajectories) displayed significantly higher levels of PTSS, PCS, FA and depression at all time points compared to the recovered trajectories. Importantly, PCS and FA mediated the effect of PTSS on pain intensity.

Conclusions

The present study adds important knowledge about the development of psychological distress and pain after whiplash injury. The finding, that PCS and FA mediated the effect of PTSS on pain intensity is a novel finding with important implications for prevention and management of whiplash-associated disorders.

What does this study add?

The study confirms the mechanisms as outlined in the fear-avoidance model and the mutual maintenance model.

The study adds important knowledge of pain-catastrophizing and fear-avoidance beliefs as mediating mechanisms in the effect of post-traumatic stress on pain intensity. Hence, cognitive behavioural techniques targeting avoidance behaviour and catastrophizing may be beneficial preventing the development of chronic pain.

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Social functioning in adulthood: Understanding long-term outcomes of adolescents with chronic pain/fatigue treated at inpatient rehabilitation programs

Abstract

Background

Chronic pain and fatigue are both common complaints in childhood and adolescence and often persist over time. The aim of the study was to investigate whether chronic pain/fatigue persists during adulthood and how former patients function and participate in society as adults.

Methods

This historical cohort study used questionnaires to gather the data. Predictors for social participation in adulthood were also identified. Differences in functioning and health care use between young adults with current pain/fatigue complaints and those without were also discussed.

Results

Ninety-four young adults responded; their mean age was 26.6 years and 91.5% were women. The average time since treatment was 10.2 years. 63.4% reported ongoing or new pain/fatigue complaints. 72.0% had a paid job; of those who worked, 22.1% reported taking sick leave in the past month. 78.7% of them reported having one or more chronic diseases.

A higher level of pain/fatigue measured pre-treatment was identified as a predictor for more impaired social participation in adulthood. Young adults with current pain/fatigue complaints reported more healthcare utilization, lower levels of physical functioning and limitations in daily activities due to physical problems.

Conclusions

A considerable number of these young adults still have pain/fatigue complaints in adulthood. More pain/fatigue pre-treatment during adolescence predict impaired functioning in the work-educational domain in young adulthood.

What does this study add?

This study examines the social participation of young adults who suffered from severe chronic pain/fatigue during adolescence.

Predictors for social participation are reported, as are the differences between young adults with and without persistent pain/fatigue complaints.

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Overlap and differences between patient and provider expectations for treatment outcomes: the case of acupuncture

Our study aimed to identify patient-provider clusters with different patterns of expectations for treatment outcomes. All patients (n= 885) received acupuncture treatment from physicians for their migraine, headache, osteoarthritis, or chronic low back pain. We identified six robust patient-provider expectation clusters (PPECs) (inter-classification reliability > 0.89) showing differences between patients and providers in their expected treatment responses (e.g., unrealistic optimists, optimistic doubters).

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Cross-Sectional Examination of the Associations Between Symptoms, Community Integration, and Mental Health in Multiple Sclerosis

What Is Evidence-Based About Myofascial Chains: A Systematic Review

Editorial Board

Insight into B5-I spinal interneurons and their role in the inhibition of itch and pain

No abstract available

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Postnatal maturation of the spinal-bulbo-spinal loop: brainstem control of spinal nociception is independent of sensory input in neonatal rats

Abstract: The rostroventral medial medulla (RVM) is part of a rapidly acting spino-bulbo-spinal loop that is activated by ascending nociceptive inputs and drives descending feedback modulation of spinal nociception. In the adult rat, the RVM can facilitate or inhibit dorsal horn neuron inputs but in young animals descending facilitation dominates. It is not known whether this early life facilitation is part of a feedback loop. We hypothesized that the newborn RVM functions independently of sensory input, before the maturation of feedback control. We show here that noxious hind paw pinch evokes no fos activation in the RVM or the periaqueductal gray at postnatal day (P) 4 or P8, indicating a lack of nociceptive input at these ages. Significant fos activation was evident at P12, P21, and in adults. Furthermore, direct excitation of RVM neurons with microinjection of DL-homocysteic acid did not alter the net activity of dorsal horn neurons at P10, suggesting an absence of glutamatergic drive, whereas the same injections caused significant facilitation at P21. In contrast, silencing RVM neurons at P8 with microinjection of lidocaine inhibited dorsal horn neuron activity, indicating a tonic descending spinal facilitation from the RVM at this age. The results support the hypothesis that early life descending facilitation of spinal nociception is independent of sensory input. Since it is not altered by RVM glutamatergic receptor activation, it is likely generated by spontaneous brainstem activity. Only later in postnatal life can this descending activity be modulated by ascending nociceptive inputs in a functional spinal-bulbo-spinal loop.

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Widespread pain sensitization after partial infraorbital nerve transection in MRL/MPJ mice

Abstract: Clinical studies show that chronic pain can spread to adjacent or even distant body regions in some patients. However, little is known about how this happens. In this study, we found that partial infraorbital nerve transection (p-IONX) in MRL/MPJ mice induced not only marked and long-lasting orofacial thermal hyperalgesia but also thermal hyperalgesia from day 3 postoperatively (PO) and tactile allodynia from day 7 PO in bilateral hind paws. Pain sensitization in the hind paw was negatively correlated with facial thermal hyperalgesia at early but not late stage after p-IONX. After a rapid activation of c-Fos, excitability and excitatory synaptic neurotransmission in lumbar dorsal horn neurons were elevated from day 3 and day 7 PO, respectively. In addition, microglial activation after p-IONX transmitted caudally from the Vc in the medulla to lumber dorsal horn in a time-dependent manner. Inhibition of microglial activation by minocycline at early but not late stage after p-IONX postponed and attenuated pain sensitization in the hind paw. These results indicate that neuropathic pain after p-IONX in MRL/MPJ mice spreads from the orofacial region to distant somatic regions and that a rostral–caudal transmission of central sensitization in the spinal cord is involved in the spreading process of pain hypersensitivity.

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Association between widespread pain scores and functional impairment and health-related quality of life in clinical samples of children

Pain involving several body regions generally represents nervous system pathophysiology shifting from predominantly peripheral to more central. In adults, higher widespread pain scores are clinically meaningful and confer risk for poor response to treatment. It is unknown whether widespread pain is similarly important in children. To address this gap, we conducted an observational study examining (1) associations between widespread pain and functional impairment and health-related quality of life (HRQOL) in clinical pediatric samples, and (2) associations among sociodemographic factors and pain catastrophizing with widespread pain scores.

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Musculoskeletal complaints in transverse upper limb reduction deficiency and amputation in the Netherlands: prevalence, predictors, and impact on health

Primary sensory and motor cortex function in response to acute muscle pain: A systematic review and meta-analysis

Abstract

Acute muscle pain has both motor and sensory consequences, yet the effect of muscle pain on the primary sensory (S1) and motor (M1) cortices has yet to be systematically evaluated. Here we aimed to determine the strength of the evidence for (1) altered activation of S1/M1 during and after pain, (2) the temporal profile of any change in activation and (3) the relationship between S1/M1 activity and the symptoms of pain. In September 2015, five electronic databases were systematically searched for neuroimaging and electrophysiological studies investigating the effect of acute experimental muscle pain on S1/M1 in healthy volunteers. Demographic data, methodological characteristics and primary outcomes for each study were extracted for critical appraisal. Meta-analyses were performed where appropriate. Twenty-five studies satisfied the inclusion criteria. There was consistent evidence from fMRI for increased S1 activation in the contralateral hemisphere during pain, but insufficient evidence to determine the effect at M1. Meta-analyses of TMS and EEG data revealed moderate to strong evidence of reduced S1 and corticomotor excitability during and following the resolution of muscle pain. A comprehensive understanding of the temporal profile of altered activity in S1/M1, and the relationship to symptoms of pain, is hampered by differences in methodological design, pain modality and pain severity between studies. Overall, the findings of this review indicate reduced S1 and corticomotor activity during and after resolution of acute muscle pain, mechanisms that could plausibly underpin altered sensorimotor function in pain.

What does this review add?

We provide the first systematic evaluation of the primary sensory (S1) and motor (M1) cortex response to acute experimental muscle pain in healthy volunteers. We present evidence from a range of methodologies to provide a comprehensive understanding of the effect of pain on S1/M1. Through meta-analyses we evaluate the strength of evidence concerning the direction and temporal profile of the S1/M1 response to acute muscle pain.

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The prokineticin Bv8 sensitizes cutaneous terminals of female mice to heat

Abstract

Background

Injection of the noxious peptide Bv8 has previously been shown to induce a biphasic thermal hyperalgesia in rodents, the first peak presumably due to peripheral sensitization. This hypothesis has never been directly confirmed. We have assessed whether Bv8 can indeed sensitize peripheral nerve fibres in the mouse to heat.

Methods

We used recordings from single cutaneous fibres, cutaneous calcitonin gene-related peptide (CGRP) release and immunostaining in nerves and plantar skin to evaluate the Bv8 effects on cutaneous nerves.

Results

Application of Bv8 at nanomolar concentrations (30–310 nmol/L) to skin preparations significantly increased the heat-induced discharge, the heat-induced afterdischarge and reduced threshold temperature of single unmyelinated polymodal fibres. Furthermore, application of Bv8 to hind-paw skin flaps or trigeminal ganglia significantly elevated their heat-induced CGRP release. Capsaicin-induced and to a lesser extent also KCl-induced CGRP releases were also augmented after Bv8 treatment. Immunohistochemistry revealed co-localization of prokineticin 2 (Bv8 ortholog in rodents) and CGRP in both plantar skin and nerve tissues. These results confirm that Bv8 sensitizes cutaneous nerve endings to heat, partly, although not exclusively through TRPV1 activation.

Conclusion

Our results thus support the hypothesis that the first hyperalgesic phase to follow Bv8 injection to hind paws of intact animals is due to peripheral sensitization of nociceptors.

What does this study add?

Our data provide mechanistic insights into the effect Bv8 application exerts on afferent nerve endings and into the concomitant development of thermal hyperalgesia.

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Neonatal paracetamol treatment reduces long-term nociceptive behaviour after neonatal procedural pain in rats

Abstract

Background

Pain from skin penetrating procedures (procedural pain) during infancy in the neonatal intensive care unit (NICU) may result in changes of nociceptive sensitivity in later life. This supports the need for pain management during such vulnerable periods in life. This study, therefore, analyses the short- and long-term consequences of neonatal paracetamol (acetaminophen) treatment on pain behaviour in an experimental rat model of neonatal procedural pain.

Methods

A repetitive needle-prick model was used, in which neonatal rats received four needle pricks into the left hind paw per day from postnatal day 0 to day 7 (P0–P7). Paracetamol (50 mg/kg/day s.c.) was administered daily (P0–P7), and sensitivity to mechanical stimuli was compared with a needle-prick/saline-treated group and to a tactile control group. At 8 weeks of age, all animals underwent an ipsilateral paw-incision, modelling postoperative pain, and the duration of hypersensitivity was assessed.

Results

Neonatal paracetamol administration had no effect upon short-term mechanical hypersensitivity during the first postnatal week or upon long-term baseline sensitivity from 3 to 8 weeks. However, neonatal paracetamol administration significantly reduced the postoperative mechanical hypersensitivity in young adults, caused by repetitive needle pricking.

Conclusion

Paracetamol administration during neonatal procedural pain does not alter short-term or long-term effects on mechanical sensitivity, but does reduce the duration of increased postoperative mechanical hypersensitivity in a clinically relevant neonatal procedural pain model.

What does this study add

• Paracetamol can be used safely in neonatal rats.
• Neonatal paracetamol treatment had no effect upon short-term mechanical hypersensitivity during the first postnatal week, nor upon long-term baseline sensitivity from 3 to 8 weeks.
• Paracetamol treatment during the first postnatal week significantly reduced the postoperative mechanical hypersensitivity in young adult rats.

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Effects of the noncompetitive N-methyl-d-aspartate receptor antagonists ketamine and MK-801 on pain-stimulated and pain-depressed behaviour in rats

Abstract

Background

Pain is a significant public health concern, and current pharmacological treatments have problematic side effects and limited effectiveness. N-methyl-d-aspartate (NMDA) glutamate receptor antagonists have emerged as one class of candidate treatments for pain because of the significant contribution of glutamate signalling in nociceptive processing.

Methods

This study compared effects of the NMDA receptor antagonists ketamine and MK-801 in assays of pain-stimulated and pain-depressed behaviour in rats. The nonsteroidal anti-inflammatory drug ketoprofen was examined for comparison as a positive control. Intraperitoneal injection of dilute acid served as an acute visceral noxious stimulus to stimulate a stretching response or depress intracranial self-stimulation (ICSS) in male Sprague–Dawley rats.

Results

Ketamine (1.0–10.0 mg/kg) blocked acid-stimulated stretching but failed to block acid-induced depression of ICSS, whereas MK-801 (0.01–0.1 mg/kg) blocked both acid-stimulated stretching and acid-induced depression of ICSS. These doses of ketamine and MK-801 did not alter control ICSS in the absence of the noxious stimulus; however, higher doses of ketamine (10 mg/kg) and MK-801 (0.32 mg/kg) depressed all behaviour. Ketoprofen (1.0 mg/kg) blocked both acid-induced stimulation of stretching and depression of ICSS without altering control ICSS.

Conclusion

These results support further consideration of NMDA receptor antagonists as analgesics; however, some NMDA receptor antagonists are more efficacious at attenuating pain-depressed behaviours.

What does this study add

NMDA receptor antagonists produce dissociable effects on pain-depressed behaviour.

Provides evidence that pain-depressed behaviours should be considered and evaluated when determining the antinociceptive effects of NMDA receptor antagonists.

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Resilience moderates the association between chronic pain and depressive symptoms in the elderly

Abstract

Background

Chronic pain is frequent in elderly people and, especially if widespread, associated with poor mental health. We investigated whether a resilient personality protects older adults against the adverse effects of chronic pain.

Methods

Pain status [no pain, chronic local pain (CLP) and chronic widespread pain (CWP)] was determined using the American College of Rheumatologists' criteria for widespread pain in a cross-sectional sample of 724 participants aged 68–92 years drawn from the population-based KORA-Age study in Southern Germany. Depressive symptoms and resilience were assessed via the scales GDS-15 and RS-5. The relation between pain, resilience and depressive symptoms was modelled using logistic and quantile regression.

Results

CLP prevalence and CWP prevalence were 57.5% and 12.3%, respectively. Confounder-adjusted logistic regression indicated a fourfold risk of depressed mood (GDS-15 ≥ 5) in CWP, vs. no pain (OR = 4.08, 95% CI 1.90–8.74). However, in quantile regression, the adverse effect of CWP was significantly attenuated by resilience when looking at the GDS-15 score lower quartile (p = 0.011) and median (p = 0.011). This effect appeared to be mainly driven by participants aged 75–84 years. Confounder adjustment reduced the effect of CLP on depressive symptoms to non-significance, and effect modification by resilience was undetectable in regression models of CLP.

Conclusions

Resilience was protective in the association of CWP with depressive symptoms in this analysis. Older adults with CWP may potentially benefit from interventions supporting resilience. Prospective research should investigate the protective role of resilience in the potentially self-perpetuating relation between chronic pain and depressed affect.

What does this study add?

The association of chronic widespread pain with depressive symptoms in the elderly population is attenuated by resilience.

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Analgesia by telemedically supported paramedics compared with physician-administered analgesia: A prospective, interventional, multicentre trial

Abstract

Background

In German emergency medical services (EMS), the analgesia is restricted to physicians. In this prospective, interventional, multicentre trial, complications with and quality of telemedically delegated analgesia were evaluated.

Methods

If prehospital analgesia was necessary, five telemedically equipped paramedic ambulances from four different districts could consult a telemedicine centre. Analgesics were delegated based on a predefined algorithm. Telemedically assisted cases were compared with local historical regular EMS missions using matched pairs. The primary outcome was the frequency of therapeutic complications (respiratory/circulatory insufficiency, allergic reactions). Secondary outcomes were quality of analgesia (11-point numerical rating scale, NRS) and the frequency of nausea/vomiting.

Results

Analgesia was necessary in 106 telemedically assisted missions. In 23 cases, the telemedical procedure was used until an EMS physician arrived. Of the remaining 83 cases, 80 could be matched to comparable controls. Complications did not occur in either the study group or the control group (0 vs. 0; p = N/A). Complete NRS documentation was noted in 65/80 (study group) and 32/80 (control group) cases (p < 0.0001). Adequate initial pain reduction (quality indicator: reduction of NRS ≥ 2 points or NRS < 5 at end of mission) occurred in 61/65 versus 31/32 cases (p = 1.0); NRS reduction during mission was 3.78 ± 2.0 versus 4.38 ± 2.2 points (p = 0.0159). Nausea and vomiting occurred with equal frequency in both groups.

Conclusions

Telemedical delegation of analgesics to paramedics was safe and led to a pain reduction superior to the published minimum standard in both groups. The documentation quality was better in the telemedicine group.

What does this study add?

Little is known about the safety and quality of prehospital analgesia carried out by emergency medical services (EMS). Beside potential quality problems, in some countries meaningful pain reduction is limited by legal regulations that allow only physicians to administer analgesics.

This first multicentre prospective trial for telemedically delegated analgesia demonstrates that remote analgesia is possible and safe and retains equivalent analgesic quality compared with that administered by onsite EMS physicians.

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Experimental pain sensitivity in multiple system atrophy and Parkinson's disease at an early stage

Abstract

Background

Chronic spontaneous pain is a clinically relevant non-motor symptom in multiple system atrophy (MSA) and Parkinson's disease (PD). Experimental pain sensitivity, reflecting the mechanisms of nociception and pain perception leading to clinical pain, is known to be enhanced in both diseases at advanced stages. Also, this study aimed at investigating experimental pain sensitivity already at an early stage (i.e. symptom duration ≤5 years).

Methods

Experimental pain sensitivity was assessed by investigating the nociceptive flexion reflex (NFR, reflecting spinal nociception) and heat and electrical pain thresholds. ‘Off-drug’ MSA (n = 11) and PD (n = 14) patients selected at an early stage of the disease were compared to healthy controls (HC, n = 27). MSA patients had either parkinsonian (MSA-P, n = 5) or cerebellar (MSA-C, n = 6) subtypes.

Results

Compared to HC, MSA patients had lower heat pain sensitivity, whereas PD patients had reduced NFR threshold. MSA and PD patients did not differ from HC regarding other variables. MSA-P and MSA-C patients did not differ, either.

Conclusions

Impaired sensory discrimination and attention deficits could contribute to the reduced perception of heat pain in MSA, whereas in PD, local changes in spinal excitability or a diminished dopaminergic descending inhibition might impact on the motor efference of the NFR to reduce its threshold to nociceptive afferent information.

What does this study add?

This study investigated experimental pain sensitivity at an early stage in MSA and PD.

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Algoplus performance to detect pain in depressed and/or demented old patients

Abstract

Background

Algoplus detects acute pain in non-verbal old patients (NVOP) with good psychometric properties. However, depression or dementia might modify the Algoplus score and/or item expression. Algoplus performances on demented and/or depressed old populations were tested.

Methods

This multicentre cross-sectional study included patients ≥65 years old with or without pain assigned to depression, dementia, depression & dementia or control groups. Each group was subjected to the Numerical Rating Scale (NRS) and behavioural scales (Algoplus, Doloplus). Depression and/or dementia status was rated and confirmed by blinded experts. Algoplus psychometric properties tested were: discriminant validity, convergent validity, item analysis, sensitivity to change after pain treatment and threshold determination.

Results

The analysis included 171 patients (mean age 82.3 ± 6.3 years). Patients with and without pain in each group were comparable for age in all subgroups, except the older dementia subgroup. The mean Algoplus score was significantly higher for patients with than without pain, regardless of group assignment (Wilcoxon signed-rank test, p < 0.001). Algoplus and NRS or Doloplus had high convergent validity (respective Spearman correlation coefficients 0.79 and 0.87). The mean Algoplus score decreased significantly after starting pain management, regardless of group assignment. Some behaviours (i.e. “look”) occurred more often in depressed patients, even those without pain. A threshold of 2 yielded respective sensitivity and specificity values of 95% and 96% for dementia patients, 62% and 79% for depressed patients, 96% and 71% for dementia & depressed patients, and 80% and 100% for controls.

Conclusion

Algoplus accurately detected pain in depressed and/or dementia patients; and was sensitive to change after pain treatment.

What does this study add?

Algoplus accurately detects pain in depressed and/or demented patients.

A cut-off score of 2 accurately detects the need for pain management in these populations.

Algoplus is sensitive to change after treating pain.

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Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain

This Clinical Evidence Synopsis summarizes a Cochrane review on the efficacy of topical nonsteroidal anti-inflammatory drugs to treat musculoskeletal conditions, such as sprains, strains, and contusions.

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Antiplatelet Drug Does Not Reduce Sickle Cell Pain

Children and adolescents with sickle cell anemia who received the adenosine diphosphate–directed antiplatelet agent prasugrel had no significant reduction in painful vasoocclusive crises compared with those who received placebo, found a trial conducted in 13 countries (Heeney MM et al. N Engl J Med. doi:10.1056/NEJMoa1512021 [published online December 8, 2015]). Previous studies had suggested that prasugrel reduced markers of platelet activation and, consequently, the rate and intensity of vasoocclusive pain in sickle cell anemia.

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The Evaluation of Donor Site Pain After Harvest of Tricortical Anterior Iliac Crest Bone Graft for Spinal Surgery: A Prospective Study

Study Design. A prospective cohort. Objective. The aim of this study was to prospectively observe donor site pain, health-related quality-of-life outcomes, and complications following harvest of tricortical anterior iliac crest bone graft (AICBG) for anterior cervical discectomy and fusion (ACDF). Summary of Background Data. Persistent donor site pain from the anterior iliac crest has been reported to range between 2% and 40%. This morbidity has led surgeons to consider interbody alternatives for ACDF, which carry additional costs. Methods. We prospectively enrolled 50 patients from 2 tertiary care centers over the course of 1 year observing complications and patient-reported outcomes. Patients filled out SF-12 and numeric rating scale (NRS) for pain in the arm, neck, and donor site pre-operatively and at 1 week, 2 weeks, 6 weeks, 3 to 6 months, and 1 year postoperatively. Outcomes were compared with a control group undergoing ACDF with allograft or Polyether ether ketone cages at 1 year. Results. The mean ± SD donor site pain at 1 week was 5.6 ± 2.8 but decreased to 2.2 ± 2.4 at 6 weeks and 1.1 ± 1.8 at 1 year (P < 0.001). Including the 3 patients who were lost to follow-up, 10% of patients may have experienced persistent moderate or worse pain at 1 year. Linear regression analysis demonstrated that preoperative opioid use was an independent risk factor for increased donor site pain at 1 and 2 weeks (P < 0.05). There were no differences in outcomes at 1 year compared with the nonautograft group. There were 2 (4%) minor wound complications, both treated successfully with oral antibiotics. Conclusion. Tricortical AICBG for ACDF is not associated with major complications and only 4% of patients (potentially, maximum of 10%) experienced moderate, persistent donor site pain at 1 year. There is no difference in health-related outcomes between patients who have autograft with those who did not at 1 year. Preoperative opioid use is associated with increased donor site pain within the first 2 weeks postoperatively but not in the long term. At 6 weeks postoperatively, patients can expect the majority of their donor site pain to be resolved. Level of Evidence: 2

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Neurologic Complications, Reoperation, and Clinical Outcomes After Surgery for Vertebral Osteomyelitis

Study Design. A consecutive retrospective cohort study from 2008 to 2013 at a single tertiary-care institution was conducted. Objective. The aim of the study was to characterize recovery from pain and neurologic deficit after surgery for vertebral osteomyelitis (VO), and identify incidence of postoperative adverse events. Summary of Background Data. A minority of patients with VO require surgery. Although prior studies have characterized outcomes after medical management, the morbidity after surgery is poorly defined. Methods. The primary outcome was change from baseline in a Modified McCormick Scale (MMS, 1–5 scale), whereas secondary outcomes included reoperation and change in self-reported pain Visual Analog Scale (VAS, 0–10 scale). MMS and VAS were collected throughout the postoperative course as surrogates for neurologic function and degree of pain. Intraoperative, short-term postoperative (<30 d), and long-term neurologic complications were recorded. New-onset neurologic deficits in the postoperative period were considered neurologic complications. Results. Fifty patients were included; a majority (52%) presented with a neurologic deficit. The median length of follow-up was 18 months. A statistically significant improvement in MMS was observed by 12 months postoperatively, whereas an improvement in VAS was observed by 3 months. The mean improvement in MMS at last follow-up was 0.35, whereas the mean improvement in VAS was 3.40. One quarter of patients required reoperation. At 24 months postoperatively, 10% died, 26% underwent reoperation, 42% experienced a neurologic complication, and 60% experienced at least one of these 3 adverse events. Conclusion. This is the first study to investigate neurologic complications, reoperation, and pain in a longitudinal manner after surgery for VO. We observed statistically significant improvements in MMS and VAS in the postoperative period. Despite these improvements, the 24-month incidence of overall adverse events was 60%. Patients and clinicians should be aware of the clinical improvement but high incidence of adverse events after surgical management of VO. Level of Evidence: 4

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Patients’ and Physiotherapists’ Views on Triggers for Low Back Pain

Study Design. A cross-sectional survey. Objective. The aim of this study was to compare patients’ and physiotherapists’ views on triggers for low back pain (LBP) and to identify any novel factors not previously reported. Summary of Background Data. Most research on risk factors for LBP is guided by the views of clinicians and researchers, not patients. Consequently, potentially valuable information about risk factors for LBP is not available from those suffering the condition. This study aimed to compare patients’ and physiotherapists’ views on triggers for LBP and to identify any novel factors not previously reported. Methods. One hundred two physiotherapists and 999 patients with a sudden, acute episode of LBP participated in this study. Participating physiotherapists were asked to nominate the most likely short-term risk factors to trigger a LBP episode. Similarly, patients were asked what they thought had triggered their onset of LBP. Responses were coded into risk factor categories and subcategories by 2 independent researchers. Endorsement of each category was compared using the Pearson Chi-square statistic. Results. Both patients and physiotherapists endorsed biomechanical risk factors as the most important risk factor category (87.7% and 89.4%, respectively) and had similar levels of endorsement for 3 of the top 5 subcategories (lifting, bending, and prolonged sitting). There were significant differences in endorsement of awkward postures (13.4% vs 1.2%; P < 0.001) sports injuries (15.9% vs 4.7%; P < 0.001), physical trauma (3.4% vs 9.2%; P < 0.001), and unaccustomed activity (2.3% vs 7.3%; P < 0.001) by patients and physiotherapists, respectively. Conclusion. Overall, patients’ and physiotherapists’ views were remarkably similar. Both patients and physiotherapists endorsed lifting as the most important trigger for LBP and agreed on 3 of the top 5 (lifting, bending, and prolonged sitting). No new risk factors were suggested by patients. Level of Evidence: 2

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Cost-Effectiveness of Surgical Versus Conservative Treatment for Thoracolumbar Burst Fractures

Study Design. Historical, register-based cohort study following 85 patients in the course of a time frame extending from 2 years before to 2 years after trauma occurrence. Objective. To investigate the cost-effectiveness of surgery versus conservative management for thoracolumbar burst fractures. Summary of Background Data. Despite the prevalence of thoracolumbar burst fractures, consensus has still not been reached in terms of their clinical management and whereas from a health policy point of view, efficient use of resources is equally important, literature pertaining to this aspect is limited. Methods. Consecutive patients who were admitted to a university clinic between 2004 and 2008 because of CT-verified AO type A3 fractures (T11-L2), age 18 to 65 years Patients with neurological compromise, osteoporosis, or malignancy were not included. The cost parameter defined primary and secondary health-care use (2010 €) and the effect parameter was based on three alternative measures of pain medication: morphine milligram and defined daily doses (DDD) of narcotic and nonnarcotic analgesics. For cost-effectiveness analysis, we employed a difference-in-difference approach, including control for treatment selection (age, sex, and fracture type). Nonparametric bootstrapping was used to estimate conventional 95% confidence intervals of mean estimates. Results. When taking into consideration all health-care consumption, surgical management was observed to cost an additional €10,734 (4215; 15,144) as compared with conservative management. The differences on morphine at 527(–3031; 6,016) milligram, narcotic analgesics at –8(–176; 127) DDD, and nonnarcotic analgesics at –3(–72; 58) DDD were all insignificant The probability for surgery being cost-effective did not exceed 50% for any value of willingness to pay for effect. Conclusion. Surgical management does not seem to be a cost-effective strategy as compared with conservative management for traumatic thoracolumbar burst fractures without neurological deficits. In addition, higher-volume studies examining the clinical effect of alternative management strategies would be valuable. Level of Evidence: 3

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A Survey of Innovative Reimbursement Models in Spine Care

Study Design. Structured key informant interviews with follow-up. Objective. The aim of the study was to describe innovative reimbursement models in spine care and gather perspectives on the future of spine care reimbursement. Summary of Background Data. The United States spends $90 billion annually on medical expenses for low back pain. One approach to promoting high-quality, cost-effective care is through bundled payments and other reimbursement models wherein physicians are held accountable for costs and utilization. Little data exist on innovative payment models in spine care. Methods. Through literature review and discussions with leaders in the field, we identified organizations that were engaged in bundled payment initiatives for spine care and surgery. These included healthcare systems, physician groups, organizations helping to set up bundles, and a large employer. We conducted interviews to understand the background and specific features of each initiative, generalizable success factors and challenges, and perspectives on the future of spine reimbursement. Results. We interviewed 24 stakeholders across 18 organizations that collectively perform approximately 12,000 inpatient spine surgeries annually. Fee-for-service reimbursement accounts for a majority of revenue, but several organizations expect 30% to 45% of their spine volume to be covered under bundled payments within 3 years and cite new patient volume, increased surgical yield, and financial benefits from efficiency improvements as reasons for adopting bundled payments. Current initiatives are heterogeneous, but share similar success factors and challenges. Institutions are more hesitant to adopt risk-based payment models for chronic back care, citing difficulty modeling risk, patient heterogeneity, and difficulty aligning incentives. Conclusion. Payment models outside of the traditional fee-for-service paradigm are emerging in spine care. Providers that preemptively adopt bundled payments can increase patient volumes from payers seeking cost-effective care. Going forward, organizations should begin considering reimbursement models that focus on noninterventional spine care. Finally, developments in spine reimbursement may apply to other procedure-based specialties, including orthopedics and cardiology. Level of Evidence: 5

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Subjective Sleep Quality Deteriorates Prior to Development of Painful Temporomandibular Disorder

There is good evidence that poor sleep quality increases risk of painful temporomandibular disorder (TMD). However little is known about the course of sleep quality in the months preceding TMD onset, and whether the relationship is mediated by heightened sensitivity to pain. The Pittsburgh Sleep Quality Index was administered at enrollment into the OPPERA prospective cohort study. Thereafter the Sleep Quality Numeric Rating Scale was administered every three months to 2,453 participants. Sensitivity to experimental pressure pain and pinprick pain stimuli was measured at baseline and repeated during follow-up of incident TMD cases (n=220) and matched TMD-free controls (n=193).

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Human Genetic Variability Contributes to Post-operative Morphine Consumption

High inter-individual variability in postoperative opioid consumption is related to genetic and environmental factors. We tested the association between morphine consumption, postoperative pain and single nucleotide polymorphisms (SNPs) within OPRM1, COMT, UGT2B7, and ESR1 gene loci to elucidate genetic prediction of opioid consumption.We analyzed 20 SNPs in 201 unrelated Caucasian patients undergone abdominal surgery receiving postoperative patient-controlled analgesia-administered morphine. Morphine consumption and pain intensity were dependent variables; age and sex covariates.

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Swimming Improves Pain and Functional Capacity of Patients with Fibromyalgia: A Randomized Controlled Trial

Ageing and Obesity indices influences the Tactile Spatial Acuity of the Low Back Regions: A cross-sectional study

Two-point discrimination threshold (TPDT) is increased in individuals with chronic low back pain. TPDT reference values and their determinants are required for clinical applications. Therefore, the aims of this research are to establish reference values for TPDT of the low back regions in healthy individuals, stratified for age, and to investigate the associations of demographic and anthropomorphic variables with TPDT.

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[Correspondence] Pre-hospital emergency medicine: pain control

The review by Mark Wilson and colleagues (Dec 19, p 2526)1 provides an excellent overview of pre-hospital emergency medicine. The authors highlight specific considerations both for clinical management and for scene management. We would like to emphasise one key element to complete the review: pain control. Pain control is a good example of how pre-hospital care has evolved in the past years.

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Hyperpigmented Reticulated Patch in an Older Man

A 67-year-old man receiving rituximab for membranous nephropathy presented with volume overload and a hyperpigmented, gray-brown patch on his mid and lower back. He reported long-term use of a heating pad for chronic back pain but denied experiencing burns or thermal trauma. What would you do next?

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Error in Flow Diagram Randomization Boxes

In the Original Investigation entitled “Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial” published in the December 22/29, 2015, issue of JAMA, 2 of the intervention groups in Figure 1 were mislabeled. In the boxes below the randomization ovals, the second box should read “103 Randomized to receive 24F chest tube and opiates” and the last box should read “28 Randomized to receive 24F chest tube and opiates.” This article was corrected online.

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Randomised controlled trial to evaluate a physiotherapy-led functional exercise programme after total hip replacement

An evaluation of central sensitization in patients with sickle cell disease

Central sensitization (CS), nociceptive hyper-excitability known to amplify and maintain clinical pain, has been identified as a leading culprit responsible for maintaining pain in several chronic pain conditions. Recent evidence suggests that it may explain differences in the symptom experience of individuals with sickle cell disease (SCD). Quantitative sensory testing (QST) can be used to examine CS and identify individuals that may have a heightened CS profile. The present study categorized patients with SCD based on QST responses into a high or low CS phenotype and compared these groups on measures of clinical pain, vaso-occlusive crises, psychosocial factors, and sleep continuity.

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Erratum to Does Chronic Pain Alter the Normal Interaction Between Cardiovascular and Pain Regulatory Systems? Pain Modulation in the Hypertensive-Monoarthritic Rat

Incorrect grant funding information was published in this article. The corrected information appears below.

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Senator questions pain panel’s ties to industry

A US senator has begun an inquiry into possible conflicts of interests among members of an expert committee that advises the US government on policy on pain treatment.The Interagency Pain Research...

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The immediate effect of sacroiliac joint manipulation on EMG of vasti and gluteus medius in athletes with patellofemoral pain syndrome: a randomized controlled trial

To evaluate the immediate effect of sacroiliac joint manipulation on EMG activity of vastus medialis, vastus lateralis and gluteus medius as well as pain and functional performance of athletes with patellofemoral pain syndrome.

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Increased Risk of Depression Recurrence After Initiation of Prescription Opioids in Noncancer Pain Patients

Several studies have shown that chronic opioid analgesic use is associated with increased risk of new-onset depression. It is not known if patients with remitted depression are at increased risk of relapse after exposure to opioid analgesics. A retrospective cohort design using patient data from the Veterans Health Administration (VHA; n = 5,400), and Baylor Scott & White Health (BSWH; n = 842) was performed with an observation period in the VHA from 2002 to 2012 and in the BSWH from 2003 to 2012.

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Evaluation of the effectiveness of three physiotherapeutic treatments for subacromial impingement syndrome: a randomised clinical trial

Current management of pregnancy-related low back pain: a national cross-sectional survey of UK physiotherapists

Effects of whole-body vibration training with quadriceps strengthening exercise on functioning and gait parameters in patients with medial compartment knee osteoarthritis: a randomised controlled preliminary study

Movement-based subgrouping in low back pain: synergy and divergence in approaches

Physiotherapy for plantar fasciitis: A UK-wide survey of current practice

Altered function of intracortical networks in chronic lateral epicondylalgia

Abstract

Background

Lateral epicondylalgia (LE) is a musculotendinous condition characterized by persistent pain, sensorimotor dysfunction and motor cortex reorganization. Although there is evidence linking cortical reorganization with clinical symptoms in LE, the mechanisms underpinning these changes are unknown. Here we investigated activity in motor cortical (M1) intracortical inhibitory and facilitatory networks in individuals with chronic LE and healthy controls.

Methods

Surface electromyography was recorded bilaterally from the extensor carpi radialis brevis (ECRB) muscle of 14 LE (4 men, 41.5 ± 9.9 years) and 14 control participants (4 men, 42.1 ± 11.1 years). Transcranial magnetic stimulation of M1 was used to evaluate resting and active motor threshold, corticomotor output, short- (SICI) and long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) of both hemispheres.

Results

In individuals with LE, SICI (p = 0.005), ICF (p = 0.026) and LICI (p = 0.046) were less in the M1 contralateral to the affected ECRB muscle compared with healthy controls. Motor cortical threshold (rest: p = 0.57, active: p = 0.97) and corticomotor output (p = 0.15) were similar between groups. No differences were observed between individuals with LE and healthy controls for the M1 contralateral to the unaffected ECRB muscle.

Conclusions

These data provide evidence of less intracortical inhibition mediated by both GABA_A and GABA_B receptors, and less intracortical facilitation in the M1 contralateral to the affected ECRB in individuals with LE compared with healthy controls. Similar changes were not present in the M1 contralateral to the unaffected ECRB. These changes may provide the substrate for M1 reorganization in chronic LE and could provide a target for future therapy.

What does this study add

Lateral epicondylalgia (LE) is a common musculoskeletal condition characterized by elbow pain and sensorimotor dysfunction. The excitability and organization of the motor cortical representation of the wrist extensor muscles is altered in LE, but the mechanisms that underpin these changes are unknown. evidence of less intracortical inhibition mediated by both GABA_A and GABA_B receptors, and less intracortical facilitation mediated by NMDA receptors, in the M1 contralateral to the affected extensor carpi radialis brevis muscle in chronic LE compared with healthy controls. Altered activity in intracortical networks may contribute to altered motor cortex organization in LE and could provide a potential target for future treatments.

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Differential contribution of orexin receptors within the ventral tegmental area to modulation of persistent inflammatory pain

Abstract

Background

Orexinergic neurons in the lateral hypothalamus (LH) play an important role in pain modulation. In addition, ventral tegmental area (VTA) is known as a part of descending pain modulatory circuitry. Little is known about the interaction between the LH and neural substrates involving in modulation of formalin-induced nociception. Accordingly, we aimed to examine the pain modulatory role of VTA orexin receptors in the formalin test.

Methods

Seventy-eight male Wistar rats were unilaterally implanted with two cannulae above the LH and VTA. Intra-VTA administration of SB-334867 (orexin-1 receptor antagonist) or TCS OX2 29 (orexin-2 receptor antagonist) was performed 5 min before intra-LH microinjection of carbachol (a cholinergic receptor agonist). The procedure was followed by subcutaneous injection of formalin after 5-min interval time.

Results

Carbachol attenuated formalin-induced biphasic pain responses and SB-334867 or TCS OX2 29 administration dose-dependently antagonized the LH-induced analgesia during both phases. Blockade of orexin-1 and -2 receptors had more profound effects on the reduction of antinociception during the late phase compared to the early phase. Also, contribution of orexin-1 receptors in mediation of LH-induced analgesia was greater than orexin-2 receptors during the late phase.

Conclusion

Formalin test, a model of persistent inflammatory pain, mimics the conditions encountered in clinical situations. Pain modulatory role of orexinergic system in the formalin test through a neural pathway from the LH to the VTA provides the evidence that orexins can be useful therapeutic targets for chronic pain treatment.

What does this study add?

There is a pathway from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) which modulates biphasic formalin-induced pain.

Blockade of VTA orexin receptors dose-dependently reduces LH-induced analgesia during both phases.

Anti-analgesic effect of orexin receptor antagonists is more considerable during the late phase.

Contribution of orexin-1 receptors to mediation of LH-induced analgesia is more than orexin-2 receptors during the late phase.

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The use of safety-seeking behavior in exposure-based treatments for fear and anxiety: Benefit or burden? A meta-analytic review

Elevation of Microglial Basic Fibroblast Growth Factor Contributes to Development of Neuropathic Pain after Spinal Nerve Ligation in Rats

Study Design. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistological analysis of spinal cord and pain behavior analysis in a rat neuropathic pain model were conducted to examine the function of microglial basic fibroblast growth factor (bFGF) in the development of neuropathic pain. Objective. To investigate the role of bFGF in spinal microglia during the development of allodynia following spinal nerve ligation in rats. Summary of Background Data. Evidence suggests that the production of bFGF by spinal cord glial cells is increased in response to peripheral nerve injury. Although an association between bFGF and astrocytes has been widely reported, the relationship between bFGF and microglia, particularly with respect to the development of neuropathic pain, remains poorly understood. Methods. Spinal nerve ligation rats were used. After surgery, bFGF expression in the spinal cord was investigated using RT-PCR and immunohistochemistry. Neutralizing antibodies to bFGF were injected intrathecally into rats after spinal nerve ligaton. Spinal cords were used for RT-PCR analysis and pain behavior was analyzed using the von Frey test. Results. bFGF mRNA expression was significantly increased in the spinal cord 6 hours after spinal nerve ligation compared with untreated rats. Immunohistochemical analysis revealed that bFGF co-localized with ionized calcium-binding adaptor molecule 1, a microglial marker, and myeloperoxidase. Neutralizing antibodies to bFGF attenuated mechanical allodynia and myeloperoxidase mRNA expression. Conclusion. bFGF increased in spinal microglia during the development allodynia after spinal nerve ligation. Thus, controlling bFGF release from microglia during the acute stage of peripheral nerve injury may suppress the progression of allodynia. Level of Evidence: N/A

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Downregulation of miR-27b is Involved in Loss of Type II Collagen by Directly Targeting Matrix Metalloproteinase 13 (MMP13) in Human Intervertebral Disc Degeneration

Study Design. A microRNA (miRNA) study. Objective. The purpose of this study was to identify intervertebral disc degeneration (IDD)-specific miRNAs, followed by functional validation of results. Summary of Background Data. IDD is the major contributor to back radicular pain, and the molecular mechanisms underlying this disease are not completely understood. Accumulating evidence suggests that miRNAs play an important role in IDD, but the role of specific miRNAs involved in this disease remains elusive. Methods. An initial screening of nucleus pulposus (NP) tissues, miRNA expression by miRNA microarray, was performed using samples from 10 patients with degenerative disc disease and 10 patients with lumbar fracture (as controls). Subsequently, differential expression was validated using quantitative reverse transcriptase PCR (qRT-PCR). The level of differentially expressed miRNAs in degenerative NP tissues was investigated, and then functional analysis of the miRNAs in regulating collagen II expression was carried out. Western blotting and luciferase reporter assays were also used to detect the target gene. Results. We identified 23 miRNAs that were differentially expressed (16 upregulated and 7 downregulated) in patients compared with controls. After qRT-PCR confirmation, miR-27b was significantly downregulated in degenerative NP tissues when compared with controls. Moreover, its level was correlated with grade of disc degeneration. Overexpression of miR-27b promoted type II collagen expression in NP cells. Bioinformatics target prediction identified matrix metalloproteinase 13 (MMP13) as a putative target of miR-27b. Futhermore, luciferase reporter assays demonstrated that miR-27b directly targets MMP13 and affects the protein expression of MMP13 in NP cells. Expression of MMP13 negatively correlated with miR-27b expression in degenerative NP tissues. Conclusion. The downregulation of miR-27b induces type II collagen loss by directly targeting MMP13, leading to the development of IDD. Our study also underscores the potential of miR-27b as a novel therapeutic target in human IDD. Level of Evidence: 3

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Association Between the Plasma Levels of Mediators of Inflammation With Pain and Disability in the Elderly With Acute Low Back Pain: Data From the Back Complaints in the Elders (BACE)-Brazil Study

Study Design. Cross-sectional study with subsample of elderly women with acute low back pain (LBP), from Back Complaints in the Elders-Brazil (BACE-Brazil) Objective. To investigate the association between plasma levels of mediators of inflammation (interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and soluble TNF receptor 1 (sTNF-R1)) with pain and disability experienced by elderly women with acute LBP. Summary of Background Data. Among the elderly, LBP is a complaint of great importance and can lead to disability. Inflammatory cytokines are elevated in painful conditions, and may promote pain. Methods. We included 155 community-dwelling elderly women (age ≥ 65 yr), who presented with a new (acute) episode of LBP. Enzyme-linked immunosorbent assays were used to measure TNF-α, sTNF-R1, IL-1β, and IL-6. Disability was assessed using the Roland Morris Disability Questionnaire; pain was assessed using the McGill Pain Questionnaire. Linear regression models were fit with each pain and disability outcome as dependent variables: Present Pain Intensity; Qualities of pain; Severity of pain in the last week; LBP frequency and disability. Results. Depressive symptoms and IL-6 were associated and explained 20.9% of “qualities of pain” variability. TNF-α, sTNFR1, education, body mass index, and depressive symptoms explained 8.4% of “Severity of pain in the past week” variability. TNF-α, education, BMI, depressive symptoms, present pain intensity, qualities of pain, and LBP frequency explained 48.6% of “disability.” No associations between inflammatory cytokines and “present pain intensity” and “LBP frequency” were found. Conclusion. Our results demonstrate associations between inflammatory markers (TNF-α and sTNFR1) and pain severity, IL-6 was associated with the qualities of pain, and TNF-α was also associated with disability. These inflammatory mediators represent new markers to be considered in the assessment and treatment of elderly patients with LBP. Level of Evidence: 5

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The Clinical Correlation of the Hart-ISSG Proximal Junctional Kyphosis Severity Scale With Health-Related Quality-of-life Outcomes and Need for Revision Surgery

Study Design. Retrospective analysis of prospective data. Objective. Evaluate the utility of the Hart-International Spine Study Group proximal junctional kyphosis severity scale (Hart-ISSG PJKSS). Summary of Background Data. Proximal junctional kyphosis (PJK) and failure (PJF) are well-described complications after long-segment instrumentation. The Hart-ISSG PJKSS was recently developed and incorporates neurological deficit, pain, instrumentation issues, degree of kyphosis, presence of fracture, and level of upper-most instrumented vertebrae. Methods. All adult spinal deformity patients with PJK or PJF were identified from two academic centers over a 7-year period. Health-related quality-of-life (HRQOL) outcomes were prospectively collected: Oswestry Disability Index (ODI), visual analogue scale (VAS) pain, SF-36 questionnaire, and SRS-30 questionnaire. Patients were retrospectively assigned Hart-ISSG PJKSS scores. Correlation between the Hart-ISSG PJKSS and outcomes was assessed with linear regression, Pearson correlation coefficients, and χ2 analysis. Results. A total of 184 cases were included; 21.2% were men and mean age was 65.0 years. Weakness and/or myelopathy were present in 11.4% of patients and 88.6% had pain. Instrumentation issues occurred in 44.0% and 64.1% had PJK-associated fractures. PJK occurred in the upper thoracic spine in 21.7% of cases. Mean PJKSS score was 5.9. The Hart-ISSG PJKSS was significantly and strongly associated with ODI (P < 0.001, r = 0.611), VAS pain (P < 0.001, r = 0.676), SRS-30 function (P < 0.001, r = −0.401), SRS-30 mental health (P < 0.001, r = −0.592), SRS-30 self-image (P < 0.001, r = −0.511), SRS-30 satisfaction (P < 0.001, r = −0.531), and SRS-30 pain (P < 0.001, r = −0.445). Higher scores were associated with higher proportion of patients undergoing revision surgery (P < 0.001); scores of 9 to 11 and 12 to 15 underwent revision 96.0% and 100.0% of the time, respectively. Conclusion. The Hart-ISSG PJKSS was strongly correlated with validated functional outcomes and higher scores were associated with higher rates of revision surgery. The Hart-ISSG PJKSS may be a useful clinical tool in the treatment of patient with PJK. Level of Evidence: 3

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The Health Impact of Symptomatic Adult Spinal Deformity: Comparison of Deformity Types to United States Population Norms and Chronic Diseases

Study Design. A retrospective analysis of a prospective, multicenter database. Objective. The aim of this study was to evaluate the health impact of symptomatic adult spinal deformity (SASD) by comparing Standard Form Version 2 (SF-36) scores for SASD with United States normative and chronic disease values. Summary of Background Data. Recent data have identified radiographic parameters correlating with poor health-related quality of life for SASD. Disability comparisons between SASD patients and patients with chronic diseases may provide further insight to the disease burden caused by SASD. Methods. Consecutive SASD patients, with no history of spine surgery, were enrolled into a multicenter database and evaluated for type and severity of spinal deformity. Baseline SF-36 physical component summary (PCS) and mental component summary (MCS) values for SASD patients were compared with reported U.S. normative and chronic disease SF-36 scores. SF-36 scores were reported as normative-based scores (NBS) and evaluated for minimally clinical important difference (MCID). Results. Between 2008 and 2011, 497 SASD patients were prospectively enrolled and evaluated. Mean PCS for all SASD was lower than U.S. total population (ASD = 40.9; US = 50; P < 0.05). Generational decline in PCS for SASD patients with no other reported comorbidities was more rapid than U.S. norms (P < 0.05). PCS worsened with lumbar scoliosis and increasing sagittal vertical axis (SVA). PCS scores for patients with isolated thoracic scoliosis were similar to values reported by individuals with chronic back pain (45.5 vs 45.7, respectively; P > 0.05), whereas patients with lumbar scoliosis combined with severe sagittal malalignment (SVA >10 cm) demonstrated worse PCS scores than values reported by patients with limited use of arms and legs (24.7 vs 29.1, respectively; P < 0.05). Conclusions. SASD is a heterogeneous condition that, depending upon the type and severity of the deformity, can have a debilitating impact on health often exceeding the disability of more recognized chronic diseases. Health care providers must be aware of the types of SASD that correlate with disability to facilitate appropriate diagnosis, treatment, and research efforts. Level of Evidence: 3.

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Repeated 3.0 Tesla Magnetic Resonance Imaging After Clinically Successful Lumbar Disc Surgery

Study Design. Prospective cohort study. Objective. To describe the naturally occurring magnetic resonance imaging (MRI) findings after successful microsurgical removal of lumbar disc herniation with repeated MRI examinations. Summary of Background Data. The interpretation of MRI after spinal surgery may be particularly challenging and image findings do not always correlate to clinical findings. Early postoperative MRI has limited value in the evaluation of patients after surgery for lumbar disc herniation. Methods. Prospective study of 30 successfully operated patients, which underwent 3.0 T MRI within 24 h after surgery for lumbar disc herniation and repeated at 6 weeks and 3 months postoperatively. Postoperative image findings (nerve root enhancement, nerve root thickening, displacement or compression of the nerve root, and residual mass size and signal) were assessed quantitatively. Inter-rater reliability was tested. Results. Inter-rater reliability between neuroradiologists was moderate for assessed MRI variables. In the immediate postoperative phase, compression or dislocation of the nerve root at the operated level was common. A residual mass at the operated level was seen in 80%, 47%, and 33% after 24 h, 6 weeks, and 3 months, respectively. Postoperative dislocation or compression of the nerve root from residual masses was seen in 67%, 24%, and 14% after 24 h, 6 weeks, and 3 months, respectively. A residual mass with a higher signal than muscle on T2-weighted images was seen in 80%, 30%, and 17% after 24 h, 6 weeks, and 3 months, respectively. Conclusion. A residual mass with compression or dislocation of the nerve root at the operated level, that disappears over 3 months, is a common MRI finding in patients successfully operated for symptomatic lumbar disc herniation. An expectant approach instead of early reoperations may perhaps be preferred in patients with residual pain and root compression due to residual masses with high T2-signal since these often seem to resolve spontaneously. Level of Evidence: 3

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Patient-Based Surgical Outcomes of Posterior Lumbar Interbody Fusion: Patient Satisfaction Analysis

Study Design. A retrospective study. Objective. The purpose of this study was to investigate: (1) patient-based surgical outcomes of posterior lumbar interbody fusion (PLIF); (2) correlations between patient-based surgical outcomes and surgeon-based surgical outcomes; (3) factors associated with patient satisfaction. Summary of Background Data. There have been no reports of patient-based surgical outcomes of PLIF for lumbar spondylolisthesis. Methods. Patients who underwent PLIF for L4 degenerative spondylolisthesis between 2006 and 2009 were reviewed (n = 121). Surgical outcomes were assessed 5 years after primary surgery using a questionnaire, a numerical rating scale (NRS) of pain, the 36-Item Short Form Health Survey (SF-36), the Japanese Orthopedic Association score (JOA score), and the recovery rate. The original questionnaire consisted of 5 categories, with scoring out of 100 points for surgery, satisfaction, improvement, recommendation to others, and willingness to undergo repeat surgery. Patient-based outcomes were divided into 3 groups according to the questionnaire responses as positive, intermediate, and negative and were compared with the JOA scores. Results. A total of 103 patients responded, for a response rate of 85%. The average patient-evaluated score for surgery was 82 points. The positive response rate in each category was 78% for satisfaction, 88% for improvement, 74% for recommendation, and 71% for repeat. The average pre- and postoperative JOA scores were 11.2 and 23.2, respectively. The average recovery rate was 68.5%. There were significant correlations between patient-based surgical outcomes and the JOA score. Furthermore, there were significant correlations between patient-based surgical outcomes and the NRS and physical component scores of the SF-36. Postoperative permanent motor loss was a major factor related to a negative response. Conclusion. The patient-evaluated score for surgery was 82 points. More than 70% of patients gave positive responses in all sections of the questionnaire. There were significant correlations between patient-based and surgeon-based surgical outcomes. Level of Evidence: 2

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Nonfusion Does Not Prevent Adjacent Segment Disease: Dynesys Long-term Outcomes With Minimum Five-year Follow-up

Study Design. Case series. Objective. The aim of this study was to determine the relationship between fusion and adjacent segment disease via Dynesys long-term outcomes. Summary of Background Data. Dynesys is a dynamic stabilization system meant to improve symptoms by stabilizing the spine without fusion and avoiding the development of adjacent segment disease. However, few studies have evaluated long-term outcomes. Methods. All patients were operated on with Dynesys from 2006 to 2009 by a single surgeon at a single institution. We prospectively collected 18 variables among the following categories: patient characteristics, comorbidities, surgical indications, and OR variables. We analyzed two primary endpoints: solid fusion on X-ray and clinical adjacent segment disease (ASD) both at 5 years. Secondary endpoints were time to fusion, time to ASD, reoperation, Oswestry disability index (ODI), and visual analogue scale (VAS) leg pain. We conducted a multivariate analysis via the random forest method. Mann-Whitney U test and Fisher exact test were then used to qualify relationship between variables. Results. We had 52 patients to review in the database. Eight had preexisting ASD. Mean follow-up was 92 months (median 87 months). Fifteen had ASD (29%) during follow-up at a mean 45 months (Median 35 months). Nine had a solid fusion (17%), 2 of which also had ASD. Mean time to fusion was 65 months (median 71 months). Differences in improvement of ODI (P = 0.005) and VAS leg pain (P = 0.002) were significant favoring patients without ASD. The multivariate analysis revealed four variables associated with ASD: prior ASD (OR 11.3, P = 0.005), neurological deficit (OR 8.5, P = 0.018), revision OR (OR 8.5, P = 0.018), and multilevel degeneration (OR 0.184, P = 0.026). No variable was associated with fusion. Conclusion. Dynesys was associated with a high rate of ASD over long-term follow-up despite maintaining a low fusion rate. Prior ASD was the strongest predictor of progressive ASD. Level of Evidence: 3

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Opioid Overdoses Continue to Climb

Fatal drug overdoses in the United States reached an all-time high in 2014, driven largely by heroin and prescription opioid pain reliever abuse. The CDC’s recent analysis of mortality data found that of the 47 055 drug overdose deaths in 2014, 61% involved opioids, a 14% increase from the previous year (Rudd RA et al. MMWR Morb Mortal Wkly Rep. 2016;64[50-51]:1378-1382).

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Resilience, Pain Interference and Upper-Limb Loss: Testing the Mediating Effects of Positive Emotion and Activity Restriction on Distress

Association between catechol-O-methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case–control study

Abstract

Background

Although polymorphisms of the catechol-O-methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single-nucleotide polymorphisms (SNP) and FM risk and symptom severity.

Methods

In total, 409 FM patients and 423 controls were enrolled. Alleles and genotypes at five positions [rs6269 (A>G), rs4633 (C>T), rs4818 (C>G), rs4680 (C>G) and rs165599 (A>G)] in the COMT gene were genotyped from peripheral blood DNA.

Results

Alleles and genotypes of the rs4818 COMT gene polymorphism were significantly associated with increased susceptibility to FM. The rs4818 GG genotype was more strongly associated with FM compared to the CC genotype (OR = 1.680, 95% CI: 1.057, 2.672, p = 0.027). Although allele and genotype frequencies did not differ among groups, the rs4633 CT genotype was not associated with the presence of FM following adjustment for age and sex (OR = 0.745; 95% CI: 0.558, 0.995; p = 0.046). However, no association was observed between clinical measures and individual COMT SNPs. In haplotype analysis, there was a significant association between ACG haplotype and FM susceptibility sex (OR = 2.960, 95% CI: 1.447, 6.056, p = 0.003) and the number of tender points (p = 0.046).

Conclusions

This large-scale study suggests that polymorphisms of the COMT gene may be associated with FM risk and pain sensitivity in Korean FM patients. However, our results differed to those of previous studies, suggesting ethnic variation in COMT gene polymorphisms in FM.

What does this study add

By contrast to Caucasian and Latin-American populations, the COMT gene polymorphisms are associated with FM risk and pain sensitivity in Korean FM patients, suggesting ethnic variation in COMT gene polymorphisms.

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Reviewer Acknowledgements

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Pain self-management training increases self-efficacy, self-management behaviours and pain and depression outcomes

Abstract

Background

Self-management practices among patients with medical and psychiatric comorbidity is not well understood. We assessed the effects of a combined pharmacological and behavioural intervention on self-efficacy to manage symptoms and self-management behaviours in patients with pain and comorbid depression.

Methods

Longitudinal analysis of self-management behaviours and their relationship with outcomes in a 12-month trial of 250 primary care patients with chronic musculoskeletal pain and comorbid depression. Participants were randomized to either usual care or an intervention that consisted of optimized antidepressant therapy followed by six sessions of a pain self-management (PSM) programme.

Results

Participants in the intervention group significantly increased the time spent performing self-management behaviours including strengthening and stretching exercises, progressive muscle relaxation and visualization at 12 months. Moreover, intervention participants reported greater self-efficacy to manage their pain and depression. The number of pain self-management sessions received showed a dose–response relationship with improvement in both pain and depression severity.

Conclusion

A combined intervention increased patient self-management behaviours and self-efficacy to manage symptoms among primary care patients with chronic musculoskeletal pain and depression. Receipt of the full dose of the entire PSM programme was related to improvements in pain interference and depression severity.

What does this study add?

A nurse-led six-session PSM programme increased self-efficacy as well as specific behaviours such as strengthening and stretching exercises, progressive muscle relaxation and visualization.

There was a dose–response in that attending a greater proportion of the PSM sessions led to greater improvement in both pain and depression outcomes.

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Neonatal developmental care in infant pain management and internalizing behaviours at 18 months in prematurely born children

Abstract

Background

Very preterm infants are exposed to adverse stressful experiences, which may result in long-term behavioural outcomes. The developmental care practices, including pain management and environmental support, can minimize the effects of stress exposure. However, developmental care quality levels may vary among Neonatal Intensive Care Units (NICUs) and little is known about how differences in developmental care quality affect long-term behavioural outcomes. The aim of this study was to examine the relation between quality levels NICUs developmental care and behaviour problems at 18 months corrected age in preterm children.

Methods

The behaviour of 134 preterm children from 22 NICUs and 123 full-term controls was examined using the questionnaire Child Behaviour Checklist 1½–5. We compared the behavioural profile of children by splitting NICUs into units with high- and low quality of developmental care according to two main care factors: (1) infant centered care (ICC) index, and (2) infant pain management (IPM) index.

Results

Preterm children from low-care units in IPM group reported higher scores in Internalizing Problems, compared to children from high-care units. No differences were found between preterm children from high-care in IPM and full-term children. No significant IPM effect was found for externalizing problems. No significant ICC effect emerged both for internalizing and externalizing problems.

Conclusions

Findings suggest that higher quality of developmental care related to infant pain management can mitigate behavioural problems at 18 months in children born preterm, to such an extent that preterm children exhibit a behavioural profile similar to that displayed by full-term children.

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Corrigendum

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Shared and Unique Mechanisms Underlying Binge Eating Disorder and Addictive Disorders

WHO analgesic ladder and chronic pain: the need to search for treatable causes

Ballantyne and colleagues’ important message on the overuse of opioids in treating chronic pain is long overdue.1 As they point out, opioids are usually ineffective and they have major potential...

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Well-Demarcated, Scaly Plaques

A 46-year-old woman presented with well-demarcated erythematous scaly plaques, with central clearing, on her chest, back, flanks, and groin. She reported that the eruption worsens with warmer weather but reported no other pain or rash. What would you do next?

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Abdominal pain in a 31 year old woman

A 31 year old white woman presented with recurrent abdominal pain and distention. A barium follow through examination was performed. What is the diagnosis?bmj;352/feb02_1/i524/FAF1faAnswerCongenital...

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The relationship between overactivity and opioid use in chronic pain: a 5-day observational study

Abstract: With increasing concerns about the potential harm of long-term opioid therapy, there is a need for the development and implementation of alternative treatment strategies for patients with chronic pain who have been using opioids for a prolonged period of time. Based on the findings from a recent qualitative investigation that suggested there may be a bidirectional association between opioid reliance and habitual overactivity behaviour (activity engagement that significantly exacerbates pain), this study was designed to quantitatively investigate the association between opioid use and habitual overactivity over a 5-day period in a group of chronic pain patients. Participants provided a list of their prescribed pain medication, completed a self-report measure of habitual overactivity, and then commenced 5 days of data collection. Data collection required participants to wear an activity monitor and to complete a diary that detailed their daily activities and the time at which they took medication. Individuals reporting higher levels of habitual overactivity were more likely to be prescribed opioids. In addition, higher levels of habitual overactivity were associated with more frequent pro re nata (“as needed”) opioid use over the 5 days, and with a discrepancy between the prescribed and actual oral morphine-equivalent daily dose, where more medication was taken than was prescribed. There was no predominant context for pro re nata use. The results of this study support the idea that habitual overactivity behaviour may play a role in the development of reliance on opioid medication and that such an association may provide a potential treatment target for opioid therapy rationalisation.

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