Preventive Intrathecal Injection of Bupivacaine Alleviated Microglia Activation and Neuropathic Pain in a Rat Model of Chronic Constriction Injury

Autor:	Chih-Cheng Wu, Cheng-Yi Chang, Chung-Yuh Tzeng, Jen-Hsuan Huang, Chih-Jen Hung, Wen-Ying Chen, Su-Lan Liao, Yu-Hsiang Kuan, Chun-Jung Chen
Rok vydání:	2022
Předmět:	Catalysis Inorganic Chemistry Rats Sprague-Dawley Crush Injuries Peripheral Nerve Injuries Animals Physical and Theoretical Chemistry HMGB1 Protein Molecular Biology Spectroscopy Injections Spinal anesthetics microglia neuropathic pain sciatic nerve Organic Chemistry NF-kappa B General Medicine Bupivacaine Constriction Sciatic Nerve Computer Science Applications Rats Toll-Like Receptor 4 Spinal Cord Hyperalgesia Interferon Regulatory Factors Cytokines Neuralgia Microglia Sciatic Neuropathy
Zdroj:	International Journal of Molecular Sciences; Volume 23; Issue 13; Pages: 7197
ISSN:	1422-0067
Popis:	Spinal microglia are crucial to neuronal hyper-excitability and pain hypersensitivity. The local anesthetic bupivacaine is commonly used for both peripheral and spinal anesthesia. The pain-relief effects resulting from the peripheral and systemic administration of bupivacaine have been previously reported. In this study, the preventive effects of intrathecal bupivacaine administration against neuropathic pain were revealed in a rat model of sciatic nerve chronic constriction injury (CCI). Using a CCI rat model, pain hypersensitivity, characterized by mechanical allodynia and thermal hyperalgesia, correlated well with microglia M1 polarization, activation and pro-inflammatory cytokine expression in both spinal cord dorsal horns and sciatic nerves. Bupivacaine attenuated pain behaviors and inflammatory alternations. We further identified that the Interferon Regulatory Factor 5 (IRF5)/P2X Purinoceptor 4 (P2X4R) and High Mobility Group Box 1 (HMGB1)/Toll-Like Receptor 4 (TLR4)/NF-κB inflammatory axes may each play pivotal roles in the acquisition of microglia M1 polarization and pro-inflammatory cytokine expression under CCI insult. The relief of pain paralleled with the suppression of microglia M1 polarization, elevation of microglia M2 polarization, and inhibition of IRF5/P2X4R and HMGB1/TLR4/NF-κB in both the spinal cord dorsal horns and sciatic nerve. Our findings provide molecular and biochemical evidence for the anti-neuropathic effect of preventive bupivacaine.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9aab5ad1c29cf81b6fefaae93234efc7 https://pubmed.ncbi.nlm.nih.gov/35806200 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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