Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel

Autor:	Ya-Kun Huang, Zuo-Jie Jiang, Jian-Xin Shen, Xin Zhao, Xiao-Man Wu, Feng-Ming Zhang, Jing-Bing Zhang, Qing-Yi Li, Yong Chen, Jia-Hui Gu, Xing-Jun Liu, Yu-Gang Lu, Yanli Liu, Ling-Bo Bi
Rok vydání:	2020
Předmět:	0301 basic medicine Male medicine.medical_specialty animal structures medicine.medical_treatment TRPV1 TRPV Cation Channels Rodentia Rats Sprague-Dawley 03 medical and health sciences Mice 0302 clinical medicine Dorsal root ganglion Peripheral Nerve Injuries Internal medicine Ganglia Spinal medicine Animals Pharmacology business.industry Research Papers Activins Rats 030104 developmental biology medicine.anatomical_structure Nociception Endocrinology Hyperalgesia Neuropathic pain Peripheral nerve injury embryonic structures Cytokines Neuralgia Sciatic nerve Axotomy medicine.symptom business 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists
Zdroj:	Br J Pharmacol
ISSN:	1476-5381
Popis:	Background and purpose The cytokine activin C is mainly expressed in small-diameter dorsal root ganglion (DRG) neurons and suppresses inflammatory pain. However, the effects of activin C in neuropathic pain remain elusive. Experimental approach Male rats and wild-type and TRPV1 knockout mice with peripheral nerve injury - sciatic nerve axotomy and spinal nerve ligation in rats; chronic constriction injury (CCI) in mice - provided models of chronic neuropathic pain. Ipsilateral lumbar (L)4-5 DRGs were assayed for activin C expression. Chronic neuropathic pain animals were treated with intrathecal or locally pre-administered activin C or the vehicle. Nociceptive behaviours and pain-related markers in L4-5 DRGs and spinal cord were evaluated. TRPV1 channel modulation by activin C was measured. Key results Following peripheral nerve injury, expression of activin βC subunit mRNA and activin C protein was markedly up-regulated in L4-5 DRGs of animals with axotomy, SNL or CCI. [Correction added on 26 November 2020, after first online publication: The preceding sentence has been corrected in this current version.] Intrathecal activin C dose-dependently inhibited neuropathic pain in spinal nerve ligated rats. Local pre-administration of activin C decreased neuropathic pain, macrophage infiltration into ipsilateral L4-5 DRGs and microglial reaction in L4-5 spinal cords of mice with CCI. In rat DRG neurons, activin C enhanced capsaicin-induced TRPV1 currents. Pre-treatment with activin C reduced capsaicin-evoked acute hyperalgesia and normalized capsaicin-evoked persistent hypothermia in mice. Finally, the analgesic effect of activin C was abolished in TRPV1 knockout mice with CCI. Conclusion and implications Activin C inhibits neuropathic pain by modulating TRPV1 channels, revealing potential analgesic applications in chronic neuropathic pain therapy.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::590169e3c32a8f14d517ed1531607987 https://pubmed.ncbi.nlm.nih.gov/33095918 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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