Differential gene expression changes in the dorsal root versus trigeminal ganglia following peripheral nerve injury in rats

Abstract

Background

The dorsal root (DRG) and trigeminal (TG) ganglia contain cell bodies of sensory neurons of spinal and trigeminal systems, respectively. They are homologs of each other; however, differences in how the two systems respond to injury exist. Trigeminal nerve injuries rarely result in chronic neuropathic pain (NP). To date, no genes involved in the differential response to nerve injury between the two systems have been identified. We examined transcriptional changes involved in the development of trigeminal and spinal NP.

Methods

Trigeminal and spinal mononueropathies were induced by chronic constriction injury to the infraorbital or sciatic nerve. Expression levels of 84 genes in the TG and DRG at 4, 8 and 21 days post‐injury were measured using real‐time PCR.

Results

We found time dependent and ganglion specific transcriptional regulation that may contribute to the development of corresponding neuropathies. Among genes significantly regulated in both ganglia Cnr2, Grm5, Htr1a, Il10, Oprd1, Pdyn, Prok2 and Tacr1 were upregulated in the TG but downregulated in the DRG at 4 days post‐injury; at 21 days post‐injury, Adora1, Cd200, Comt, Maob, Mapk3, P2rx4, Ptger1, Tnf, and Slc6a2 were significantly upregulated in the TG but downregulated in the DRG.

Conclusions

Our findings suggest that spinal and trigeminal neuropathies due to trauma are differentially regulated. Subtle but important differences between the two ganglia may affect NP development.

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Pain thresholds and intensities of CRPS type I and neuropathic pain in respect to sex

Abstract

Background and aims

Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers.

Methods

QST data of 1252 patients (669 female, 583 male) with PNI (n=342), PNP (n=571) or CRPS (n=339), and average pain intensity reports from previously published studies were included. Absolute and z‐values (adjusted for age and body region) of cold, heat, pressure (PPT) and pinprick pain thresholds were compared in generalized linear models with aetiology, duration of underlying pain disease and average pain intensity as fixed effects.

Results

Average pain intensity during the past four weeks did not differ between women and men, in both mean and range. In women absolute pain thresholds for cold, heat and pinprick were lower than in males across all diagnoses (p<.05). However, after z‐transformation these differences disappeared except for PPT in CRPS (p=.001).

Discussion

Pain thresholds in patients show only minor sex differences. However, these differences mimic those observed in healthy subjects and do not seem to be linked to specific pathophysiological processes.

Significance

Female healthy participants and female patients with neuropathic pain conditions or CRPS I report lower pain thresholds compared to males, but pain intensity is similar and there is no sex difference in the extent to which the thresholds are altered in neuropathic pain or CRPS. Thus, the sex differences observed in various chronic pain conditions mimic those obtained in healthy participants, indicating that these differences are not linked to specific pathophysiological processes and are of minor clinical relevance.

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Small Fibre Pathology in Chronic Whiplash‐Associated Disorder: A Cross‐Sectional Study

Abstract

Background

Mechanisms underpinning ongoing symptoms in chronic whiplash associated‐disorder (WAD) are not well understood. People with chronic WAD can exhibit sensory dysfunction consistent with small nerve fibre pathology, including thermal hypoaesthesia and hyperalgesia. This study investigated small fibre structure and function in chronic WAD.

Methods

Twenty‐four people with chronic WAD (median [IQR] age 49 [15] years, 16 females) and 24 pain‐free controls (50 [17] years, 16 females) were recruited. Intraepidermal nerve fibre density (IENFD) and dermal innervation were assessed by skin biopsy. This was performed at i) the lateral index finger on the primary side of pain and ii) superior to the lateral malleolus on the contralateral side. Quantitative sensory testing was performed over the hand.

Results

The WAD group exhibited lower IENFD at the finger (WAD: median [IQR] 4.5 [4.9] fibres/mm; control 7.3 [3.9]; p = 0.010), but not the ankle (WAD: mean [SD] 7.3 [3.7] fibres/mm; control 9.3 [3.8]; p = 0.09). Dermal innervation was lower in the WAD group at the finger (WAD: median [IQR] 3.7 [2.8] nerve bundles/mm²; controls: 4.9 [2.1]; p = 0.017) but not the ankle (WAD: median [IQR] 2.1 [1.9] nerve bundles/mm²; controls: 1.8 [1.8]; p = 0.70). In the WAD group, hand thermal and light touch detection were impaired, and heat pain thresholds were lowered (p ≤ 0.037).

Conclusions

Findings suggest small fibre structural and functional deficits in chronic WAD, implicating potential involvement of small fibre pathology.

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Association between objectively measured physical behaviour and neck‐ And/or low back pain: A systematic review

Abstract

Background and objective

Clinical guidelines recommend physical activity to manage neck pain (NP) and low back pain (LBP). However, studies used to support these guidelines are based on self‐reports of physical behaviour which are prone to bias and misclassification. This systematic review aimed to investigate associations between objectively measured physical behaviour and the risk or prognosis of NP and/or LBP.

Databases and data treatment

Literature searches were performed in MEDLINE, Embase, and Scopus from their inception until January 18th, 2019. We considered prospective cohort studies for eligibility. Article selection, data extraction, and critical appraisal were carried out by independent reviewers. Results were stratified on activity/sedentariness.

Results

Ten articles out of 897 unique records identified met the inclusion criteria, of which eight studied working populations with mainly blue‐collar workers. The overall results indicate that increased sitting time at work reduces the risk of NP and LBP while increased physical activity during work and/or leisure increases the risk of these conditions among blue‐collar workers; however, associations were weak. Physical activity was not associated with prognosis of LBP (no studies investigated prognosis of NP). Most of the included articles have methodological shortcomings.

Conclusions

This review indicates that, among blue‐collar workers, increased sitting at work may protect against NP and LBP, while increased physical activity during work and/or leisure may increase this risk. There was no evidence supporting physical activity as a prognostic factor for LBP. Findings should be interpreted with caution due to the weak associations and few available studies with methodological shortcomings.

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Relationship Between Gliding and Lateral Femoral Pain in Patients With Trochanteric Fracture

Publication date: March 2020

Source: Archives of Physical Medicine and Rehabilitation, Volume 101, Issue 3

Author(s): Kengo Kawanishi, Shintarou Kudo, Katsushi Yokoi

Abstract

Objective

To investigate the association between gliding and lateral femoral pain with trochanteric fracture (TF).

Design

Prospective cohort study.

Setting

The survey was conducted at approximately 3 weeks and 11 weeks post operation.

Participants

Patients (N=23) with TF after surgery.

Interventions

Not applicable.

Main Outcome Measure

Pain was assessed using a numeric rating scale for the following 5 conditions: rest pain, tenderness pain, stretch pain (SP), contraction pain, and weight-loading pain. Based on weight-loading pain, the subjects were divided into 2 groups: severe and moderate. Gliding of both the vastus lateralis (VL) muscle and subcutaneous (SC) tissue were recorded during knee motion using B-mode ultrasonography with a 12-MHz linear transducer fixed on the lateral thigh using an original fixation device. Particle image velocimetry analysis software was adapted to create the flow velocity of both VL muscle and SC tissue from echo imaging, and 2 regions of interest were selected on the VL muscle and SC tissue. Gliding was calculated using a coefficient of correlation from each time series data set.

Results

Gliding and pain (stretch/contraction) were significantly different between the 2 groups at 3 weeks post operation. Changes in both weight-loading pain (r=0.49) and SP (r=0.42) correlated significantly with improvements in gliding.

Conclusion

Patients with weight-loading pain after surgery for TF showed decreased gliding during recovery, and an improvement in gliding was associated with improvements in both weight-loading pain and SP.

Graphical abstract

We examined the association between tissues gliding and lateral femoral pain using a Particle Image Velocimetry assay. An improvement in gliding correlates with an improvement in postoperative pain (Load pain/Stretch pain) with trochanteric fracture. Gliding is an important factor in lateral femoral pain after trochanteric fracture.

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Beneficial Effects of Nonsurgical Treatment for Symptomatic Thumb Carpometacarpal Instability in Clinical Practice: A Cohort Study

Publication date: March 2020

Source: Archives of Physical Medicine and Rehabilitation, Volume 101, Issue 3

Author(s): Robbert M. Wouters, Harm P. Slijper, Lisa Esteban Lopez, Steven E.R. Hovius, Ruud W. Selles, R.A.M. Blomme, B.J.R. Sluijter, D.J.J.C. van der Avoort, A. Kroeze, J. Smit, J. Debeij, E.T. Walbeehm, G.M. van Couwelaar, G.M. Vermeulen, J.P. de Schipper, J.F.M. Temming, J.H. van Uchelen, H.L. de Boer, K.P. de Haas, O.T. Zöphel

Abstract

Objective

To describe outcomes of nonsurgical treatment for symptomatic thumb carpometacarpal joint (CMC-1) instability. Secondary, to evaluate the conversion rate to surgical treatment.

Design

Prospective cohort study.

Setting

A total of 20 outpatient clinics for hand surgery and hand therapy in the Netherlands.

Participants

A consecutive sample of patients with symptomatic CMC-1 instability (N=431).

Intervention

Nonsurgical treatment including exercise therapy and an orthosis.

Main Outcome Measures

Pain (visual analog scale [VAS], 0-100) and hand function (Michigan Hand Outcomes Questionnaire [MHQ], 0-100) at baseline, 6 weeks, and 3 months. Conversion to surgery was recorded for all patients with a median follow-up of 2.8 years (range, 0.8-6.7y).

Results

VAS scores for pain during the last week, at rest, and during physical load improved with a mean difference at 3 months of 17 (97.5% CI, 9-25), 13 (97.5% CI, 9-18), and 19 (97.5% CI, 12-27), respectively (P<.001). No difference was present at 3 months for MHQ total score, but the subscales activities of daily living, work, pain, and satisfaction improved by 7 (97.5% CI, 1-14), 10 (97.5% CI, 4-16), 5 (97.5% CI, 2-9), and 12 (97.5% CI, 2-22) points, respectively (P<.001-.007). After median follow-up of 2.8 years, only 59 participants (14%) were surgically treated. Both in the subgroups that did and did not convert to surgery, VAS pain scores decreased at 3 months compared with baseline (P<.001-.010), whereas MHQ total score did not improve in both subgroups. However, VAS and MHQ scores remained worse for patients who eventually converted to surgery (P<.001).

Conclusions

In this large sample of patients with symptomatic CMC-1 instability, nonsurgical treatment demonstrated clinically relevant improvements in pain and aspects of hand function. Furthermore, after 2.8 years, only 14% of all patients were surgically treated, indicating that nonsurgical treatment is a successful treatment of choice.

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Changes in Trunk and Pelvis Motion Among Persons With Unilateral Lower Limb Loss During the First Year of Ambulation

Publication date: March 2020

Source: Archives of Physical Medicine and Rehabilitation, Volume 101, Issue 3

Author(s): Caitlin E. Mahon, Courtney M. Butowicz, Christopher L. Dearth, Brad D. Hendershot

Abstract

Objective

To retrospectively investigate trunk-pelvis kinematic outcomes among persons with unilateral transtibial and transfemoral limb loss with time from initial independent ambulation with a prosthesis, while secondarily describing self-reported presence and intensity of low back pain. Over time, increasing trunk-pelvis range of motion and decreasing trunk-pelvis coordination with increasing presence and/or intensity of low back pain were hypothesized. Additionally, less trunk-pelvis range of motion and more trunk-pelvis coordination for persons with more distal limb loss was hypothesized.

Design

Inception cohort with up to 5 repeated evaluations, including both biomechanical and subjective outcomes, during a 1-year period (0, 2, 4, 6, 12 months) after initial ambulation with a prosthesis.

Setting

Biomechanics laboratory within military treatment facility.

Participants

Twenty-two men with unilateral transtibial limb loss and 10 men with unilateral transfemoral limb loss (N=32).

Interventions

Not applicable.

Main Outcome Measures

Triplanar trunk-pelvis range of motion and intersegmental coordination (continuous relative phase) obtained at self-selected (∼1.30m/s) and controlled (∼1.20m/s) walking velocities. Self-reported presence and intensity of low back pain.

Results

An interaction effect between time and group existed for sagittal (P=.039) and transverse (P=.009) continuous relative phase at self-selected walking velocity and transverse trunk range of motion (P=.013) and sagittal continuous relative phase (P=.005) at controlled walking velocity. Trunk range of motion generally decreased, and trunk-pelvis coordination generally increased with increasing time after initial ambulation. Sagittal trunk and pelvis range of motion were always less and frontal trunk-pelvis coordination was always greater for persons with more distal limb loss. Low back pain increased for persons with transtibial limb loss and decreased for persons with transfemoral limb loss following the 4-month time point.

Conclusions

Temporal changes (or lack thereof) in features of trunk-pelvis motions within the first year of ambulation help elucidate relationships between (biomechanical) risk factors for low back pain after limb loss.

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Chronic Pain Characteristics and Gait in Older Adults: The MOBILIZE Boston Study II

Publication date: March 2020

Source: Archives of Physical Medicine and Rehabilitation, Volume 101, Issue 3

Author(s): Elisa F. Ogawa, Ling Shi, Jonathan F. Bean, Jeffrey M. Hausdorff, Zhiyong Dong, Brad Manor, Robert R. McLean, Suzanne G. Leveille

Abstract

Objective

To investigate a proposed cognitively-mediated pathway whereby pain contributes to gait impairments by acting as a distractor in community-living older adults.

Design

A cross-sectional study of a population-based cohort of older adults.

Setting

Urban and suburban communities in a large metropolitan area.

Participants

Community-living participants (N=302) 70 years and older recruited from a previous population-based cohort.

Interventions

Not applicable.

Main Outcome Measures

Gait parameters including gait speed, stride length, double support and swing characteristics, and variability were assessed under single- and dual-task conditions involving cognitive challenges (eg, counting backward). A joint pain questionnaire assessed pain distribution in the back and major joints. We examined pain-gait relationships using multivariable linear regression and bootstrapping mediation procedures.

Results

Forty-three percent of participants had pain in 2 or more musculoskeletal sites. Pain distribution was related to slower gait speed and other gait characteristics for all gait conditions. Associations persisted after adjustment for age, sex, education, body mass index, medication, and vision. Decrements in gait measures related to pain were comparable with decrements in gait related to dual-task conditions. There were no differences in dual-task cost among the pain distribution groups. Adjusted for confounders, pain-gait relationships appear mediated by selective attention.

Conclusions

These findings suggest that chronic pain contributes to decrements in gait, including slower gait speed, and that it operates through a cognitively-mediated pathway. Further research is needed to understand the mechanisms via pain alters mobility and to develop interventions to improve mobility among older adults with chronic pain.

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Behavioral Factors and Unintentional Injuries After Spinal Cord Injury

Publication date: March 2020

Source: Archives of Physical Medicine and Rehabilitation, Volume 101, Issue 3

Author(s): Yue Cao, Nicole DiPiro, Chao Li, Jon Roesler, James S. Krause

Abstract

Objective

To identify the relationships of behavioral factors with unintentional injuries among participants with traumatic spinal cord injury (SCI).

Design

Cross-sectional.

Setting

Medical university in the Southeastern United States.

Participants

Participants (N=4670) met the following inclusion criteria: traumatic SCI of at least 1-year duration, minimum of 18 years of age, and residual impairment from SCI (noncomplete recovery). Of these, 2516 were identified from a specialty hospital and 2154 were identified from population-based state surveillance systems.

Interventions

Not applicable.

Main Outcome Measures

Participants completed self-report assessments including multiple behavioral variables, SCI variables, and demographic characteristics. Primary outcome was unintentional injuries during the past 12 months.

Results

Twenty-three percent (n=969) reported at least 1 unintentional injury in the past year serious enough to receive medical care in a clinic, emergency department, or hospital, and the average number of times injured was 1.82 among those with at least 1 injury. Prescription medication use for pain and depression, nonmedical medication use, use of prescription medication for purposes other than prescribed, and binge drinking were associated with a greater odds of unintentional injury. There were some differences between fall-related and non–fall-related unintentional injuries, with ambulation associated with greater odds of fall-related injuries but lower odds of non–fall-related injuries. Participants identified through population-based systems were at greater risk of falls compared with those identified through a traditional specialty hospital.

Conclusions

Unintentional injuries were prevalent among people with SCI. After controlling for injury and demographic characteristics, multiple risk behaviors were related to the odds of unintentional injuries. Intervention studies are needed to address modifiable behaviors that may reduce the risk of injury.

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Profiles of Psychological Adaptation Outcomes at Discharge From Spinal Cord Injury Inpatient Rehabilitation

Publication date: March 2020

Source: Archives of Physical Medicine and Rehabilitation, Volume 101, Issue 3

Author(s): Mayra Galvis Aparicio, Valerie Carrard, Davide Morselli, Marcel W.M. Post, Claudio Peter, Xavier Jordan, Bertrand Léger, Michael Baumberger, Hans Peter Gmünder, Armin Curt, Martin Schubert, Margret Hund-Georgiadis, Kerstin Hug, Thomas Troger, Daniel Joggi, Hardy Landolt, Nadja Münzel, Mirjam Brach, Gerold Stucki, Christine Fekete

Abstract

Objective

To evaluate the effect of a newly acquired spinal cord injury (SCI) by identifying profiles of psychological adaptation outcomes at discharge from inpatient rehabilitation, using several outcome measures in parallel and to examine biopsychosocial factors associated with profile membership.

Design

Cross-sectional analysis of data from the Swiss Spinal Cord Injury inception cohort study.

Setting

Inpatient rehabilitation.

Participants

Individuals 16 years old or older with recently diagnosed SCI who finished clinical rehabilitation in 1 of the 4 major national rehabilitation centers (N=370).

Interventions

Not applicable.

Main Outcome Measures

Life satisfaction, general distress, and symptoms of depression and anxiety were assessed using a single item from the International SCI Quality of Life Basic Data Set, the Distress Thermometer, and the Hospital Anxiety and Depression Scale respectively.

Results

Using latent profile analysis, 4 profiles of psychological adaptation outcomes were identified displaying different levels of impact, ranging from Minimal to Severe. Regarding covariates associated with profile membership, higher optimism, purpose in life, and self-efficacy indicated a higher probability of having a Minimal impact profile. Additionally, males, individuals with better functional independence, and those with an absence of pain were more likely to show a Minimal impact profile.

Conclusions

Among the participants, 70% showed Minimal or Low impact profiles. Our findings support that individuals can show positive responses across several outcome measures even at an early time after the injury onset (eg, at discharge from inpatient rehabilitation). Moreover, our results indicate that beyond functional independence, improvement, and pain management, a rehabilitation process that strengthens psychological resources might contribute to better adaptation outcomes.

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[Clinical Picture] Immunosuppressed gardener pricked by roses grows Legionella longbeachae

A 78-year-old gardener presented to our hospital with a fever and a painful swollen right hand. She had started to feel pain in both her ring and little finger 4 days earlier, which spread to her wrist. She also said she had been feverish but did not report having rigors. Notably, she said she frequently handled manure and had puncture wounds from repeatedly pricking herself on the thorns on her rosebushes. She had a history of temporal arteritis and was being treated with prednisolone 40 mg daily.

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Neuromodulation: more than a placebo effect?

No abstract available

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Selective modulation of tonic aversive qualities of neuropathic pain by morphine in the central nucleus of the amygdala requires endogenous opioid signaling in the anterior cingulate cortex

The amygdala is a key subcortical region believed to contribute to emotional components of pain. As opioid receptors are found in both the central (CeA) and basolateral (BLA) nuclei of the amygdala, we investigated the effects of morphine microinjection on evoked pain responses, pain-motivated behaviors, dopamine release in the nucleus accumbens (NAc), and descending modulation in rats with left-side spinal nerve ligation (SNL). Morphine administered into the right or left CeA had no effect on nerve injury–induced tactile allodynia or mechanical hyperalgesia. Right, but not left, CeA morphine produced conditioned place preference (CPP) and increased extracellular dopamine in the NAc selectively in SNL rats, suggesting relief of aversive qualities of ongoing pain. In SNL rats, CPP and NAc dopamine release following right CeA morphine was abolished by blocking mu opioid receptor signaling in the rostral anterior cingulate cortex (rACC). Right CeA morphine also significantly restored SNL-induced loss of the diffuse noxious inhibitory controls, a spino-bulbo-spinal pain modulatory mechanism, termed conditioned pain modulation in humans. Microinjection of morphine into the BLA had no effects on evoked behaviors and did not produce CPP in nerve-injured rats. These findings demonstrate that the amygdalar action of morphine is specific to the right CeA contralateral to the side of injury and results in enhancement of net descending inhibition. In addition, engagement of mu opioid receptors in the right CeA modulates affective qualities of ongoing pain through endogenous opioid neurotransmission within the rACC, revealing opioid-dependent functional connections from the CeA to the rACC.

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The new micropatterned interdigitated electrode for selective assessment of the nociceptive system

Abstract

Background

In this neurophysiological study, we aimed at verifying the nociceptive selectivity of the new, micropatterned electrode (150IDE), recently designed to generate an electric field limited to the intraepidermal free nerve endings.

Methods

Using the new 150IDE we recorded evoked potentials after stimulation of the face and hand dorsum in 22 healthy participants and in patients with exemplary conditions selectively affecting the nociceptive system. We also measured the peripheral conduction velocity at the upper arm and verified the nociceptive selectivity of 150IDE assessing the effect of a selective block of nociceptive nerve fibres of radial nerve with local anaesthetic infiltration. In healthy participants and in patients we have also compared the 150IDE‐evoked potentials with laser‐evoked potentials.

Results

In healthy participants, the 150IDE evoked pinprick sensation and reproducible scalp potentials, with latency similar to laser‐evoked potentials. The mean peripheral conduction velocity, estimated at the upper arm, was 12 m/s. The selective nociceptive fibre block of the radial nerve abolished the scalp potentials elicited by the 150IDE stimulation. In patients, the 150IDE‐evoked potentials reliably detected the selective damage of the nociceptive system.

Conclusions

Our neurophysiological study shows that this new 150IDE provides selective information on nociceptive system.

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Lumbar Axial Rotation Kinematics in an Upright Sitting and With Forward Bending Positions in Men With Nonspecific Chronic Low Back Pain

Study Design. A controlled cross-sectional study. Objective. The aim of this study was to compare the kinematics of lumbar axial rotation while sitting in an upright and forward bending position in men suffering with and without nonspecific chronic low back pain (NSCLBP). Summary of Background Data. Lumbar rotation while sitting is an important factor in the mechanism of low back pain. Nevertheless, its kinematics has scarcely been investigated. Methods. Range of motion (ROM in), average velocity (AV), maximum velocity (MV), and maximal acceleration (MA) of lumbar rotation while sitting in an upright (UP-sitting) and full forward bending position (FFB-sitting) were examined using an industrial lumbar motion monitor in 50 men (25 with NSCLBP and 25 controls). Pain level and the Rolland Morris questionnaire (RMQ) were also included. Results. All examined kinematical parameters were significantly lower in men with NSCLBP compared with the controls (↓ROM = 16%–29%; ↓AV = 35%–53%; ↓MV = 3%–46%; ↓MA = 7%–44%) and significantly decreased when moving from UP-sitting to FFB-sitting. In the UP-sitting, the ROM and AV in both groups and the right rotation-MV in the NSCLBP group were always greater during the right rotation compared to the left (NSCLBP = ROM: Δ3.92°, AV: Δ2.74°/s, MV:Δ3.61°/s; controls = ROM: Δ3.46°, AV: Δ1.72°/s). The left rotation-MV was significantly greater compared to the right only in FFB-sitting in the controls (Δ3.03°/s). In all kinematical parameters in the NSCLBP group, no correlations were found in the visual analogue scale (VAS) levels (4.43 ± 1.47) or RMQ total score (12.32 ± 5.44). Conclusion. The kinematic parameters of lumbar rotation were reduced in men with NSCLBP compared with controls both in an UP-sitting and FFB-sitting. In both groups, NSCLBP and controls, asymmetry in lumbar rotation kinematics was indicated as well as a decrease when moving from UP-sitting to FFB-sitting. Level of Evidence: 3

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Association Between Excessive Weight Gain During Pregnancy and Persistent Low Back and Pelvic Pain After Delivery

Study Design. Retrospective study. Objective. To investigate the association between gestational weight gain (GWG) during pregnancy and persistent low back and pelvic pain (LBPP) after delivery. Summary of Background Data. Persistent LBPP after delivery is a risk factor for developing depression and chronic pain as well as incurring sick leave. Women experience weight gain during pregnancy. Excessive weight gain places a greater burden on the musculoskeletal system. However, little is known about how GWG is associated with LBPP after delivery. Methods. After Ethics Committee approval, we analyzed 330 women at 4 months after delivery who had LBPP during pregnancy. The exclusion criteria were as follows: specific low back pain, multiple birth, and incomplete data. Four months after delivery, LBPP was assessed using a self-report questionnaire. Persistent LBPP was defined as pain at 4 months after delivery with an onset during pregnancy or within 3 weeks after delivery. GWG was calculated as the difference between the pregnancy weight and the prepregnancy weight, which we categorized into three groups: <10, 10 to <15, and ≥15 kg. Other confounding factors including age, height, weight at 4 months after delivery, parity, gestational week, mode of delivery, weight of the fetus, and prepregnancy LBPP were assessed. We used logistic regression analysis to calculate LBPP odds ratios (ORs) according to GWG. Results. The prevalence of persistent LBPP was 34.1% (n = 113). Compared with women with a GWG of <10 kg, women with a GWG of ≥15 kg had a higher prevalence of persistent LBPP (OR = 2.77, 95% confidence interval (95% CI) = 1.28–5.96, adjusted OR = 2.35, 95% CI = 1.06–5.21); however, no significant difference was found for women with a GWG of 10 to <15 kg (OR = 1.18, 95% CI = 0.72–1.92, adjusted OR = 1.02, 95% CI = 0.61–1.72). Conclusions. Our study showed that excessive weight gain during pregnancy is one of the risk factors of persistent LBPP. Appropriate weight control during pregnancy could help prevent persistent LBPP after delivery. Level of Evidence: 3

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Profile of Patients With Acute Low Back Pain Who Sought Emergency Departments: A Cross-sectional Study

Study Design. A cross-sectional study. Objective. The aim of this study is to describe the profile of patients with acute low back pain (LBP) who sought emergency departments (EDs) in Brazilian public hospitals. We also described the profile of these patients according to the STarT Back Screening Tool (SBST). Summary of Background Data. LBP is the most common musculoskeletal condition worldwide and is one of the main complaints in EDs. There is a lack of evidence describing the profile of these patients from low- to middle-income countries. Methods. This is a cross-sectional study involving patients with a new episode of nonspecific acute LBP that was conducted between August 2014 and August 2016. Variables related to clinical, psychological, sociodemographic and work status characteristics were investigated through structured, in-person oral questionnaire. Results. A total of 600 patients were included in the study. The majority of the patients were women (58%), with a median of eight points on pain intensity (measured on an 11-point scale) and 17 points on disability (measured on a 24-item questionnaire). With regards to the SBST evaluation, 295 (49.2%) patients were classified as being at high risk of developing an unfavorable prognosis with a median pain intensity of nine points on pain intensity, 20 points on disability, and seven points on depression (measured on an 11-point scale). Despite this, the majority of the patients (74%) continued working normally without interference from LBP. Conclusion. Identifying the profile of patients seeking care in EDs can help to define effective management for LBP in low- and middle-income countries. Patients with nonspecific acute LBP who seek EDs in Brazil present high levels of pain intensity and disability. Most patients were classified as having a high risk of developing an unfavorable prognosis. Level of Evidence: 2

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Oxytocin modulates intrinsic neural activity in patients with chronic low back pain

Abstract

Background

Modulation of pain perception by oxytocin (OXT) has attracted increased scientific and clinical interest. Neural mechanisms underlying these effects are poorly understood. In this study, we aimed to investigate the effects of intranasally applied OXT on intrinsic neural activity in patients with chronic low back pain (cLBP).

Methods

Twenty‐four male patients with cLBP and 23 healthy males were examined using resting‐state functional magnetic resonance imaging. Participants were scanned twice and received either intranasally applied OXT (24 international units) or placebo 40 minutes before scanning. The fractional amplitude of low‐frequency fluctuations (fALFF) was computed to investigate regionally specific effects of OXT on intrinsic neural activity. In addition a multivariate statistical data analysis strategy was employed to explore OXT‐effects on functional network strength.

Results

Differential effects of OXT were observed in cLBP and healthy controls. FALFF decreased in left nucleus accumbens and right thalamus in cLBP and increased in right thalamus in healthy controls after OXT application compared to placebo. OXT also induced activity changes in bilateral thalamus, left caudate nucleus, and right amygdala in cLBP. OXT was associated with increased medial frontal, parietal and occipital functional network strength, though this effect was not group‐specific. Regression analyses revealed significant associations between left nucleus accumbens, left caudate nucleus, and right amygdala with pain‐specific psychometric scores in cLBP.

Conclusions

These data suggest OXT‐related modulation of regional activity and neural network strength in patients with cLBP and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by OXT.

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A randomised, double‐blind, crossover, dose ranging study to determine the optimal dose of oral opioid to treat breakthrough pain for patients with advanced cancer already established on regular opioids

Abstract

Pain in people with advanced cancer is prevalent. When a stable dose of opioids is established, people still experience episodic breakthrough pain for which dosing of an immediate release opioid is usually a proportion of the total daily dose.

This multi‐site, double blind, randomised trial tested three dose proportions (1/6, 1/8, 1/12 of total daily dose) in two blocks, each block with three dose proportions in random order (6 numbered bottles in total). When participants required opioid breakthrough doses and it was their first breakthrough dose for that study day, they took the next numbered bottle rather than their usual breakthrough dose. (Subsequent doses on that day reverted to their usual dose.)

Eighty five people were randomised in this study of whom 81 took at least one dose and 73 (90%) took at least block one (one of each dose proportion). No dose was found to be optimal at 30 min with approximately one third of participants showing maximal reduction with each dose proportion. Median time to pain relief was 120 min. There were no differences in harms: drowsiness, confusion, nausea or vomiting at 30, 60 or 120 min.

This adequately powered study did not show any difference with three dose proportions for reduction in pain intensity, time to pain relief, pain control on the subsequent day nor any difference in harms. From first principles, this suggests 1/12 the 24 hourly dose should be used as the lowest dose that delivers benefit. Future studies should include a placebo arm.

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Pain interventions in adults with intellectual disability: a scoping review and pharmacological considerations

Abstract

Background and Objective

Having to deal on a daily routine with prescriptions in adults with intellectual disability (ID), we systematically reviewed the literature on the specificities of pain interventions in that population, focusing on medication and trying to gather practical information on appropriate pain treatments. Given the scarcity of the literature on the topic, we also discussed the pharmacological considerations to be taken into account when prescribing analgesic drugs in that vulnerable population.

Databases and Data Treatment

Articles on pain and intellectual disability were searched in the Medline and Google scholar electronic databases using the key words "Intellectual Disability", "Developmental Disability" and specific keywords for pharmacological and non‐pharmacological pain interventions. Preset outcomes about pharmacological treatment specificity, efficacy and safety were then collected.

Results

One hundred and fifty‐two articles were found and 16 were retained based on our inclusion and exclusion criteria. Of the 16 articles, 5 were topical reviews. Amongthe 11 remaining articles, 5 discussed pharmacological interventions, 4 considered non‐pharmacological interventions and 2 discussed both. As anticipated, the literature matching our specific outcomes about the pharmacological treatment of pain was scarce and and for the most part not designed to answer the questions of specificity, efficacy and safety of pain treatment in adults with ID.

Conclusion

The specificity of analgesic treatments in adults with ID is a totally unexplored domain. In the absence of clinical guidelines, pharmacological facts ‐ such as inter‐individual variability in drug response, pharmacokinetic and pharmacodynamic interactions, frequent comorbidities and ease of administration ‐ must be systematically integrated, when prescribing in the population of adults with ID.

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Operant conditioning as a new mechanism of placebo effects

Abstract

Background and Objective

Placebo effects are considered to be learning phenomena. There is a growing body of evidence supporting the role of both classical conditioning and observational learning in the induction of placebo effects. However, the third basic learning process, operant conditioning, was not considered as a mechanism of placebo effects until very recently. Unlike classically conditioned responses, which are induced by stimuli that precede the behavior, operant behaviors are shaped and maintained by their consequences. Thus, placebo effects may not only result from pairing an active intervention with the stimuli that accompany its administration (placebo), but also positive (e.g., the ability to perform a desired activity) or negative reinforcement (e.g., pain relief) of placebo administration may increase the frequency of taking placebos in the future. The paper reviews the evidence supporting the idea of operant conditioning as a mechanism of placebo effects and discusses it in the context of the general principles of operant conditioning, the operant conditioning account of pain modulation, and research findings on the role of operant conditioning in pain modulation.

Databases and Data Treatment

This is a narrative review.

Results

Seven lines of research are proposed to study the role of operant conditioning in producing placebo effects.

Conclusions

Operant conditioning account of placebo effects has practical implications both for routine clinical practice and the placebo arms of randomized controlled trials.

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[Perspectives] Two men, two losses, two eras

Losing any loved one is painful. Part, taught the Buddha, of the inescapable fate of us all. But losing a spouse, a life partner, is different—these are the people with whom we are most intimate, who we've chosen, who have chosen us to share the joys and burdens of life's journey. And, if we are blessed with mutual long lives, to share the wisdom, the pleasures and pains of ageing together. Medicine has known since antiquity that the loss of a spouse can have profound consequences for the surviving member of a couple.

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The epidemiology of cerebral palsy in adulthood: A systematic review and meta-analysis of the most frequently studied outcomes

Publication date: Available online 12 February 2020

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Marloes van Gorp, Sander R. Hilberink, Suzie Noten, Joyce L. Benner, Henk J. Stam, Wilma MA. van der Slot, Marij E. Roebroeck

Abstract

Objective

To describe the epidemiology of health status, impairments, activities and participation in adults with cerebral palsy (CP).

Data sources

Embase, Medline, Web-of-Science, PsycINFO, CINAHL, Cochrane and Google Scholar were searched for three themes (‘cerebral palsy’, ‘adult’, and ‘outcome assessment’) in literature published between January 2000 and December 2018.

Study selection

Full paper, peer-reviewed, English journal articles on descriptive, observational or experimental studies describing the most studied outcomes in adults with CP (n ≥ 25, age ≥ 18 years) were included. Studies were included in the analyses if frequently studied outcomes were described in at least 3 studies using similar methods of assessment.

Data extraction

Data were extracted independently by two authors from 65 articles (total n=28429) using a standardized score sheet.

Data synthesis

Meta analyses revealed that overall, on average 65.1% (95% CI: 55.1;74.5) of adults with CP experienced pain, 57.9% (51.1;64.6) were ambulant, 65.5% (61.2;69.7) had little or no limitation in manual ability, 18.2% (10.6;27.2) had tertiary education, 39.2% (31.5;47.1) were employed and 29.3% (9.0;55.3) lived independently. Considering adults without intellectual disability, proportions of individuals who were ambulant (72.6% [58.8;84.5]) and lived independently (90.0% [83.8;94.9]) were higher (respectively p=0.014 and p<0.01). The Fatigue Severity Scale score was 4.1 (3.8;4.4). Epilepsy (28.8% [20.1;38.4]) and asthma (28.3% [18.7;38.9]) were especially prevalent comorbidities.

Conclusions

The present systematic review and meta-analysis on the epidemiology of adults with CP provided state-of-the-art knowledge on the most frequently studied outcomes. On the average adults with CP are fatigued, a majority experiences pain, is ambulant and has little or no difficulty with manual ability. On average, 40% is employed and 30% lives independently. More uniformity in assessment and reports is advised to improve knowledge on epidemiology and gain insight in more outcomes.

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Between placebo and nocebo: Response to control treatment is mediated by amygdala activity and connectivity

Abstract

Background

In experimental placebo and nocebo studies, neutral control treatments are often administered for comparison with active treatments, but are of little interest, as, on average, they result in little change. Yet, when considered at an individual level, they fluctuate between baseline and subsequent measurements and may reveal important information about participants' placebo/nocebo responding tendencies.

Methods

In a paradigm involving application of creams paired with positive, negative and neutral expectations, some subjects rated identical stimuli in the neutral condition as more painful while others as less painful after treatment with inert cream. We divided subjects into two groups based on the median split in these pre‐post responses in the neutral control condition, and investigated (a) fMRI signal differences (post minus pre) between the two groups in neutral condition, and (b) seed‐based resting state connectivity of the bilateral amygdala, known to be involved in emotional self‐regulation, as well as ambiguous stimulus processing and aversive learning.

Results

The results suggested that subjects who rated the same pain stimuli after treatment with explicitly neutral cream as more painful showed stronger fMRI activation of the amygdala during the experiment and had higher connectivity between the left amygdala and the striatum at rest. Neutral pre‐post changes predicted behavioural placebo/nocebo response in this and two independent datasets.

Conclusion

These findings suggest that measuring pre‐post change in the neutral control condition might provide important information about subjects' individual differences in placebo/nocebo response.

Significance

Pre‐post changes in pain ratings in neutral conditions are modulated by amygdala activity and connectivity and can be used to predict placebo/nocebo responses.

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Issue Information

European Journal of Pain, Volume 24, Issue 3, Page 473-474, March 2020.

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Analgesic efficacy of 10% lidocaine spray during nasoenteral catheterization: Randomized triple‐blind trial

Abstract

Background

Pain is a common experience during nasoenteral catheterization. Although the procedure causes discomfort and distress to patients, procedural pain remains neglected and undertreated.

Objective

To evaluate the analgesic efficacy of the use of 10% lidocaine spray during nasoenteral catheterization.

Method

A randomized, triple‐blind trial of 50 patients was performed. The patients were randomly assigned to two groups: an intervention group (IG), in which 10% lidocaine spray combined with 2% lidocaine gel was used, and a control group (CG), in which a saline solution spray combined with 2% lidocaine gel was used. Pain and discomfort were assessed during and after nasoenteral catheterization using numerical rating scale (NRS) and the visual analogue scale (VAS), respectively.

Results

Intervention group participants reported lower pain scores during (0.20 ± 0.71 vs. 5.00 ± 2.84, p < .001; |d| = −0.677) and after (0.00 ± 0.00 vs. 2.80 ± 2.83, p < .001; |d| = −0.718) nasoenteral catheterization compared to the CG.

Conclusion

Spraying 10% lidocaine spray before nasoenteral catheterization was most effective for relieving discomfort and pain, with lower pain and discomfort recorded in NRS and VAS. Topical administration of 10% lidocaine spray is therefore a suggested measure for procedural pain relief related to nasoenteral catheterization.

Significance

The use of 10% lidocaine spray was more effective in relieving procedural pain and discomfort during nasoenteral catheterization. Patients who received 10% lidocaine spray registered lower discomfort and pain scores than those from 2% lidocaine gel group; there were less complications among patients in the IG.

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Enhanced pain modulation capacity among individuals with borderline personality disorder: A possible mechanism underlying their hypoalgesia

Abstract

Background

Ample evidence suggests that individuals with borderline personality disorder (BPD) exhibit hyposensitivity to pain. Since the underlying mechanism of the pain hyposensitivity is unknown, we tested here for the first time whether this hyposensitivity is pain specific or exists also for innocuous sensation, and whether it is associated with enhanced descending pain modulation capabilities.

Methods

Participants were 55 women; 22 patients with BPD and 33 matched healthy controls. Testing included the measurement of warmth sensation threshold (WST), heat‐pain threshold (HPT), pain adaptation, conditioned pain modulation (CPM) and temporal summation of heat‐pain (TSP). The level of dissociation was also evaluated.

Results

Women with BPD had higher WST and HPT compared with healthy controls. Moreover, women with BPD had greater magnitude of pain adaptation and CPM as well as higher dissociation level compared to controls. In neither the BPD nor the control group did WST and HPT correlate with pain adaptation, CPM or dissociation. In the BPD group only, HPT inversely correlated with the magnitude of TSP.

Conclusions

Women with BPD present generalized hyposensitivity to both innocuous and noxious stimuli. Furthermore, women with BPD exhibit more efficient pain inhibition capabilities than healthy controls. While efficient pain modulation may underlie pain hyposensitivity in BPD, both traits may exist independently from each other, or may be moderated by another factor such as dissociation.

Significance

On the basis of testing pronociceptive and antinociceptive components among individuals with BPD and healthy controls, this study reveals enhanced ability to inhibit pain among woman with borderline personality disorder (BPD) which may underlie hyposensitivity to both noxious and innocuous stimuli and perhaps also self‐injurious behaviour among these individuals. The study contributes novel information on possible mechanisms involved in BPD manifestations.

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The effects of long‐term opioid treatment on the immune system in chronic non‐cancer pain patients: A systematic review

Abstract

Background and objective

Opioids have been increasingly prescribed for chronic non‐cancer pain (CNCP). An association between long‐term opioid treatment (L‐TOT) of CNCP patients and suppression of both the innate and the adaptive immune system has been proposed. This systematic review aims at investigating the effects of L‐TOT on the immune system in CNCP patients.

Databases and data treatment

A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL for relevant articles was performed. Studies examining measures of both the innate and the adaptive immune system in adult CNCP patients in L‐TOT (≥4 weeks of intake) were included. Outcomes and the level of evidence were analysed.

Results

A total of 382 studies were identified; however, 376 were excluded (352 inappropriate methodology, 21 duplicates, three full‐text could not be obtained) and one randomized controlled trial (RCT) and five cross‐sectional studies were included and analysed. L‐TOT compared with no treatment was associated with a lower percentage of natural killer (NK) cells, a lower absolute number of CD56^bright NK cells, a higher absolute number of IL‐2‐activated NK cells and a higher concentration of IL‐1β as a response to toll‐like receptor (TLR) agonists stimulation (Pam3CSK4, LPS, Imiquimod). No other significant differences were reported. Generalizability of the results was limited due to inconsistency of outcomes and an overall low quality of the studies.

Conclusions

L‐TOT may alter the immune system in CNCP patients, but the level of evidence is still weak. More studies are needed to clarify the impact of L‐TOT on immune system function.

Significance

This systematic review found indication that long‐term opioid treatment alters the immune system in chronic non‐cancer pain patients. These alterations involved the NK cells and IL‐1β production. However, the level of evidence is weak.

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Perioperative intravenous low‐dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo‐controlled study

Abstract

Background

Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low‐dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, 6 and 12 months after major lower back surgery.

Methods

In this single‐centre randomized trial, 80 patients received intravenous ketamine 0.25 mg/kg preoperatively, followed by 0.25 mg kg⁻¹ hr⁻¹ intraoperatively, and 0.1 mg kg⁻¹ hr⁻¹ from 1 hr before the end of surgery until the end of recovery room stay; 80 controls received placebo.

Results

Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8 mg (IQR 67.4–106.7) and the median plasma level was 97 ng/ml (IQR 77.9–128.0). At 6 months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI −10.7 to 21.1; p = .607). At 12 months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI −6.7 to 23.6; p = .319).

Conclusions

In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low‐dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at 6 or 12 months postoperatively.

Significance

We were unable to show any analgesic benefit of a short‐term perioperative ketamine infusion as an adjuvant to multimodal analgesia in patients with a high prevalence of neuropathic lower back pain undergoing major back surgery. Based on these data, the widespread opinion that ketamine is universally analgesic across different pain conditions must be challenged.

Prior presentations

Abstract presentation at the annual congress of the Swiss Society of Anaesthesiology, 2016, Basel, Switzerland.

Clinical trial number and registry URL

Registered by Dr Christoph Czarnetzki as principal investigator on February 20, 2008 at clinicaltrials.gov (NCT00618423).

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Effects of fitness level and exercise intensity on pain and mood responses

Abstract

Background

The phenomenon of exercise‐induced hypoalgesia and concomitant mood changes is well‐established. How exercise‐induced hypoalgesia and affective responses are shaped by the intensity of an acute exercise bout and individual fitness levels is as yet not well‐understood. This study investigates whether heat pain threshold (PTh), pain tolerance (PTol) and affective parameters are modulated by the intensity of an acute exercise bout and/or individuals’ fitness level. Stronger analgesic responses are hypothesized after high‐intensity exercise in physically fitter subjects, possibly in sync with concomitant mood changes.

Methods

Thirty‐three healthy men were recruited (sedentary: N = 17 or recreational: N = 14; mean age: 25.3 ± 4.4 years). After a fitness assessment on a cycle ergometer, subjects underwent three experimental conditions on separate days: high (20 min exercise 20% above lactate threshold), low (20 min exercise 20% below lactate threshold) and control (seated rest). Before and after each intervention Positive and Negative Affect Schedule, PTh and PTol (cold water emersion test) were assessed.

Results

Results indicate an increase of the Positive Affect Scale (high: 26.7 ± 9.0 vs. 32.9 ± 7.1, p < .001; low: 26.3 ± 7.2 vs. 32.0 ± 7.0, p < .001) and PTh (high: 45.1 ± 3.1°C vs. 46.0 ± 2.6°C, p = .003; low: 45.4 ± 2.7°C vs. 45.9 ± 2.6°C, p = .012) after both exercise conditions. In an exploratory analysis, PTol significantly increased only after the high exercise condition (51.2 ± 33.7 s vs. 72.4 ± 64.0 s, p = .045). Fitness level was positively correlated with the increase in PTol from pre to post high‐intensity exercise (r = .59, p (one‐tailed) = .002).

Conclusion

Exercise‐induced hypoalgesia depends on exercise intensity and appears to be influenced by individual fitness status, independent of mood responses.

Significance

Antinociceptive effects can be elicited by physical exercise and have been extensively investigated in the literature. However, the relation between exercise intensity, fitness status, and the degree of antinociception is not well‐understood. This randomized intervention provides novel evidence that antinociceptive effects indeed depend on exercise intensity, but also on general fitness status. Data extend the existing literature by highlighting aspects of exercise behaviour that promote antinociception. Effects do not simply mirror positive affective responses induced by exercise, hence, indicating partially distinct underlying mechanisms.

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Is there evidence of efficacy of nonpharmacological interventions in the acute pain management during the laser retinal photocoagulation of patients with diabetic retinopathy?

European Journal of Pain, Volume 24, Issue 3, Page 665-666, March 2020.

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Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial

In this paper by Bråten and colleagues (BMJ 2019;367:l5654, doi:10.1136/bmj.l5654, published 16 October 2019), an error was spotted in table S6 of the supplementary appendix, describing post hoc...

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Gabapentinoids: when hope is restored, it’s obvious that increasing analgesics will bring no benefit

Ian Hamilton need not be so downcast about alternatives for reducing gabapentinoid use.1Kairos Rehabilitation, a registered charity, is a pain management clinic led by a GP with specialist interest,...

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Novel approach towards musculoskeletal phenotypes

Abstract

Background

The multidimensional array of clinical features and prognostic factors makes it difficult to optimize management within the heterogeneity of patients with common musculoskeletal pain. This study aimed to identify phenotypes across prognostic factors and musculoskeletal complaints. Concurrent and external validity were assessed against an established instrument and a new sample, respectively, and treatment outcome was described.

Methods

We conducted a longitudinal observational study of 435 patients (aged 18‐67 years) seeking treatment for non‐specific complaints in the neck, shoulder, low back or multisite/complex pain in primary health care physiotherapy in Norway. Latent class analysis was used to identify phenotypes based on eleven common prognostic factors within four biopsychosocial domains; pain, beliefs and thoughts, psychological, and activity and lifestyle.

Results

Five distinct phenotypes were identified. Phenotype 1 (n=77, 17.7%) and 2 (n=142, 32.6%) were characterized by the lowest scores across all biopsychosocial domains. Phenotype 2 showed somewhat higher levels of symptoms across the biopsychosocial domains. Phenotype 3 (n=89, 20.5%) and 4 (n=78, 17.9 %) were more affected across all domains, but phenotype 3 and 4 had opposite patterns in the psychological and pain domains. Phenotype 5 (n=49, 11.3 %) were characterized by worse symptoms across all domains, indicating a complex phenotype. The identified phenotypes had good external and concurrent validity, also differentiating for the phenotypes in function and health‐related quality of life outcome at 3 months follow‐up.

Conclusion

The phenotypes may inform the development of targeted interventions aimed at improving the treatment efficiency in patients with common musculoskeletal disorders.

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Viscero‐visceral hyperalgesia in dysmenorrhea plus previous urinary calculosis: role of myofascial trigger points and their injection treatment in the referred area

Abstract

Background

Women with dysmenorrhea plus symptomatic urinary calculosis experience enhanced pain and referred muscle hyperalgesia from both conditions than women with one condition only (viscero‐visceral hyperalgesia). The study aimed at verifying if enhanced dysmenorrhea persists after urinary stone elimination in comorbid women and if local anesthetic inactivation of myofascial trigger points (TrPs) in the lumbar area (of urinary pain referral) also relieves dysmenorrhea.

Methods

31 women with dysmenorrhea plus previous urinary calculosis (Dys+PrCal) and lumbar TrPs, and 33 women with dysmenorrhea without calculosis (Dys) underwent a 1‐year assessment of menstrual pain and muscle hyperalgesia in the uterus referred area (electrical pain threshold measurement in rectus abdominis, compared with thresholds of 33 healthy controls). At the end of the year, 16 comorbid patients underwent inactivation of TrPs through anesthetic injections, while the remaining 12 received no TrP treatment. Both groups were monitored for another year at the end of which thresholds were re‐measured.

Results

In year1, Dys+PrCal presented significantly more painful menstrual cycles and lower abdominal thresholds than Dys, thresholds of both groups being significantly lower than normal (p<0.001). Anesthetic treatment vs no treatment of the lumbar TrP significantly reduced the number of painful cycles during year2 and significantly increased the abdominal thresholds (p<0.0001).

Conclusion

Viscero‐visceral hyperalgesia between uterus and urinary tract may persist after stone elimination due to nociceptive inputs from TrPs in the referred urinary area, since TrPs treatment effectively reverses the enhanced menstrual symptoms. The procedure could represent an integral part of the management protocol in these conditions.

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Effectiveness of motor imagery and action observation training on musculoskeletal pain intensity: A systematic review and meta‐analysis

Abstract

Background and objective

Movement representation techniques such as motor imagery (MI) and action observation (AO) could play an important role in the field of rehabilitation of patients with musculoskeletal pain; however, the effects of these tools on clinical pain remain unclear. Our objective is therefore to develop a systematic review and meta‐analysis of the effects of MI and AO regarding pain intensity on patients with musculoskeletal pain.

Databases and data treatment

MEDLINE, EMBASE, CINAHL and Google Scholar were searched. Last search was run on July 2019. Meta‐analysis was conducted to determine the effectiveness on pain intensity in patients with post‐surgical pain or chronic pain, and GRADE was used to rate the quality, certainty, and applicability of the evidence.

Results

A total of 10 studies were included. AO or MI were compared versus usual rehabilitation care. The meta‐analysis showed statistically significant differences in MI and AO interventions in patients with pain after surgery in 6 studies, with a large clinical effect (n=124; SMD=−0.84; 95% CI 1.47 to −0.21). In patients with chronic pain, results showed statistically significant differences in MI and AO interventions in 3 studies, with a large clinical effect (n=83; SMD=−2.14; 95% CI −3.81 to −0.47). Risk of bias, imprecision and inconsistency decreased the GRADE level of evidence.

Conclusions

There was very low‐quality evidence regarding the effects of movement representation techniques intervention (AO and MI) on pain intensity in patients with post‐surgical pain. In addition, there was very low‐quality evidence regarding effects of MI and AO interventions on chronic pain.

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Effectiveness of motor imagery and action observation training on musculoskeletal pain intensity: A systematic review and meta‐analysis

Abstract

Background and objective

Movement representation techniques such as motor imagery (MI) and action observation (AO) could play an important role in the field of rehabilitation of patients with musculoskeletal pain; however, the effects of these tools on clinical pain remain unclear. Our objective is therefore to develop a systematic review and meta‐analysis of the effects of MI and AO regarding pain intensity on patients with musculoskeletal pain.

Databases and data treatment

MEDLINE, EMBASE, CINAHL and Google Scholar were searched. Last search was run on July 2019. Meta‐analysis was conducted to determine the effectiveness on pain intensity in patients with post‐surgical pain or chronic pain, and GRADE was used to rate the quality, certainty, and applicability of the evidence.

Results

A total of 10 studies were included. AO or MI were compared versus usual rehabilitation care. The meta‐analysis showed statistically significant differences in MI and AO interventions in patients with pain after surgery in 6 studies, with a large clinical effect (n=124; SMD=−0.84; 95% CI 1.47 to −0.21). In patients with chronic pain, results showed statistically significant differences in MI and AO interventions in 3 studies, with a large clinical effect (n=83; SMD=−2.14; 95% CI −3.81 to −0.47). Risk of bias, imprecision and inconsistency decreased the GRADE level of evidence.

Conclusions

There was very low‐quality evidence regarding the effects of movement representation techniques intervention (AO and MI) on pain intensity in patients with post‐surgical pain. In addition, there was very low‐quality evidence regarding effects of MI and AO interventions on chronic pain.

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[Comment] Stoma closure reinforcement with biological mesh and incisional hernia

Incisional hernia is a prevalent complication after abdominal surgery, with an incidence as high as 39% at 2 years.1 Incisional hernia adversely affects health-related quality of life, particularly in regards to pain, physical function, ability to work, and feelings about appearance.2 The condition can lead to serious complications due to bowel obstruction with incarceration or strangulation3 and can recur after surgical repair, necessitating additional procedures.4 Incisional hernia represents a true global public health issue with a substantial burden to health-care systems around the world.

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[Obituary] Ronald Hyman Melzack

Co-inventor of the gate theory of pain. He was born in Montreal, QC, Canada, on July 19, 1929, and died there on Dec 22, 2019, aged 90 years.

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AAPT Diagnostic Criteria for Chronic Low Back Pain

Chronic low back pain conditions are highly prevalent and constitute the leading cause of disability worldwide. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the US Food and Drug Administration and the American Pain Society (APS), have combined to create the ACTTION-APS Pain Taxonomy (AAPT). The AAPT initiative convened a working group to develop diagnostic criteria for chronic low back pain. The working group identified three distinct low back pain conditions which result in a vast public health burden across the lifespan.

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Physical rehabilitation needs per condition type: Results from the Global Burden of Disease study 2017

Publication date: Available online 5 February 2020

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Tiago S. Jesus, Michel D. Landry, Dina Brooks, Helen Hoenig

Abstract

Objective

To determine how total physical rehabilitation needs have been distributed per relevant condition groups (musculoskeletal & pain, neurological cardiothoracic, neoplasms, pediatric, and HIV-related), globally and across countries of varying income level.

Design

Sub-group, secondary analyses of data from the Global Burden of Disease 2017. Data for the year 2017 are used for determining current needs, and data from every year between 1990 and 2017 for determining changing trends.

Settings

Globally and High, Upper Middle, Lower Middle, and Low-Income countries. Participants: Not applicable

Interventions

Not applicable.

Main Outcome Measure

Years Lived with Disability per 100,000 people (YLD Rates) for the 6 condition groups.

Results

In 2017, musculoskeletal & pain conditions accounted for 52.6% of the total physical rehabilitation needs worldwide; HIV-related for 5.7% of the physical rehabilitation needs in low-income nations, but about 1% in all other locations. Worldwide, significant increases in YLD Rates were observed since 1990 for the 6 condition groups (p<0.01). However, across country types, we observed significant decreases in YLD Rates for specific conditions: pediatric in high-income countries, and neurological and neoplasm conditions in low-income (p<0.01). In upper middle-income countries, YLD Rates from neurological and neoplasm conditions grew exponentially since 1990, with overall increases of 67% and 130%, respectively.

Conclusion

At a global scale, physical rehabilitation needs per-capita are growing for all major condition groups, with musculoskeletal & pain conditions currently accounting for over half of those needs. Countries of varying income level have different typologies and evolutionary trends in their rehabilitation needs.

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A woman with nail changes

A 64 year old woman presented with two weeks of redness, pain, swelling, and exudation of the periungual skin around all fingernails and toenails. Examination found she had complete destruction over...

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Early Self-directed Home Exercise Program After Anterior Cervical Discectomy and Fusion: A Pilot Study

Study Design. Pilot randomized controlled trial. Objective. To examine the acceptability and preliminary safety and outcome effects of an early self-directed home exercise program (HEP) performed within the first 6 weeks after anterior cervical discectomy and fusion (ACDF). Summary of Background Data. Little is known regarding optimal postoperative management after ACDF. Methods. Thirty patients (mean ± standard deviation, age = 50.6 ± 11.0 years, 16 women) undergoing ACDF were randomized to receive an early HEP (n = 15) or usual care (n = 15). The early HEP was a 6-week self-directed program with weekly supportive telephone calls to reduce pain and improve activity. Treatment acceptability was assessed after the intervention period (6 weeks after surgery). Safety (adverse events, radiographic fusion, revision surgery) was determined at routine postoperative visits. Disability (Neck Disability Index), pain intensity (Numeric Rating Scale for neck and arm pain), physical and mental health (SF-12), and opioid use were assessed preoperatively, and at 6 weeks and 6 and 12 months after surgery by an evaluator blinded to group assignment. Results. Participants reported high levels of acceptability and no serious adverse events with the early HEP. No difference in fusion rate was observed between groups (P > 0.05) and no participants underwent revision surgery. The early self-directed HEP group reported lower 6-week neck pain than the usual care group (F = 3.3, P = 0.04, r2 = 0.3, mean difference = −1.7 [−3.4; −0.05]) and lower proportion of individuals (13% vs. 47%) using opioids at 12 months (P = 0.05). No other between-group outcome differences were observed (P > 0.05). Conclusion. An early self-directed HEP program was acceptable to patients and has the potential to be safely administered to patients immediately after ACDF. Benefits were noted for short-term neck pain and long-term opioid utilization. However, larger trials are needed to confirm safety with standardized and long-term radiograph assessment and treatment efficacy. Level of Evidence: 2

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Increased Fibrogenic Gene Expression in Multifidus Muscles of Patients With Chronic Versus Acute Lumbar Spine Pathology

Study Design. Prospective observational study-basic science (Level 1). Objective. The aim of this study was to compare expression of functional groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways between paraspinal muscle biopsies from individuals with acute and chronic lumbar spine pathology. Summary of Background Data. Low back pain is a complex and multifactorial condition that affects a majority of the general population annually. Changes in muscle tissue composition (i.e., fatty and fibrotic infiltration) are a common feature in individuals with lumbar spine pathology associated with low back pain, which often results in functional loss. Understanding the molecular underpinnings of these degenerative changes in different phases of disease progression may improve disease prevention and treatment specificity. Methods. Intraoperative biopsies of the multifidus muscle were obtained from individuals undergoing surgery for acute (<6-month duration) or chronic (>6-month duration) lumbar spine pathology. Expression of 42 genes related to myogenesis, atrophy, adipogenesis, metabolism, inflammation, and fibrosis were measured in 33 samples (eight acute, 25 chronic) using qPCR, and tissue composition of fat, muscle, and fibrosis was quantified using histology. Results. We found that tissue composition of the biopsies was heterogeneous, resulting in a trend toward lower RNA yields in biopsies with higher proportions of fat (r <�−0.39, P <� 0.1). There were no significant differences in gene expression patterns for atrophy (P > 0.635), adipogenesis (P > 0.317), myogenesis (P > 0.320), or inflammatory (P > 0.413) genes after adjusting for the proportion of muscle, fat, and connective tissue. However, in the fibrogenesis pathway, we found significant upregulation of CTGF (P = 0.046), and trends for upregulation of COL1A1 (P = 0.061), and downregulation of MMP1 and MMP9 (P = 0.061) in the chronic group. Conclusion. There is increased fibrogenic gene expression in individuals with chronic disease when compared to acute disease, without significant differences in atrophic, myogenic, adipogenic, or inflammatory pathways, suggesting increased efforts should be made to prevent or reverse fibrogenesis to improve patient function in this population. Level of Evidence: N/A

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Validation of PROMIS CATs and PROMIS Global Health in an Interdisciplinary Pain Program for Patients With Chronic Low Back Pain

Study Design. Retrospective cohort study. Objective. To (1) confirm validity of Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and pain interference computer-adaptive tests (CATs) and (2) assess the validity of PROMIS Global Health (GH) and five additional PROMIS CATs: social role satisfaction, fatigue, anxiety, depression, and sleep disturbance in a population of patients with chronic low back pain (cLBP) who completed a 3-month Interdisciplinary Pain Program (IPP). Summary of Background Data. Recent recommendations for assessing outcomes in patients with cLBP have included PROMIS scales; however, there is a need for further evaluation, and PROMIS GH has not been studied in this population. Methods. The study cohort included patients with cLBP who completed the entirety of a 3-month IPP between August 2016 and December 2018. Patient-reported outcome measures (PROMs) were analyzed before the start of the IPP and at graduation. Convergent and discriminant validity were evaluated using Pearson correlation coefficients. Known groups’ validity assessed the change in PROMIS scores stratified by improvement on the Modified LBP Disability Questionnaire. Responsiveness was evaluated with standardized response means based on global impression of change. Results. IPP was completed by 217 patients (67.7% women, age 53.8 ± 12.8). Convergent validity was supported (P <� 0.01 for all pairwise PROMs comparisons). All PROMs improved significantly by graduation, with the largest improvement for PROMIS pain interference, physical function, social role satisfaction, and Modified LBP Disability Questionnaire. Known groups’ validity demonstrated the greatest change on PROMIS physical function, social role satisfaction, pain interference, and depression. Responsiveness was supported for all PROMs in 170 (78.3%) patients who indicated at least minimal improvement (standardized response means 0.43–1.06). Conclusion. Our study provides support of PROMIS CATs, highlights the importance of including other meaningful outcome measures, such as social role satisfaction, and provides the first validation of PROMIS GH, in patients with cLBP. PROMs collection can be streamlined through the use of PROMIS CATs which offer advantages over legacy measures. Level of Evidence: 3

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The Influence of Preoperative Mental Health on PROMIS Physical Function Outcomes Following Minimally Invasive Transforaminal Lumbar Interbody Fusion

Study Design. Retrospective. Objective. To demonstrate whether preoperative mental health status can be predictive of postoperative functional outcomes as measured by Patient-Reported Outcome Measurement Information System Physical Function (PROMIS PF) following minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). Summary of Background Data. There is a paucity of scientific investigations into the association between preoperative mental health as evaluated by a validated questionnaire such as the Short Form-12 Mental Health Composite Score (SF-12 MCS) and postoperative outcomes following MIS TLIF. Methods. Patients undergoing a primary MIS TLIF were retrospectively reviewed and stratified into cohorts based on preoperative SF-12 MCS scores. The Physical Function scores of PROMIS, of which there are other domains including Pain Interference, Sexual Function, and Cognitive Function, were compared between the cohorts. In addition, the improvement in PROMIS scores based on preoperative SF-12 MCS scores following MIS TLIF was analyzed using multivariate linear regression. Results. One hundred seventy-two patients were included: 85 patients (49.4%) had a preoperative SF-12 MCS score <50 and 87 (50.6%) had a preoperative SF-12 MCS score ≥50. Patients with poorer mental health demonstrated significantly worse PROMIS PF scores preoperatively (33.8 vs. 36.5, P <� 0.001), as well as at all postoperative timepoints: 6-weeks (35.1 vs. 38.4, P <� 0.001), 3-months (38.9 vs. 42.9, P <� 0.001), 6-months (41.4 vs. 45.5, P <� 0.001), and 1-year (42.4 vs. 47.6, P <� 0.001). However, at the 1-year timepoint, patients with worse mental health reported experiencing significantly less improvement from baseline (postoperative change of 8.6 vs. 11.1, P = 0.002). Conclusion. Patients with worse preoperative mental health not only demonstrated worse preoperative PROMIS PF scores, but also continued to have significantly worse postoperative outcomes. However, the postoperative improvement experienced by patients was similar in the short-term following surgery regardless of preoperative mental health status. Patients with poor mental health experienced significantly less postoperative improvement only at the 1-year timepoint. Level of Evidence: 3

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Total physical activity and risk of chronic low back and knee pain in middle‐aged and elderly Japanese people: the Murakami Cohort Study

Abstract

Background

Specific components of physical activity, such as vigorous exercise and heavy occupational work, are known to increase the risk of chronic low back pain (CLBP) and knee pain (CKP), but impacts of other components are less known. This study aimed to assess the relationship between total physical activity and risk of CLBP and CKP from a public health perspective.

Methods

Participants were 7,565 individuals, aged 40–74 years, who did not have CLBP or CKP, and who participated in the 5‐year follow‐up survey. A self‐administered questionnaire was used to obtain information on demographics, body size, and lifestyle (including physical activity) in the baseline survey in 2011‐2013, and on CLBP and CKP using Short Form 36 (SF‐36) in the follow‐up survey. Sitting, standing, walking, and strenuous work for occupational activity were assessed for total physical activity, and walking slowly, walking quickly, light to moderate exercise, and strenuous exercise were assessed for leisure‐time physical activity using metabolic equivalent hours/day (METs score).

Results

Mean age of participants was 60.1 years (SD, 8.8). Participants with higher METs scores had a significantly higher risk of CKP (P for trend=0.0089, OR of 4th quartile=1.29, 95%CI: 1.04‐1.59 vs. 1st quartile), but not CLBP. An intermediate leisure‐time METs score was associated with a lower risk of CLBP (OR=0.75, 95%CI: 0.61‐0.92 vs. 0 METs‐group).

Conclusions

A high level of total physical activity may increase the risk of CKP, whereas an intermediate level of leisure‐time physical activity may decrease the risk of CLBP, in middle‐aged and elderly individuals.

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Step aside CRISPR, RNA editing is taking off

Nature, Published online: 04 February 2020; doi:10.1038/d41586-020-00272-5

Making changes to the molecular messengers that create proteins might offer flexible therapies for cancer, pain or high cholesterol, in addition to genetic disorders.

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