• ZhouWen Bo SamWBSFaculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada.The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada., Xiang Qun Shi, Younan Liu, Simon D Tran, Francis Beaudry, and Ji Zhang.
• Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada.
• Pain. 2023 Feb 1; 164 (2): e77e90e77-e90.

AbstractNeuropathic pain is a complex, debilitating disease that results from injury to the somatosensory nervous system. The presence of systemic chronic inflammation has been observed in patients with chronic pain but whether it plays a causative role remains unclear. This study aims to determine the perturbation of systemic homeostasis by an injury to peripheral nerve and its involvement in neuropathic pain. We assessed the proteomic profile in the serum of mice at 1 day and 1 month after partial sciatic nerve injury (PSNL) or sham surgery. We also assessed mouse mechanical and cold sensitivity in naïve mice after receiving intravenous administration of serum from PSNL or sham mice. Mass spectrometry-based proteomic analysis revealed that PSNL resulted in a long-lasting alteration of serum proteome, where most of the differentially expressed proteins were in inflammation-related pathways, involving cytokines and chemokines, autoantibodies, and complement factors. Although transferring sham serum to naïve mice did not change their pain sensitivity, PSNL serum significantly lowered mechanical thresholds and induced cold hypersensitivity in naïve mice. With broad anti-inflammatory properties, bone marrow cell extracts not only partially restored serum proteomic homeostasis but also significantly ameliorated PSNL-induced mechanical allodynia, and serum from bone marrow cell extracts-treated PSNL mice no longer induced hypersensitivity in naïve mice. These findings clearly demonstrate that nerve injury has a long-lasting impact on systemic homeostasis, and nerve injury-associated systemic inflammation contributes to the development of neuropathic pain.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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