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Excitability of the motor cortex can be suppressed during muscle pain. Yet the mechanisms are largely unknown. Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were examined as possible candidate mechanisms to underpin this change. SICI and ICF were investigated in 11 healthy individuals before, during and after infusion of hypertonic saline into right first dorsal interosseous (FDI). Using paired-pulse transcranial magnetic stimulation (TMS), interstimulus intervals of 2, 3, and 13 ms were investigated. Pain intensity and quality were recorded using a 10-cm visual analogue scale and the McGill Pain Questionnaire. Resting motor threshold and motor-evoked potentials (MEPs) to single TMS stimuli were recorded before and after pain. Electromyographic recordings were made from right FDI and abductor digiti minimi. Participants reported an average pain intensity of 5.8 (1.6) cm. MEP amplitudes decreased in both muscles. Compared with the pre-pain condition, SICI was increased following pain, but not during. ICF was decreased both during and after pain when compared with the pre-pain condition. These findings suggest that muscle pain differentially modulates SICI and ICF. Although the functional relevance is unknown, we hypothesize decreased facilitation and increased inhibition may contribute to the restriction of movement of a painful body part. PERSPECTIVE: This article provides evidence for decreased intracortical facilitation and increased short interval intracortical inhibition in response to muscle pain. This finding is relevant to clinicians as a mechanism which may underlie restricted movement in acute and chronic pain. [ABSTRACT FROM AUTHOR]

Pain hypersensitivity is present in some people with acute low back pain (LBP) and thought to be involved in the development of chronic LBP. Early evidence suggests that pain hypersensitivity in acute LBP precedes poor long-term outcome. We aimed to examine whether the presence of pain hypersensitivity in acute LBP influenced recovery status at 6 months and differentiated how pain and disability changed over time. Participants with acute nonspecific LBP (<6 weeks after pain onset, N = 118) were included in this longitudinal study. Quantitative sensory testing, including pressure and heat pain thresholds, and conditioned pain modulation and questionnaires were compared at baseline and longitudinally (at 3 and 6 months) between recovered and unrecovered participants. Using k-means clustering, we identified subgroups based on baseline sensory measures alone, and in combination with psychological factors, and compared pain and disability outcomes between subgroups. Sensory measures did not differ at baseline or longitudinally between recovered (N = 50) and unrecovered (N = 68) participants. Subgrouping based on baseline sensory measures alone did not differentiate pain or disability outcomes at any timepoint. Participants with high psychological distress at baseline (N = 19) had greater disability, but not pain, at all timepoints than those with low psychological distress, regardless of the degrees of pain sensitivity. Our findings suggest that pain hypersensitivity in acute LBP does not precede poor recovery at 6 months or differentiate how pain and disability change over time. High psychological distress during acute LBP is associated with unremitting and pronounced disability, while pain severity is unaffected. PERSPECTIVE: Pain hypersensitivity is thought to be involved in the transition to chronic LBP. Contradictory to prevailing hypothesis, our findings suggest pain hypersensitivity alone in acute LBP does not precede poor recovery. High psychological distress in acute LBP has a stronger influence than pain hypersensitivity on long-term disability, but not pain outcomes., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

The molecular processes driving the transition from acute to chronic low back pain (LBP) remain poorly understood and are likely to be sexually dimorphic. This study aimed to explore sex differences in the serum proteomic profile of people experiencing an acute LBP episode and determine if serum protein concentrations were associated with three-month outcome. Serum samples were collected through venepuncture from 30 female and 29 male participants experiencing an acute LBP episode. Serum samples underwent trypsin digestion and fractionation using hydrophobic interaction chromatography and were then analysed using mass-spectrometry. Mass-spectrometry spectra were searched in the Swissprot database for protein identification. Sex differences in protein abundance changes were evident upon inspection of fold changes. Multivariable data analysis identified 21 serum proteins during the acute episode that correctly classified 93% of males and 23 serum proteins that correctly classified 90% of females with ongoing LBP at 3 months. Pathway analysis suggested the differentially expressed proteins during acute LBP were frequently involved in immune, inflammatory, complement, or coagulation responses. This data provides preliminary evidence that biological processes during an acute LBP episode may contribute to the resolution, or persistence, of LBP symptoms at 3 months, however, these processes differ between males and females. PERSPECTIVE: Differential expression of serum proteins was observed between male and female participants during an acute LBP episode. This preliminary work provides a foundation for future research targeting distinct immune system processes in males and females that may interfere with the transition from acute to chronic LBP., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Lateral epicondylalgia (LE), commonly referred to as tennis elbow, is a musculoskeletal condition characterized by pain and sensorimotor dysfunction. In some individuals with chronic unilateral LE, sensorimotor symptoms develop on the unaffected side despite no evidence of tissue damage. Altered interhemispheric inhibition (IHI) is one mechanism that could underpin this phenomenon. The aim of this cross-sectional study was to examine IHI between the primary motor cortices (M1) in individuals with chronic LE and healthy controls. In 20 individuals with chronic LE and 20 healthy participants, transcranial magnetic stimulation was used to assess 1) short and long-latency IHI from the affected (corresponding to the injured side) to the unaffected M1 and 2) corticomotor excitability of the affected and unaffected M1. Sensorimotor function was evaluated bilaterally at the extensor carpi radialis brevis muscle using pressure pain threshold, grip strength, 2-point discrimination, and temporal summation tests. Short- and long-latency IHI from the affected to the unaffected M1 and corticomotor excitability of the affected and unaffected M1 were not altered in individuals with LE compared with healthy participants. No differences in sensorimotor function were observed for the affected or unaffected extensor carpi radialis brevis muscles when individuals with LE were compared with healthy participants. IHI is not altered in individuals with chronic LE. Further studies are required to determine the mechanisms that underpin the development of bilateral sensorimotor symptoms in unilateral LE. PERSPECTIVE: IHI is unaltered from the affected M1 (corresponding to the painful muscle) to unaffected M1 in individuals with LE compared to healthy controls. The absence of bilateral sensorimotor dysfunction and low pain severity in this cohort of individuals with LE may explain this finding., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Pain alters motor function. This is supported by studies showing reduced corticomotor excitability in response to experimental pain lasting &lt;90 minutes. Whether similar reductions in corticomotor excitability are present with pain of longer durations or whether alterations in corticomotor excitability are associated with pain severity is unknown. Here we evaluated the evidence for altered corticomotor excitability in response to experimental pain of differing durations in healthy individuals. Databases were systematically searched for eligible studies. Measures of corticomotor excitability and pain were extracted. Meta-analyses were performed to examine: (1) group-level effect of pain on corticomotor excitability, and (2) individual-level associations between corticomotor excitability and pain severity. 49 studies were included. Corticomotor excitability was reduced when pain lasted milliseconds-seconds (hedges g's = -1.26 to -1.55) and minutes-hours (g's = -0.55 to -0.9). When pain lasted minutes-hours, a greater reduction in corticomotor excitability was associated with lower pain severity (g = -0.24). For pain lasting days-weeks, there were no group level effects (g = -0.18 to 0.27). However, a greater reduction in corticomotor excitability was associated with higher pain severity (g = 0.229). In otherwise healthy individuals, suppression of corticomotor excitability may be a beneficial short-term strategy with long-term consequences. PERSPECTIVE: This systematic review synthesised the evidence for altered corticomotor excitability in response to experimentally induced pain. Reduced corticomotor excitability was associated with lower acute pain severity but higher sustained pain severity, suggesting suppression of corticomotor excitability may be a beneficial short-term adaptation with long-term consequences., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Bilateral deficits in sensorimotor function have been observed in unilateral musculoskeletal pain conditions. Altered interhemispheric inhibition (IHI) between primary sensory cortices (S1s) is one mechanism that could explain this phenomenon. However, IHI between S1s in response to acute muscle pain, and the relationship between IHI and pressure pain sensitivity in the unaffected limb have not been examined. In 21 healthy individuals, IHI was assessed using somatosensory evoked potentials in response to paired median nerve electrical stimulation at: 1) baseline; 2) immediately following pain resolution; and 3) at 30-minutes follow-up. Acute muscle pain was induced by injection of hypertonic saline into the right abductor pollicis brevis (APB) muscle. Pressure pain thresholds were assessed at the right and left APB muscles before and 30-minutes after pain resolution. Compared to baseline, IHI from the affected to unaffected S1 was unaltered in response to acute muscle pain immediately following pain resolution, or at 30-minutes follow-up. Pressure pain thresholds were reduced over the right (P = .001) and left (P = .001) APB muscles at 30-minutes follow-up. These findings suggest IHI between S1s is unaffected by acute, short-lasting muscle pain, despite the development of increased sensitivity to pressure in the unaffected APB muscle. PERSPECTIVE: IHI from the affected S1 (contralateral to the side of pain) to unaffected S1 is unaltered following the resolution of acute muscle pain. This finding suggests that IHI between S1s may not be relevant in the development of bilateral sensorimotor symptoms in unilateral pain conditions., (Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Determining the mechanistic causes of complex biopsychosocial health conditions such as low back pain (LBP) is challenging, and research is scarce. Cross-sectional studies demonstrate altered excitability and organization of the somatosensory and motor cortex in people with acute and chronic LBP, however, no study has explored these mechanisms longitudinally or attempted to draw causal inferences. Using sensory evoked potential area measurements and transcranial magnetic stimulation derived map volume we analyzed somatosensory and motor cortex excitability in 120 adults experiencing acute LBP. Following multivariable regression modelling with adjustment for confounding, we identified lower primary (OR = 2.08, 95% CI = 1.22-3.57) and secondary (OR = 2.56, 95% CI = 1.37-4.76) somatosensory cortex excitability significantly increased the odds of developing chronic pain at 6-month follow-up. Corticomotor excitability in the acute stage of LBP was associated with higher pain intensity at 6-month follow-up (B = -0.15, 95% CI: -0.28 to -0.02) but this association did not remain after confounder adjustment. These data provide evidence that low somatosensory cortex excitability in the acute stage of LBP is a cause of chronic pain. PERSPECTIVE: This prospective longitudinal cohort study design identified low sensorimotor cortex excitability during the acute stage of LBP in people who developed chronic pain. Interventions that target this proposed mechanism may be relevant to the prevention of chronic pain., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Aberrant motor cortex plasticity is hypothesized to contribute to chronic musculoskeletal pain, but evidence is limited. Critically, studies have not considered individual differences in motor plasticity or how this relates to pain susceptibility. Here we examined the relationship between corticomotor excitability and an individual's susceptibility to pain as pain developed, was sustained and resolved over 21 days. Nerve growth factor was injected into the right extensor carpi radialis brevis muscle of 20 healthy individuals on day 0, 2, and 4. Corticomotor excitability, pressure pain thresholds and performance on a cognitive conflict task were examined longitudinally (day 0, 2, 4, 6, and 14). Pain and disability were assessed on each alternate day (1,3…21). Two patterns of motor plasticity were observed in response to pain--corticomotor depression or corticomotor facilitation (P = .009). Individuals who displayed corticomotor depression experienced greater pain (P = .027), and had worse cognitive task performance (P = .038), than those who displayed facilitation. Pressure pain thresholds were reduced to a similar magnitude in both groups. Corticomotor depression in the early stage of pain could indicate a higher susceptibility to pain. Further work is required to determine whether corticomotor depression is a marker of pain susceptibility in musculoskeletal conditions. PERSPECTIVE: This article explores individual differences in motor plasticity in the transition to sustained pain. Individuals who developed corticomotor depression experienced higher pain and worse cognitive task performance than those who developed corticomotor facilitation. Corticomotor depression in the early stage of pain could indicate a higher susceptibility to pain., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

The etiologic role of work-related psychological stress in the development of musculoskeletal pain disorders (MDs) has been systematically investigated. Less clear, however, is the role of perceived stress and life stressors. This review aimed to assess the evidence for an etiologic role of perceived stress and life stressors in the development of chronic MDs. Database searches were conducted to identify prospective longitudinal studies that assessed perceived stress and life stressors in individuals without, or in the first 6 weeks of, musculoskeletal pain. The primary outcome was the development of a chronic MD. Methodologic quality was investigated using an adapted version of the Quality Assessment Tool for Observational Cohort studies and Cross-Sectional studies, and the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Seven studies were included representing data from 6 independent cohorts. There was some evidence to support the etiologic role of perceived stress and life stressors in the development of arthritis (low quality) and chronic spinal pain (low quality). The limited number of studies, the poor quality of the evidence, and the heterogeneity of stress measures used across studies suggest that further high quality prospective studies are required to clarify the role of perceived stress and life stressors in the development of chronic MDs. PROSPERO: CRD42017059949 PERSPECTIVE: This review summarizes and critically appraises the evidence for the etiologic role of perceived stress and life stressors in the development of chronic MDs. The limited number of studies, the low quality of the evidence, and the heterogeneity across studies suggest that further research is needed on perceived stress and life stressors in MDs., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Bilateral deficits in sensorimotor function have been observed in unilateral musculoskeletal pain conditions. Evidence suggests a reduction in interhemispheric inhibition (IHI) from the "affected" (contralateral to the side of pain) to the "unaffected" primary motor cortex (M1) could contribute. However, the effect of short-lasting acute muscle pain on IHI, and whether any changes are related to early sensorimotor changes in the unaffected limb, is unknown. Using a cross-sectional study design, IHI was investigated in 20 healthy individuals before, immediately after, and 30 minutes after the induction of acute muscle pain in the right first dorsal interosseous muscle via a bolus injection of hypertonic saline. Transcranial magnetic stimulation was used to assess corticomotor excitability and short and long latency IHI. Pain intensity and quality were recorded using an 11-point numerical rating scale and the McGill Pain Questionnaire. Pressure pain thresholds were assessed in the affected and unaffected first dorsal interosseous and both tibialis anterior muscles. Participants reported an average pain intensity of 4.8 points (standard deviation = 1.3 points). Compared with baseline, corticomotor excitability was decreased at all time points in the affected but not the unaffected M1. IHI was decreased at all time points from the affected to the unaffected M1. Pressure pain thresholds were decreased over both first dorsal interosseous muscles at 30 minutes of follow-up. These findings suggest a decrease in IHI from the affected to the unaffected M1 that occurs rapidly after the onset of acute pain and could contribute to the development of bilateral symptoms. PERSPECTIVE: The affected M1 (contralateral to the side of pain) releases inhibition over the unaffected M1 within minutes after the onset of acute muscle pain. This finding could have relevance for the development of bilateral sensorimotor symptoms in unilateral pain conditions., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Sensorimotor cortical activity is altered in both the immediate acute and chronic stages of musculoskeletal pain. However, these changes are opposite, with decreased cortical activity reported in experimentally induced acute pain (lasting minutes to hours), and increased cortical activity in chronic, clinical pain (lasting >6 months). It is unknown whether sensorimotor cortical activity is altered in acute, clinical musculoskeletal pain (lasting <4 weeks). In 36 individuals with acute, nonspecific, clinical low back pain (LBP) and 36 age- and sex-matched, pain-free controls, we investigated the processing of non-noxious afferent inputs using sensory evoked potentials (SEPs), as well as corticomotor excitability and organization of the primary motor cortex using transcranial magnetic stimulation. Processing of non-noxious sensory inputs was lower (smaller area of the N 80 -N 150 -P 260 SEP complex) in acute LBP (F 1,70  = 45.28, P < .01). The examination of specific SEP components revealed a smaller area of the N 150 and P 260 SEP components in acute LBP, although interindividual variability was high. Motor cortical map volume was lower in acute LBP (F 1,70  = 5.61, P = .02). These findings demonstrate that acute LBP is characterized by lower sensorimotor cortical activity at the group level. However, individual variation was high, suggesting individual adaptation of cortical plasticity in acute pain. PERSPECTIVE: This is the first study to examine sensorimotor cortical activity in the acute stage of clinical LBP. This information is critical for understanding the neurophysiology of acute LBP., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Chronic pain can be associated with movement abnormalities. The primary motor cortex (M1) has an essential role in the formulation and execution of movement. A number of changes in M1 function have been reported in studies of people with chronic pain. This review systematically evaluated the evidence for altered M1 structure, organization, and function in people with chronic pain of neuropathic and non-neuropathic origin. Database searches were conducted and a modified STrengthening the Reporting of OBservational studies in Epidemiology checklist was used to assess the methodological quality of included studies. Meta-analyses, including preplanned subgroup analyses on the basis of condition were performed where possible. Sixty-seven studies (2,290 participants) using various neurophysiological measures were included. There is conflicting evidence of altered M1 structure, organization, and function for neuropathic and non-neuropathic pain conditions. Meta-analyses provided evidence of increased M1 long-interval intracortical inhibition in chronic pain populations. For most measures, the evidence of M1 changes in chronic pain populations is inconclusive., Perspective: This review synthesizes the evidence of altered M1 structure, organization, and function in chronic pain populations. For most measures, M1 changes are inconsistent between studies and more research with larger samples and rigorous methodology is required to elucidate M1 changes in chronic pain populations., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)