The journal of pain : official journal of the American Pain Society
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Over 120 million Americans report experiencing pain in the past 3 months. Among these individuals, 50 million report chronic pain and 17 million report pain that limits daily life or work activities on most days (ie, high-impact chronic pain). Musculoskeletal pain conditions in particular are a major contributor to global disability, health care costs, and poor quality of life. ⋯ PERSPECTIVE: Movement-evoked pain (MEP) is a distinct component of the musculoskeletal pain experience and emerging research area. This article introduces the "Pain-Movement Interface" as a theoretical framework of MEP, highlighting the interface between MEP, pain interference, and activity engagement. Evaluating and treating MEP could improve rehabilitation approaches and enhance patient outcomes.
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Prescription opioid tapering has increased significantly over the last decade. Evidence suggests that tapering too quickly or without appropriate support may unintentionally harm patients. The aim of this analysis was to understand patients' experiences with opioid tapering, including support received or not received for pain control or mental health. ⋯ Patient-centered approaches to tapering include reaching out to monitor how patients are doing, involving patients in decision-making, supporting mental health changes, and allowing for flexibility in the tapering pace. PERSPECTIVE: Patients tapering prescription opioids desire more provider-initiated communication including checking in about pain, setting expectations for withdrawal and mental health-related changes, and providing support for mental health. Patients preferred opportunities to share decisions about taper speed and to have flexibility with pausing the taper as needed.
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Bodily disruptions have been consistently demonstrated in individuals with chronic low back pain. The performance on the left-right judgment task has been purposed as an indirect measure of the cortical proprioceptive representation of the body. It has been suggested to be dependent on implicit motor imagery, although the available evidence is conflicting. ⋯ The absence of differences in the reaction times for the left-right judgment task between both groups, along with inconsistencies in self-reported and quantitative sensory testing data, could question the involvement of implicit motor imagery in solving the task. In conclusion, our results suggest disrupted attentional processing in participants with chronic low back pain to solve the left-right judgment task. PERSPECTIVE: Although there are no differences in the performance of the left-right judgment task (hits, reaction times) between chronic low back pain patients and controls, the analysis of event-related potentials revealed that patients require a higher cognitive load, measured by N1 peak amplitude.
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Deactivation of the medial prefrontal cortex (mPFC) has been broadly reported in both neuropathic pain models and human chronic pain patients. Several cellular mechanisms may contribute to the inhibition of mPFC activity, including enhanced GABAergic inhibition. The functional effect of GABAA(γ-aminobutyric acid type A)-receptor activation depends on the concentration of intracellular chloride in the postsynaptic neuron, which is mainly regulated by the activity of Na-K-2Cl cotransporter isoform 1 (NKCC1) and K-Cl cotransporter isoform 2 (KCC2), 2 potassium-chloride cotransporters that import and extrude chloride, respectively. ⋯ PERSPECTIVE: Chronic pain is associated with the presence of depolarizing GABAA current in the spinal cord, suggesting that pharmacological NKCC1 antagonism has analgesic effects. However, our results show that in neuropathic pain, GABAA current is actually hyperinhibitory in the mPFC, where it contributes to the mPFC functional deactivation. This suggests caution in the use of NKCC1 antagonism to treat pain.
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Meta Analysis
Characterisation of common genetic variants in P2RX7 and their contribution to chronic pain conditions.
The adenosine triphosphate (ATP)-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some have been implicated in chronic pain. In this study, we first systematically characterized all 17 common nonsynonymous variants using whole-cell patch clamp electrophysiology. ⋯ Cumulative allele count analysis did not provide additional insights. In conclusion, our results go beyond reproducing association for rs7958311 with chronic pain and suggest that its unique combination of gain-of-function in channel and loss-of-function in pore activity may explain why it is likely the only common P2RX7 variant with contribution to chronic pain. PERSPECTIVE: This study characterizes all common P2RX7 variants using cellular assays and statistical association analyses with chronic pain, with Markov state modeling of the most robustly associated variant.