Age differences in the time-course and magnitude of changes in circulating neuropeptides following pain evocation in humans

This study tested the hypothesis that older adults would have a stronger response for substance P (facilitatory) but weaker response to β-endorphin (inhibitory), both in magnitude and time-course. Eight younger and 9 older adults underwent 3 experimental sessions using well-validated laboratory pain models: cold pressor task (CPT), contact heat pain (HP), and a non-painful control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, and 60-minutes post-stimuli administration.

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Brief intervention, physical exercise and cognitive behavioural group therapy for patients with chronic low back pain (The CINS trial)

Abstract

Background and Objective

Cognitive-behavioural treatments (CBT) and physical group exercise (PE) have both shown promising effects in reducing disability and increasing work participation among chronic low back pain (CLBP) patients. A brief cognitive intervention (BI) has previously been demonstrated to reduce work disability in CLBP. The aim of this study was to test if the effect of BI could be further increased by adding either group CBT or group PE.

Methods

A total of 214 patients, all sick listed 2–10 months due to CLBP, were randomized to BI (n = 99), BI + group CBT (n = 55) or BI + group PE (n = 60). Primary outcome was increased work participation at 12 months, whereas secondary outcomes included pain-related disability, subjective health complaints, anxiety, depression, coping and fear avoidance.

Results

There were no significant differences between the groups in work participation at 12 months follow-up (χ² = 1.15, p = 0.56). No significant differences were found on the secondary outcomes either, except for a statistically significant reduction (time by group) in pseudoneurology one domain of subjective health complaints (sleep problems, tiredness, dizziness, anxiety, depression, palpitation, heat flushes) (F_2,136 = 3.109, p = 0.048) and anxiety (F_2,143 = 4.899, p = 0.009) for the groups BI + group CBT and BI + group PE, compared to BI alone. However, these differences were not significant in post hoc analyses (Scheffé adjusted).

Conclusion

There was no support for an effect of the added group CBT or group PE treatments to a brief cognitive intervention in this study of patients on sick leave due to low back pain.

Significance

Our study demonstrates that treatments that previously were found to be effective and are included in most treatment guidelines, such as group cognitive-behavior therapy and exercise, were not effective in this given context compared to a brief, cognitive intervention. This implies that an optimized brief intervention is difficult to outperform in patients on sick leave due to low back pain.

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Validation of the Behavioural Observation Scale 3 for the evaluation of pain in adults

Abstract

Background

Many behavioural scales are available to assess pain but none are suitable for a quick evaluation of non-sedated and non-geriatric adults. The Behavioural Observation Scale 3 (BOS-3) is short, composed of five items. This study examined its feasibility and diagnostic performances.

Methods

Adult patients were included from medical and surgical departments of the University Hospital of Bordeaux. In a cross-sectional study, BOS-3 was compared to Numerical Rate Scale (NRS) with communicating patients (CP) and Behavioural Scale for the Elderly Person (ECPA2) with non-communicating patients (NCP). Each time, BOS-3 and reference scale were performed by an internal caregiver and an external expert.

Results

We included 447 patients: 395 communicating and 52 non-communicating. All patients were assessed by the BOS-3 and the reference test. All BOS-3 were carried out in less than one minute with only four missing data. Its reproducibility (ICC = 0.77 [95% CI 0.73–0.81] with CP and 0.93 [95% CI 0.89–0.97] with NCP) and its internal consistency (Cronbach α = 0.67 with CP and 0.70 with NCP) were good. In non-communicating patients, ROC analysis set a threshold at 3 on 10. Sensitivity was 0.87 [95% CI 0.77–0.96], specificity 0.97 [95% CI 0.93–1.00], positive predictive value 0.93 [95% CI 0.86–0.99] and negative predictive value 0.95 [95% CI 0.89–1.00]. In communicating patients, sensitivity decreased to 0.34 [95% CI 0.28–0.38] but specificity reached 0.96 [95% CI 0.94–0.98] and positive predictive value 0.75 [95% CI 0.70–0.79].

Conclusions

BOS-3 had good metrological properties in non-communicating adults. With communicating patients, a positive BOS-3 could be an additional tool to confirm pain, when underestimated on the NRS.

Significance

This study describes the diagnostic performances of a behavioral pain assessment scale designed for non-geriatric and non-sedated adults. The results show its validity in non-communicating patients and suggest its usefulness as an ancillary tool in communicating patients in whom simple numerical scales are often insufficient.

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Pneumoscrotum following computed tomography pneumocolon

A 79 year old man presented with three hours of sudden onset severe generalised abdominal pain five hours after undergoing computed tomography (CT) pneumocolon. Examination revealed normal...

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OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients

Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that both chronic cancer pain and high dose opioid use lead to mu-opioid receptor down-regulation. In this study we explore down-regulation of OPRM1, the mu-opioid receptor gene, as a mechanism f,or opioid tolerance in the setting of opioid use for cancer pain. We demonstrate in a cohort of 84 cancer patients that high dose opioid use correlates with OPRM1 hypermethylation in peripheral leukocytes of these patients.

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Fear of pain changes movement: Motor behaviour following the acquisition of pain-related fear

Abstract

Background

According to current fear-avoidance models, changes in motor behaviour (e.g. avoidance) are a key component in the development and maintenance of chronic pain complaints. Yet, experimental research assessing actual behavioural changes following painful events is relatively sparse. This study investigated the effects of pain anticipation on changes in motor behaviour using a fear conditioning paradigm and robot-generated standardized movement trajectories of the upper extremities.

Methods

Pain-free participants (N = 20) performed clockwise and counterclockwise fixed, circular movements with a robotic arm without receiving visual feedback. During fear acquisition, moving in one direction (CS+) was paired with a painful stimulus (pain-US) whereas moving in the other direction (CS−) was not. During the subsequent extinction phase, the pain-US was omitted. We assessed self-reported pain-related fear and urge to avoid the movement, as well as several behavioural measures: Velocity, acceleration, exerted force and force direction.

Results

Movements that were paired with pain were associated with increased self-reported pain-related fear and urge to avoid. Moreover, movements that were associated with pain were performed faster, more forcefully and more accurately than movements that were not associated with pain. All these differences diminished during the extinction phase.

Conclusions

The present study demonstrates the utility of robot-generated force feedback in the study of pain-related fear and associated changes in motor behaviour.

Significance

Fear of pain changes movement: Movements associated with pain are performed faster, with more force and higher accuracy than movements that are not associated with pain. These changes can inform us how fear of pain translates into avoidance and escape behaviour, two important constructs in the maintenance of chronic pain.

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Chronic stress-induced mechanical hyperalgesia is controlled by capsaicin-sensitive neurones in the mouse

Abstract

Background

Clinical studies demonstrated peripheral nociceptor deficit in stress-related chronic pain states, such as fibromyalgia. The interactions of stress and nociceptive systems have special relevance in chronic pain, but the underlying mechanisms including the role of specific nociceptor populations remain unknown. We investigated the role of capsaicin-sensitive neurones in chronic stress-related nociceptive changes.

Method

Capsaicin-sensitive neurones were desensitized by the capsaicin analogue resiniferatoxin (RTX) in CD1 mice. The effects of desensitization on chronic restraint stress (CRS)-induced responses were analysed using behavioural tests, chronic neuronal activity assessment in the central nervous system with FosB immunohistochemistry and peripheral cytokine concentration measurements.

Results

Chronic restraint stress induced mechanical and cold hypersensitivity and increased light preference in the light–dark box test. Open-field and tail suspension test activities were not altered. Adrenal weight increased, whereas thymus and body weights decreased in response to CRS. FosB immunopositivity increased in the insular cortex, dorsomedial hypothalamic and dorsal raphe nuclei, but not in the spinal cord dorsal horn after the CRS. CRS did not affect the cytokine concentrations of hindpaw tissues. Surprisingly, RTX pretreatment augmented stress-induced mechanical hyperalgesia, abolished light preference and selectively decreased the CRS-induced neuronal activation in the insular cortex. RTX pretreatment alone increased the basal noxious heat threshold without influencing the CRS-evoked cold hyperalgesia and augmented neuronal activation in the somatosensory cortex and interleukin-1α and RANTES production.

Conclusions

Chronic restraint stress induces hyperalgesia without major anxiety, depression-like behaviour or peripheral inflammatory changes. Increased stress-induced mechanical hypersensitivity in RTX-pretreated mice is presumably mediated by central mechanisms including cortical plastic changes.

Significance

These are the first data demonstrating the complex interactions between capsaicin-sensitive neurones and chronic stress and their impact on nociception. Capsaicin-sensitive neurones are protective against stress-induced mechanical hyperalgesia by influencing neuronal plasticity in the brain.

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Placebo Analgesia from a Rubber Hand

Placebo analgesia, reductions in pain following administration of an inert treatment, is a well-documented phenomenon. We report the first demonstration that placebo analgesia can be experienced when a sham analgesic is applied onto a rubber hand. The effect was obtained by exploiting the rubber hand illusion, in which ownership is felt over a rubber arm that is unattached to the body. Under conditions of both synchronous and asynchronous visuo-tactile stimulation, a thermal pain stimulus was delivered on the real arm of twenty participants and seemingly also on the rubber arm, before and after applying a sham analgesic and a control cream only to the rubber arm.

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Predictors of treatment outcome in contextual cognitive and behavioural therapies for chronic pain: a systematic review

There is increasing evidence that Contextual forms of Cognitive Behavioural Therapy (CBT) are effective in the management of chronic pain, yet little is understood about the factors that moderate or predict outcomes in these treatments. This systematic review aimed to identify pre-treatment participant characteristics associated with positive treatment responses in Contextual CBT for chronic pain. Medline, EMBASE, PsychINFO and CENTRAL were searched to identify eligible studies. Studies were included if the participants were adults with chronic pain, designs were longitudinal, treatments focused on psychological flexibility or mindfulness, and reported results allowed for examination of moderators or predictors of standard treatment outcomes.

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A longitudinal randomized trial of the impact of consistent pain management for infant vaccinations on future vaccination distress

The objective was to determine if consistent pain management during vaccine injections has a beneficial effect on future infant pain reactivity. This was a multicentre, longitudinal, double-blind, double-dummy, add-on, randomized controlled trial. Healthy infants were randomized to 1 of 4 add-on pain management regimens for all vaccinations in the first year of life: 1) placebo control (standard care); 2) parent video education about infant soothing (video); 3) video + oral sucrose solution (sucrose), 4) video + sucrose + topical liposomal lidocaine (lidocaine).

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Placebo Analgesia from a Rubber Hand

Placebo analgesia, reductions in pain following administration of an inert treatment, is a well-documented phenomenon. We report the first demonstration that placebo analgesia can be experienced when a sham analgesic is applied onto a rubber hand. The effect was obtained by exploiting the rubber hand illusion, in which ownership is felt over a rubber arm that is unattached to the body. Under conditions of both synchronous and asynchronous visuo-tactile stimulation, a thermal pain stimulus was delivered on the real arm of twenty participants and seemingly also on the rubber arm, before and after applying a sham analgesic and a control cream only to the rubber arm.

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Predictors of treatment outcome in contextual cognitive and behavioural therapies for chronic pain: a systematic review

There is increasing evidence that Contextual forms of Cognitive Behavioural Therapy (CBT) are effective in the management of chronic pain, yet little is understood about the factors that moderate or predict outcomes in these treatments. This systematic review aimed to identify pre-treatment participant characteristics associated with positive treatment responses in Contextual CBT for chronic pain. Medline, EMBASE, PsychINFO and CENTRAL were searched to identify eligible studies. Studies were included if the participants were adults with chronic pain, designs were longitudinal, treatments focused on psychological flexibility or mindfulness, and reported results allowed for examination of moderators or predictors of standard treatment outcomes.

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A longitudinal randomized trial of the impact of consistent pain management for infant vaccinations on future vaccination distress

The objective was to determine if consistent pain management during vaccine injections has a beneficial effect on future infant pain reactivity. This was a multicentre, longitudinal, double-blind, double-dummy, add-on, randomized controlled trial. Healthy infants were randomized to 1 of 4 add-on pain management regimens for all vaccinations in the first year of life: 1) placebo control (standard care); 2) parent video education about infant soothing (video); 3) video + oral sucrose solution (sucrose), 4) video + sucrose + topical liposomal lidocaine (lidocaine).

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Role of transcranial direct current stimulation on reduction of postsurgical opioid consumption and pain in total knee arthroplasty: Double randomized clinical trial

Abstract

Background

Postoperative pain control is an important factor in determining recovery in total knee arthroplasty (TKA).The aim of the study was to assess the efficacy of 4 sessions of transcranial direct current stimulation (tDCS) over primary motor cortex (M1) in patients undergoing unilateral TKA.

Materials

Fifty patients undergoing TKA were included in the study. They were divided randomly into two groups (25 patients for each, using closed envelopes): real tDCS (2 mA, 20 min, with anodal stimulation applied over M1 postoperative for 4 consecutive days) and sham tDCS. Opioid consumption was titrated by an anaesthesiologist during the study period and was used as primary outcome. As a secondary outcome, patients were evaluated using Visual Analogue Scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS) at baseline, then the 1st, 2nd, 3rd and 4th days after operation.

Results

There was no significant difference between real and sham tDCS in any rating scales at baseline. The opioid consumption and LANSS scores decreased more in patients who received real tDCS over the course of the treatment than sham tDCS. Real tDCS was associated with 59% reduction in the titrated analgesia. There was no significant difference between groups (time × groups interaction) in the VAS.

Conclusion

Since the VAS was constant, repeated sessions of anodal tDCS over M1 with an extra-cephalic cathodal electrode can achieve the same degree of analgesia with less opioid consumption over the postoperative days after TKA. Thus, tDCS is a promising tool in the field of postoperative analgesia.

Significance

The data of the present study suggest that four sessions of transcranial direct current brain stimulation over motor cortex could reduce morphine consumption and pain perception during the postoperative period in total knee arthroplasty.

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Differential effect of Incobotulinumtoxin A on pain, neurogenic flare and hyperalgesia in human surrogate models of neurogenic pain

Abstract

Background

The effectiveness of Botulinum-neurotoxin A (BoNT/A) to treat pain in human pain models is very divergent. This study was conducted to clarify if the pain models or the route of BoNT/A application might be responsible for these divergent findings.

Methods

Sixteen healthy subjects (8 males, mean age 27 ± 5 years) were included in a first set of experiments consisting of three visits: (1) Visit: Quantitative sensory testing (QST) was performed before and after intradermal capsaicin injection (CAPS, 15 μg) on one thigh and electrical current stimulation (ES, 1 Hz) on the contralateral thigh. During stimulation pain and the neurogenic flare response (laser-Doppler imaging) were assessed. (2) Four weeks later, BoNT/A (Xeomin^®, 25 MU) was injected intracutaneously on both sides. (3) Seven days later, the area of BoNT/A application was determined by the iodine-starch staining and the procedure of the (1) visit was exactly repeated. In consequence of these results, 8 healthy subjects (4 males, mean age 26 ± 3 years) were included into a second set of experiments. The experimental setting was exactly the same with the exception that stimulation frequency of ES was increased to 4 Hz and BoNT/A was injected subcutaneously into the thigh, which was stimulated by capsaicin.

Results

BoNT/A reduced the 1 Hz ES flare size (p < 0.001) and pain ratings (p < 0.01), but had no effect on 4 Hz ES and capsaicin-induced pain, hyperalgesia, or flare size, regardless of the depth of BoNT/A injection (i.c./s.c). Moreover, i.c. BoNT/A injection significantly increased warm detection and heat pain thresholds in naive skin (WDT, Δ 2.2 °C, p < 0.001; HPT Δ 1.8 °C, p < 0.005).

Conclusion

BoNT/A has a moderate inhibitory effect on peptidergic and thermal C-fibers in healthy human skin.

Significance

The study demonstrates that BoNT/A (Incobotulinumtoxin A) has differential effects in human pain models: It reduces the neurogenic flare and had a moderate analgesic effects in low frequency but not high frequency current stimulation of cutaneous afferent fibers at C-fiber strength; BoNT/A had no effect in capsaicin-induced (CAPS) neurogenic flare or pain, or on hyperalgesia to mechanical or heat stimuli in both pain models. Intracutaneous BoNT/A increases warm and heat pain thresholds on naïve skin.

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Treating low back pain with combined cerebral and peripheral electrical stimulation: A randomized, double-blind, factorial clinical trial

Abstract

Background

Recent evidence suggests that chronic low back pain is associated with plastic changes in the brain that can be modified by neuromodulation strategies. This study investigated the efficacy of transcranial direct current stimulation (tDCS) combined simultaneously with peripheral electrical stimulation (PES) for pain relief, disability and global perception in patients with chronic low back pain (CLBP).

Methods

Ninety-two patients with CLBP were randomized to receive 12 sessions on nonconsecutive days of anodal tDCS (primary motor cortex, M1), 100 Hz sensory PES (lumbar spine), tDCS + PES or sham tDCS + PES. Pain intensity (11-point numerical rating scale), disability and global perception were applied before treatment and four weeks, three months and six months post randomization.

Results

A two points reduction was achieved only by the tDCS + PES (mean reduction [MR] = −2.6, CI95% = −4.4 to −0.9) and PES alone (MR = −2.2, CI95% = −3.9 to −0.4) compared with the sham group, but not of tDCS alone (MR = −1.7, CI95% = −3.4 to −0.0). In addition to maintaining the analgesic effect for up to three months, tDCS + PES had a higher proportion of respondents in different cutoff points. Global perception was improved at four weeks and maintained three months after treatment only with tDCS + PES. None of the treatments improved disability and the affective aspect of pain consistently with pain reduction.

Conclusion

The results suggest that tDCS + PES and PES alone are effective in relieving CLBP in the short term. However, only tDCS + PES induced a long-lasting analgesic effect. tDCS alone showed no clinical meaningful pain relief.

Significance

Transcranial direct current stimulation combined simultaneously with PES leads to a significant and clinical pain relief that can last up to three months in chronic low back pain patients.

For this article, a commentary is available at the Wiley Online Library

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Management of chronic pain using complementary and integrative medicine

Complementary and integrative medicine (CIM) encompasses both Western-style medicine and complementary health approaches as a new combined approach to treat a variety of clinical conditions. Chronic...

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Neural correlates of evoked phantom limb sensations

Capsule-Preserving Hydrodilatation With Corticosteroid Versus Corticosteroid Injection Alone in Refractory Adhesive Capsulitis of Shoulder: A Randomized Controlled Trial

Myofascial Induction Effects on Neck-Shoulder Pain in Breast Cancer Survivors: Randomized, Single-Blind, Placebo-Controlled Crossover Design

Effectiveness of an Educational Physiotherapy and Therapeutic Exercise Program in Adult Patients With Hemophilia

Living With Chronic Pain After Spinal Cord Injury: A Mixed-Methods Study

Content and Evaluation of the Benefits of Effective Exercise for Older Adults With Knee Pain Trial Physiotherapist Training Program

Polydeoxyribonucleotide Injection in the Treatment of Chronic Supraspinatus Tendinopathy

Relation Between Subacromial Bursitis on Ultrasonography and Efficacy of Subacromial Corticosteroid Injection in Rotator Cuff Disease: A Prospective Comparison Study

Effect of Unmodulated 5-kHz Alternating Currents Versus Transcutaneous Electrical Nerve Stimulation on Mechanical and Thermal Pain, Tactile Threshold, and Peripheral Nerve Conduction: A Double-Blind, Placebo-Controlled Crossover Trial

Functional Goals and Predictors of Their Attainment in Low-Income Community-Dwelling Older Adults

Percutaneous Needle Tenotomy for the Treatment of Muscle and Tendon Contractures in Adults With Brain Damage: Results and Complications

Effect of a Single Administration of Focused Extracorporeal Shock Wave in the Relief of Delayed-Onset Muscle Soreness: Results of a Partially Blinded Randomized Controlled Trial

Efficacy of Combined Ultrasound-Guided Steroid Injection and Splinting in Patients With Carpal Tunnel Syndrome

Botulinum Toxin Treatment for Nocturnal Calf Cramps in Patients With Lumbar Spinal Stenosis: A Randomized Clinical Trial

Ultrasound-Guided Pulsed Radiofrequency Stimulation of Posterior Tibial Nerve: A Potential Novel Intervention for Recalcitrant Plantar Fasciitis

Physical Activity After a Hip Fracture: Effect of a Multicomponent Home-Based Rehabilitation Program—A Secondary Analysis of a Randomized Controlled Trial

Ottawa Panel Evidence-Based Clinical Practice Guidelines for Structured Physical Activity in the Management of Juvenile Idiopathic Arthritis

Effectiveness of 3 Weekly Injections Compared With 5 Weekly Injections of Intra-Articular Sodium Hyaluronate on Pain Relief of Knee Osteoarthritis or 3 Weekly Injections of Other Hyaluronan Products: A Systematic Review and Meta-Analysis

One-Level Lumbar Degenerative Spondylolisthesis and Posterior Approach: Is Transforaminal Lateral Interbody Fusion Mandatory?: A Randomized Controlled Trial With 2-Year Follow-Up

Study Design. A monocentric open-label randomized controlled trial (MRCT). Objective. Comparison of clinical and radiological outcomes between isolated instrumented posterior fusion (PLF) and associated instrumented posterior fusion and interbody fusion by transforaminal approach (PLF + TLIF) for patients suffering from one-level lumbar degenerative spondylolisthesis (DS) undergoing surgery. Summary of Background Data. DS is a common cause of symptomatic lumbar stenosis. PLF has shown better clinical outcome than decompression with noninstrumented posterolateral fusion. TLIF with interbody cage showed better fusion rate than PLF. There is a need for randomized controlled trials to compare PLF with and without TLIF as to clinical and radiological outcomes. Methods. This is a MRCT comparing PLF and TLIF techniques in surgical treatment of DS. Sixty patients were included in a secured database from 2009 to 2011 and randomized into two groups: 30 PLF with posterior pedicle screws and intertransverse autologuous graft, and 30 TLIF in which an interbody fusion by transforaminal approach was added. Data included clinical (pain and disability), surgical (blood loss and operating time), and radiological (alignment and fusion) parameters at baseline and 2-year follow-up. Comparison was made by Student t test and Chi-square test. Results. There was a significant improvement in each group for pain and disability but no difference between the groups. Radiographic assessment showed better posterolateral fusion rate for TLIF without superiority in segmental lordosis improvement. A case of deformity cascade with spino-pelvic mismatch at baseline was noted in PLF. Conclusion. Posterior decompression and instrumented fusion is an efficient technique that proved its significant clinical benefit in the surgical treatment of DS. TLIF did not show its superiority neither in clinical nor alignment parameters despite a better fusion rate. These results suggest that TLIF is not mandatory in this specific indication. Sagittal alignment analysis by standing full-body images should be considered in DS care. Level of Evidence: 2

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Anterior Cervical Discectomy and Fusion Provides Better Surgical Outcomes Than Posterior Laminoplasty in Elderly Patients With C3-4 Level Myelopathy

Study Design. Retrospective analyses of prospectively collected data regarding 180 patients with cervical spondylotic myelopathy (CSM). Objective. To detect the characteristics of C3-4 level CSM in elderly patients (C3-4CSM) (main analysis) and to validate the postoperative outcomes of anterior cervical discectomy and fusion (ACDF) and of laminoplasty (LAMP) (subgroup analysis). Summary of Background Data. It remains unclear which surgical technique offers the best outcomes for CSM. Methods. The main analysis included 180 patients with CSM, divided into two groups (C3-4CSM group, n = 46; conventional CSM group, n = 134) according to the findings of the preoperative physical examination and magnetic resonance imaging. The subgroup analysis included 46 patients with C3-4CSM, divided into two groups (ACDF group, n = 21; LAMP group, n = 25) according to surgical technique. Preoperative demographics and postoperative outcomes were compared. Results. The age at surgery was higher, disease duration was shorter, and preoperative Japanese Orthopaedic Association (JOA) score was lower in the C3-4CSM group than in the conventional CSM group. Although the C3-4 range of motion was significantly higher, that of other levels was significantly lower in the C3-4CSM group. The anteroposterior diameter for levels C3-C7 was significantly larger in the C3-4CSM group. In the subgroup analysis using the repeated-measures analysis of variance, the postoperative JOA scores, and visual analog scale of neck pain were significantly better in the ACDF group. Conclusion. Higher age, shorter disease duration, and worse JOA scores appear to be characteristic of C3-4CSM. In the management of C3-4CSM, ACDF provided better surgical outcomes than did LAMP; hypermobility at the C3-4 level, a radiological characteristic of C3-4CSM, may be one of key factors affecting surgical outcome. The chance to diagnose C3-4CSM is increasing with the increasing healthy life expectancy. To enable effective resolution of symptoms, C3-4CSM must be distinguished from conventional CSM. Level of Evidence: 4

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Nonsteroidal Anti-inflammatory Drugs for Sciatica: An Updated Cochrane Review

Study Design. Systematic review and meta-analysis. Objective. To determine the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on pain reduction, overall improvement, and reported adverse effects in people with sciatica. Summary of Background Data. NSAIDs are one of the most frequently prescribed drugs for sciatica. Methods. We updated a 2008 Cochrane Review through June 2015. Randomized controlled trials that compared NSAIDs with placebo, with other NSAIDs, or with other medication were included. Outcomes included pain using mean difference (MD, 95% confidence intervals [95% CI]). For global improvement and adverse effects risk ratios (RR, 95% CI) were used. We assessed level of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Results. Ten trials were included (N = 1651). Nine out of 10 trials were assessed at high risk of bias. For pain reduction (visual analog scale, 0 to 100) NSAIDs were no more effective than placebo (MD −4.56, 95% CI −11.11 to 1.99, quality of evidence: very low). For global improvement NSAIDs were more effective than placebo (RR 1.14 [95% CI 1.03 to 1.27], low quality of evidence). One trial reported the effect of NSAIDs on disability with very low-quality evidence that NSAIDs are no more effective than placebo. There was low-quality evidence that the risk for adverse effects is higher for NSAID than placebo (RR 1.40, 95% CI 1.02 to 1.93). Conclusion. Our findings show very low-quality evidence that the efficacy of NSAIDs for pain reduction is comparable with that of placebo, low-quality evidence that NSAIDs is better than placebo for global improvement and low-quality evidence for higher risk of adverse effects using NSAIDs compared with placebo. The findings must be interpreted with caution, due to small study samples, inconsistent results, and a high risk of bias in the included trials. Level of Evidence: 1

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Minimum Clinically Important Difference and Substantial Clinical Benefit in Pain, Functional, and Quality of Life Scales in Failed Back Surgery Syndrome Patients

Study Design.. Prospective observational 1-year study. Objective.. To determine minimum clinically important difference (MCID) and substantial clinical benefit (SCB) of outcome measures in failed back surgery syndrome (FBSS) patients, as these metrics enable assessment of whether and when an intervention produces clinically meaningful effects in a patient. Summary of Background Data.. Several methods have been devised to quantify clinically important difference, but MCID and SCB for FBSS patients has yet to be determined. Methods.. Patients with persisting/recurrent low back pain (LBP) and/or leg pain after lumbar surgery who completed 16 weeks of treatment (n = 105) at two hospitals in Korea from November 2011 to September 2014 were analyzed. Global perceived effect was used to determine receiver operating characteristic curves in visual analogue scale (VAS), Oswestry disability index (ODI), and short form-36 (SF-36) in an anchor-based approach. Results.. MCIDs for ODI, LBP and leg pain VAS, physical component summary, mental health component summary (MCS), and overall health scores of SF-36 were 9.0, 22.5, 27.5, 10.2, 4.0, and 8.9, and SCBs were 15.0, 32.5, 37.0, 19.7, 19.3, and 21.1, respectively. MCID and SCB area under the curve was ≥0.8, and ≥0.7, respectively. Conclusion.. LBP and leg pain VAS, ODI, and physical component summary of SF-36 may be used to measure responsiveness in FBSS patients. Level of Evidence: 3

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Contribution of Lumbar Spine Pathology and Age to Paraspinal Muscle Size and Fatty Infiltration

Study Design. Retrospective chart analysis of 199 individuals aged 18 to 80 years scheduled for lumbar spine surgery. Objective. The purpose of this study was to quantify changes in muscle cross-sectional area (CSA) and fat signal fraction (FSF) with age in men and women with lumbar spine pathology and compare them to published normative data. Summary of Background Data. Pathological changes in lumbar paraspinal muscle are often confounded by age-related decline in muscle size (CSA) and quality (fatty infiltration). Individuals with pathology have been shown to have decreased CSA and fatty infiltration of both the multifidus and erector spinae muscles, but the magnitude of these changes in the context of normal aging is unknown. Methods. Individuals aged 18 to 80 years who were scheduled for lumbar surgery for diagnoses associated with lumbar spine pain or pathology were included. Muscle CSA and FSF of the multifidus and erector spinae were measured from preoperative T2-weighted magnetic resonance images at the L4 level. Univariate and multiple linear regression analyses were performed for each outcome using age and sex as predictor variables. Statistical comparisons of univariate regression parameters (slope and intercept) to published normative data were also performed. Results. There was no change in CSA with age in either sex (P > 0.05), but women had lower CSAs than men in both muscles (P < 0.0001). There was an increase in FSF with age in erector spinae and multifidus muscles in both sexes (P < 0.0001). Multifidus FSF values were higher in women with lumbar spine pathology than published values for healthy controls (P = 0.03), and slopes tended to be steeper with pathology for both muscles in women (P < 0.08) but not in men (P > 0.31). Conclusion. Lumbar muscle fat content, but not CSA, changes with age in individuals with pathology. In women, this increase is more profound than age-related increases in healthy individuals. Level of Evidence: 3

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Impact of the Opioid Safety Initiative on opioid-related prescribing in veterans

Abstract: The Veterans Health Administration (VHA) designed the Opioid Safety Initiative (OSI) to help decrease opioid prescribing practices associated with adverse outcomes. Key components included disseminating a dashboard tool that aggregates electronic medical record data to audit real-time opioid-related prescribing and identifying a clinical leader at each facility to implement the tool and promote safer prescribing. This study examines changes associated with OSI implementation in October 2013 among all adult VHA patients who filled outpatient opioid prescriptions. Interrupted time series analyses controlled for baseline trends and examined data from October 2012 to September 2014 to determine the changes after OSI implementation in prescribing of high-dosage opioid regimens (total daily dosages >100 morphine equivalents [MEQ] and >200 MEQ) and concurrent benzodiazepines. Across VHA facilities nationwide, there was a decreasing trend in high-dosage opioid prescribing with 55,722 patients receiving daily opioid dosages >100 MEQ in October 2012, which decreased to 46,780 in September 2014 (16% reduction). The OSI was associated with an additional decrease, compared to pre-OSI trends, of 331 patients per month (95% confidence interval [CI] −378 to −284) receiving opioids >100 MEQ, a decrease of 164 patients per month (95% CI −186 to −142) receiving opioids >200 MEQ, and a decrease of 781 patients per month (95% CI −969 to −593) receiving concurrent benzodiazepines. Implementation of a national health care system-wide initiative was associated with reductions in outpatient prescribing of risky opioid regimens. These findings provide evidence for the potential utility of large-scale interventions to promote safer opioid prescribing.

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Spinal cord interneurons expressing the gastrin-releasing peptide receptor convey itch through VGLUT2-mediated signaling

Abstract: Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli. In the spinal cord, neurons expressing the gastrin-releasing peptide receptor (GRPR) have been identified as specific mediators of itch. However, our understanding of the GRPR population in the spinal cord, and thus how these neurons exercise their functions, is limited. For this purpose, we constructed a Cre line designed to target the GRPR population of neurons (Grpr-Cre). Our analysis revealed that Grpr-Cre cells in the spinal cord are predominantly excitatory interneurons that are found in the dorsal lamina, especially in laminae II-IV. Application of the specific agonist gastrin-releasing peptide induced spike responses in 43.3% of the patched Grpr-Cre neurons, where the majority of the cells displayed a tonic firing property. Additionally, our analysis showed that the Grpr-Cre population expresses Vglut2 mRNA, and mice ablated of Vglut2 in Grpr-Cre cells (Vglut2-lox;Grpr-Cre mice) displayed less spontaneous itch and attenuated responses to both histaminergic and nonhistaminergic agents. We could also show that application of the itch-inducing peptide, natriuretic polypeptide B, induces calcium influx in a subpopulation of Grpr-Cre neurons. To summarize, our data indicate that the Grpr-Cre spinal cord neural population is composed of interneurons that use VGLUT2-mediated signaling for transmitting chemical and spontaneous itch stimuli to the next, currently unknown, neurons in the labeled line of itch.

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Placebo-like analgesia via response imagery

Abstract

Background

Placebo effects on pain are reliably observed in the literature. A core mechanism of these effects is response expectancies. Response expectancies can be formed by instructions, prior experiences and observation of others. Whether mental imagery of a response can also induce placebo-like expectancy effects on pain has not yet been studied systematically.

Methods

In Study 1, 80 healthy participants were randomly allocated to (i) response imagery or (ii) control imagery. In Study 2, 135 healthy participants were randomly allocated to (i) response imagery with a verbal suggestion regarding its effectiveness, (ii) response imagery only, or (iii) no intervention. In both studies, expected and experienced pain during cold pressor tests were measured pre- and post-intervention, along with psychological and physiological measures.

Results

Participants rated pain as less intense after response imagery than after control imagery in Study 1 (p = 0.044,  = 0.054) and as less intense after response imagery (with or without verbal suggestion) than after no imagery in Study 2 (p < 0.001,  = 0.154). Adding a verbal suggestion did not affect pain (p = 0.068,  = 0.038). The effects of response imagery on experienced pain were mediated by expected pain.

Conclusions

Thus, in line with research on placebo effects, the current findings indicate that response imagery can induce analgesia, via its effects on response expectancies.

Significance

The reported studies extend research on placebo effects by demonstrating that mental imagery of reduced pain can induce placebo-like expectancy effects on pain.

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Characterization of the effects of L-4-chlorokynurenine on nociception in rodents

Upon systemic administration in rats, the prodrug L-4-chlorokynurenine (4-Cl-KYN) (AV-101) is rapidly absorbed, actively transported across the blood-brain barrier, and converted in astrocytes to 7-chlorokynurenic acid (7-Cl-KYNA), a potent and specific antagonist of the GlyB co-agonist site of the NMDA receptor. We examined the effects of 4-Cl-KYN in several rat models of hyperalgesia and allodynia and determined the concentrations of 4-Cl-KYN and newly produced 7-Cl-KYNA in serum, brain and spinal cord.

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Validation of the Pain Resilience Scale in a Chronic Pain Sample

Psychosocial factors that protect against negative outcomes for individuals with chronic pain have received increased attention in recent years. Pain resilience, or the ability to maintain behavioral engagement and regulate emotions as well as cognitions despite prolonged or intense pain, is one such factor. A measure of pain-specific resilience, the Pain Resilience Scale, was previously identified as a better predictor of acute pain tolerance than general resilience. The present study sought to validate this measure in a chronic pain sample, while also furthering understanding of the role of pain resilience when compared to other protective factors.

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Migraine prevention using different frequencies of transcutaneous occipital nerve stimulation: A randomized controlled trial

To evaluate the efficacy and tolerability of transcutaneous occipital nerve stimulation (tONS) in patients with migraine, and to explore whether different tONS frequencies influenced treatment effectiveness.

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Long-term deterioration of perceived health and functioning in adults with cerebral palsy

Adult attachment insecurity is positively associated with medically unexplained chronic pain

Abstract

Background

Attachment insecurity (i.e. anxiety in relationships and/or discomfort in close relationships) is associated with self-reports of physical symptoms, medically unexplained symptoms and health conditions involving pain. Medically unexplained chronic pain (MUCP) may represent a particularly severe form of symptom reporting that is also characteristic of individuals with insecure attachment. This study investigated relationships between adult attachment style ratings and past-year MUCP in a sample of the general U.S. population and the ability of attachment style ratings to account for variance in past-year MUCP beyond that accounted for by potential confounders.

Method

Data from the National Comorbidity Survey Replication (N = 5645) were used. Attachment was assessed with an interview-administered version of a commonly used self-report measure of secure, anxious and avoidant attachment. MUCP was assessed with a brief interview. Depressive and anxiety disorders were included as covariates and were assessed with a fully structured interview based on DSM-IV criteria.

Results

The past-year prevalence of MUCP was 2.45% (95% CI = 2.07–2.83). The two insecure attachment styles (i.e. anxious and avoidant) were positively associated with MUCP. These associations remained statistically significant after adjusting for demographic variables and depressive and anxiety disorders. When the two insecure attachment styles were considered together, only avoidant attachment remained significantly associated with MUCP.

Conclusion

Attachment insecurity ratings were positively associated with past-year MUCP and remained so after statistically adjusting for depressive and anxiety disorders. Further research aimed at understanding the mechanism(s) responsible for the association between attachment insecurity and MUCP is warranted.

Significance

Consistent with earlier research regarding transient physical symptoms, medically unexplained chronic pain was associated with attachment insecurity. Understanding the mechanisms responsible for this association could guide treatment innovations.

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Analgesic effect of clobazam in chronic low-back pain but not in experimentally induced pain

Abstract

Background

Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests.

Methods

In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0–10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake.

Results

Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed.

Conclusions

This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds.

Significance

Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target.

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Pain thresholds, supra-threshold pain and lidocaine sensitivity in patients with erythromelalgia, including the I848Tmutation in NaV 1.7

Abstract

Objectives

Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM).

Methods

Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity.

Results

Heat pain thresholds and pain ratings to supra-threshold heat stimulation did not differ between EM-patients (n = 27) and controls (n = 25), neither did the dose–response curves for lidocaine. Only the subgroup of EM-patients with mutations in sodium channel subunits Na_V1.7, 1.8 or 1.9 (n = 8) had increased lidocaine sensitivity for supra-threshold heat stimuli, contrasting lower sensitivity to strong mechanical stimuli. This pattern was particularly clear in the two patients carrying the Na_V 1.7 I848T mutations in whom lidocaine's hyperalgesic effect on mechanical pain sensitivity contrasted more effective heat analgesia.

Conclusion

Heat pain thresholds are not sensitized in EM patients, even in those with gain-of-function mutations in Na_V1.7. Differential lidocaine sensitivity was overt only for noxious stimuli in the supra-threshold range suggesting that sensitized supra-threshold encoding is important for the clinical pain phenotype in EM in addition to lower activation threshold. Intracutaneous lidocaine dose-dependently blocked nociceptive sensations, but we did not identify EM patients with particular high lidocaine sensitivity that could have provided valuable therapeutic guidance.

Significance

Acute pain thresholds and supra-threshold heat pain in controls and patients with erythromelalgia do not differ and have the same lidocaine sensitivity. Acute heat pain thresholds even in EM patients with the Na_V 1.7 I848T mutation are normal and only nociceptor sensitivity to intradermal lidocaine is changed. Only in EM patients with mutations in Na_V 1.7, 1.8 or 1.9 supra-threshold heat and mechanical pain shows differential lidocaine sensitivity as compared to controls.

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Motivational and behavioural models of change: A longitudinal analysis of change among men with chronic haemophilia-related joint pain

Abstract

Background

Motivational and behavioural models of adjustment to chronic pain make different predictions about change processes, which can be tested in longitudinal analyses.

Methods

We examined changes in motivation, coping and acceptance among 78 men with chronic haemophilia-related joint pain. Using cross-lagged regression analyses of changes from baseline to 6 months as predictors of changes from 6 to 12 months, with supplementary structural equation modelling, we tested two models in which motivational changes influence behavioural changes, and one in which behavioural changes influence motivational changes.

Results

Changes in motivation to self-manage pain influenced later changes in pain coping, consistent with the motivational model of pain self-management, and also influenced later changes in activity engagement, the behavioural component of pain acceptance. Changes in activity engagement influenced later changes in pain willingness, consistent with the behavioural model of pain acceptance.

Conclusions

Based on the findings, a combined model of changes in pain self-management and acceptance is proposed, which could guide combined interventions based on theories of motivation, coping and acceptance in chronic pain.

Significance

This study adds longitudinal evidence about sequential change processes; a test of the motivational model of pain self-management; and tests of behavioural versus motivational models of pain acceptance.

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[Perspectives] The headache in history and culture

In 1964, author and critic Susan Sontag published a little-known short story entitled Man With a Pain. It is an eloquent reflection not only on the difficulties patients face when attempting to communicate “invisible” forms of pain to others, but also on the struggle that witnesses to their suffering experience in expressing sympathy.

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Characteristics and Factors Associated with Pain in Older Homeless Individuals: Results from the HOPE HOME Study

Individuals experiencing homelessness in the United States are aging; little is known about chronic pain in this population. In a cross-sectional, population-based study, we interviewed 350 homeless individuals aged 50 and older to describe pain experienced by older persons experiencing homelessness and to assess factors associated with chronic moderate to severe pain, defined as pain lasting ≥3 months, with a past week average severity score of 5-10 (scale 0-10). The median age of participants was 58 years.

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Issue Information

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In Memoriam Ulf Lindblom 1927–2017

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Spinal manipulation produces modest improvements in acute low back pain

Spinal manipulation therapy for acute low back pain is associated with modest improvements in pain and function, according to a systematic review and meta-analysis published in JAMA.1The authors said...

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Comparative effectiveness of non-operative treatments for chronic calcific tendinitis of the shoulder: A systematic review and network meta-analysis of randomized-controlled trials

Effectiveness of Physiotherapy intervention plus Extrinsic Feedback for neck disorders: A systematic review with meta-analysis

To systematically review the effectiveness of Physiotherapy interventions combined with extrinsic feedback (EF) compared to Physiotherapy intervention alone or control for the management of neck pain and disability.

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The dorsolateral prefrontal cortex in acute and chronic pain

The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous region and a key node of several brain networks, implicated in cognitive, affective, and sensory processing. As such, the DLPFC is commonly activated in experimental pain studies, and shows abnormally increased function in chronic pain populations. Furthermore, several studies have shown that some chronic pains are associated with decreased left DLPFC gray matter and that successful interventions can reverse this structural abnormality.

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Long term effects of repeated injections of local anesthetic with or without corticosteroid for lumbar spinal stenosis: a randomized trial

Examining affective-motivational dynamics and behavioural implications within the interpersonal context of pain

Emotional, motivational, and interpersonal dimensions are considered integral to pain experience but have largely been examined separately. In this focus article, we argue that an integrative theoretical account that acknowledges each of these elements is a critical next step to capture the complexity and nuance of interpersonal pain dynamics and to shape future research. The aim of this focus article is to provide a foundation for such an account by drawing upon established insights from appraisal theory of emotion, influential behavioral models, empathy/interpersonal pain research, and social psychology literature to highlight conceptual relationships, potential mechanisms of action, and avenues of inquiry that have not previously been examined in the context of pain.

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Minocycline prevents muscular pain hypersensitivity and cutaneous allodynia produced by repeated intramuscular injections of hypertonic saline in healthy human participants

Minocycline, a glial suppressor, prevents behavioural hypersensitivities in animal models of peripheral nerve injury. However clinical trials of minocycline in human studies have produced mixed results. This study addressed two questions: can repeated injections of hypertonic saline (HS) in humans induce persistent hypersensitivity? Can pre-treatment with minocycline, a tetracycline antibiotic with microglial inhibitory effects, prevent the onset of hypersensitivity? Twenty seven healthy participants took part in this double-blind, placebo-controlled study, consisting of six test sessions across 2 weeks.

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Preliminary Investigation of Pain-related Changes in Cerebral Blood Volume in Patients with Phantom Limb Pain

Reply to the Letter to the Editor Regarding 'Clinical assessment of subacromial shoulder impingement - Which factors differ from the asymptomatic population?'

Thank you for your comments regarding the recent publication ‘Clinical Assessment of Subacromial Shoulder Impingement – Which Factors Differ from the Asymptomatic Population?’ Not surprisingly, impingement is a term which does not reflect the underlying cause of all shoulder pain. Hence there is healthy debate, especially amongst physical therapists, regarding alternate terminology (Braman, Zhao, Lawrence, Harrison, & Ludewig, 2013; J. S. Lewis, 2011; McFarland et al., 2013). However, it continues to be a term used throughout the medical literature and in an attempt to embrace this wider audience, until there is agreement about terminology, it was chosen for use in this paper.

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[Perspectives] Illness as a philosophical tool

When once I was bed-bound with back pain, I reached for the words of another invalid, Marcel Proust, and began to make headway with his experience of “lost time”. Recovering 6 months later, I had not come to the end of Remembrance of Things Past, but I had learned that the minutiae of everyday lived experience can have their own fascination (even if Proust never quite addressed his own asthma directly). This approach to life resonates with philosopher Havi Carel's book Phenomenology of Illness. Carel laments that philosophers, traditionally men, neglect a high proportion of what matters to people—love, family, children, ageing, and illness.

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Abdominal pain after surgery

A 24 year old woman presented with acute upper right abdominal pain radiating to the ipsilateral shoulder tip. She had undergone a laparoscopic cholecystectomy four days earlier without immediate...

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