Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive potassium channels pathway

Autor(es)

Kusuda, Ricardo ^[1] ; Carreira, Eleonora Uchoa ^[1] ; Ulloa, Luis ^[2] ; Cunha, Fernando Queiroz ^[1] ; Kanashiro, Alexandre ^[3] ; Cunha, Thiago Mattar ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[2] Duke Univ, Dept Anesthesiol, Ctr Perioperat Organ Protect, Durham, NC 27710 - USA

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brain Research; v. 1727, JAN 15 2020.
• Citações Web of Science: 0

Resumo

New findings on neural regulation of immunity are allowing the design of novel pharmacological strategies to control inflammation and nociception. Herein, we report that choline, a 7-nicotinic acetylcholine receptor (alpha 7nAChRs) agonist, prevents carrageenan-induced hyperalgesia without affecting inflammatory parameters (neutrophil migration or cytokine/chemokines production) or inducing sedation or even motor impairment. Choline also attenuates prostaglandin-E-2 (PGE(2))-induced hyperalgesia via alpha 7nAChR activation and this antinociceptive effect was abrogated by administration of LNMMA (a nitric oxide synthase inhibitor), ODQ (an inhibitor of soluble guanylate cyclase; cGMP), and glibenclamide (an inhibitor of ATP-sensitive potassium channels). Furthermore, choline attenuates long-lasting Complete Freunds Adjuvant and incision-induced hyperalgesia suggesting its therapeutic potential to treat pain in rheumatoid arthritis or post-operative recovery, respectively. Our results suggest that choline modulates inflammatory hyperalgesia by activating the nitric oxide/cGMP/ATP-sensitive potassium channels without interfering in inflammatory events, and could be used in persistent pain conditions. (AU)

• Processo FAPESP: 12/23846-0 - Papel da via succinato/GPR91 na fisiopatologia da dor crônica de origem neuropática
• Beneficiário: Ricardo Kusuda
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/20343-4 - Via colinérgica anti-inflamatória: o papel da neuroimunomodulação no controle da resposta inflamatória
• Beneficiário: Alexandre Kanashiro
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 10/16823-8 - Investigação dos mecanismos envolvidos no efeito analgésico da colina.
• Beneficiário: Eleonora Uchôa Carreira
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica