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Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain.

ABSTRACT: Neuropathic pain (NeP) remains a significant clinical challenge owing to insufficient awareness of its pathological mechanisms. We elucidated the aberrant metabolism of the cerebral cortex in NeP induced by the chronic constriction injury (CCI) using metabolomics and proteomics analyses. After CCI surgery, the values of MWT and TWL markedly reduced and maintained at a low level. CCI induced the significant dysregulation of 57 metabolites and 31 proteins in the cerebral cortex. Integrative analyses showed that the differentially expressed metabolites and proteins were primarily involved in alanine, aspartate and glutamate metabolism, GABAergic synapse, and retrograde endocannabinoid signaling. Targeted metabolomics and western blot analysis confirmed the alterations of some key metabolites and proteins in endogenous pain-modulatory system. In conclusion, our study revealed the alterations of endocannabinoids system and purinergic system in the CCI group, and provided a novel perspective on the roles of endogenous pain-modulatory system in the pathological mechanisms of NeP.

SUBMITTER: Chen P

PROVIDER: S-EPMC10165265 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain.

Chen Peng P Wang Chen C Gong Qian Q Chai Yihui Y Chen Yunzhi Y Song Cuiwen C Wu Yuanhua Y Wang Long L

iScience 20230413 5

Neuropathic pain (NeP) remains a significant clinical challenge owing to insufficient awareness of its pathological mechanisms. We elucidated the aberrant metabolism of the cerebral cortex in NeP induced by the chronic constriction injury (CCI) using metabolomics and proteomics analyses. After CCI surgery, the values of MWT and TWL markedly reduced and maintained at a low level. CCI induced the significant dysregulation of 57 metabolites and 31 proteins in the cerebral cortex. Integrative analys ...[more]

PMID: 37168579

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Project description:BackgroundExercise-induced hypoalgesia (EIH) is characterized by a reduction in pain perception and sensitivity across both exercising and non-exercising body parts during and after a single bout of exercise. EIH is mediated through central and peripheral mechanisms; however, the specific effect of muscle contraction alone on EIH remains unclear. Moreover, previous studies on electrical muscle stimulation (EMS) have primarily focused on local analgesic effects, often relying on subjective pain reports. This study investigated the contribution of EMS-induced muscle contractions to systemic analgesia, independent of motor cortex activity. We aimed to explore the underlying mechanisms of EIH by analyzing the influence of skeletal muscle mass (SMM), skeletal muscle mass index (SMI), and conditioned pain modulation (CPM).MethodsIn this crossover study, 27 healthy young adults participated in EMS and sham interventions, separated by a washout period of 2 to 3 days. SMM, SMI, and CPM were measured before the first intervention. Pressure pain thresholds (PPT) were evaluated before and after each intervention. EMS was applied to the non-dominant quadriceps at a frequency of 30 Hz, a pulse duration of 300 μs, and a duty cycle of 5 s on and 10 s off, without inducing joint movement, for 20 min. The sham intervention used the same settings, but the stimulation amplitude was insufficient to induce muscle contraction in the quadriceps. The average current intensity was 16.0 ± 3.2 mA and 11.3 ± 2.3 mA in the EMS and sham condition, respectively.ResultsIn the EMS condition, PPT significantly increased in the stimulated quadriceps but not in non-contracted sites. There were strong positive correlations between changes in PPT and both SMM and SMI, but not CPM. The sham condition showed no significant effects at any assessment sites.ConclusionsThese findings suggest that the analgesic effects of EMS-induced muscle contractions are primarily localized to the stimulated muscle tissues, rather than mediated by the central pain modulatory mechanisms.Trial registrationThis study was enrolled in the UMIN-CTR Clinical Trial Registry (registration number: UMIN000051951; date of approval: August 19, 2023).

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Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain.

Publications

Alterations of endogenous pain-modulatory system of the cerebral cortex in the neuropathic pain.

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