5-HT3a receptor contributes to neuropathic pain by regulating central sensitization in a rat with brachial plexus avulsion

•Mechanical and cold hypersensitivity occurred in the brachial plexus avulsion (BPA) rats.•Immunohistochemistry and western blot revealed the increased expression level of 5-HT3a receptor in spinal dorsal horn neurons and microglia.•Central sensitization and neuroinflammation occurred in spinal dors...

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Veröffentlicht in:Physiology & behavior 2024-04, Vol.277, p.114503-114503, Article 114503
Hauptverfasser: Liao, Chengpeng, Guo, Jinding, Rui, Jing, Gao, Kaiming, Lao, Jie, Zhou, Yingjie
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Sprache:eng
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Zusammenfassung:•Mechanical and cold hypersensitivity occurred in the brachial plexus avulsion (BPA) rats.•Immunohistochemistry and western blot revealed the increased expression level of 5-HT3a receptor in spinal dorsal horn neurons and microglia.•Central sensitization and neuroinflammation occurred in spinal dorsal horn in rats with BPA-induced neuropathic pain.•Blockade of 5-HT3a receptor attenuated mechanical and cold allodynia and central sensitization and neuroinflammation associated with BPA. As a frequently occurring complication resulting from brachial plexus avulsion (BPA), neuropathic pain significantly impacts the quality of life of patients and places a substantial burden on their families. Recent reports have suggested that the 5-HT3a receptor may play a role in the development and regulation of neuropathic pain. The current study aimed to explore the involvement of the 5-HT3a receptor in neuropathic pain resulting from BPA in rats. A rat model of neuropathic pain was induced through brachial plexus avulsion (BPA). The pain thresholds of the rats were measured after BPA. The spinal dorsal horn (SDH) of rats was collected at day 14 after surgery, and the expression and distribution of the 5-HT3a receptor were analyzed using immunohistochemistry and western blotting. The expression levels of various factors related to central sensitization were measured by western blot, including c-Fos, GFAP, IBA-1, IL-1β and TNF-α. The effects of 5-HT3a receptor antagonists on hyperalgesia were assessed through behavioral tests after intrathecal administration of ondansetron. Additionally, at 120 min postinjection, the SDH of rats was acquired, and the change of expression levels of protiens related to central sensitization were measured by western blot. BPA induced mechanical and cold hypersensitivity in rats. The 5-HT3a receptor was increased and mainly distributed on neurons and microglia in the SDH after BPA, and the level of central sensitization and expression of inflammatory factors, such as c-Fos, GFAP, IBA-1, IL-1β and TNF-α, were also increased markedly. Ondansetron, which is a selective 5-HT3a receptor antagonist, reversed the behavioral changes caused by BPA. The antagonist also decreased the expression of central sensitization markers and inflammatory factors. The results suggested that the 5-HT3a receptor is involved in neuropathic pain by regulating central nervous system sensitization in a rat brachial plexus avulsion model. Targeting the 5-HT3a receptor may b
ISSN:0031-9384
1873-507X
DOI:10.1016/j.physbeh.2024.114503