Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice

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• 作者：Roberto Russo^a ; Carmen De Caro^a ; Carmen Avagliano^a ; Claudia Cristiano^a ; Giovanna La Rana^a ; Giuseppina Mattace Raso^a ; Roberto Berni Canani^b ; Rosaria Meli^a ; ^{meli@unina.it" class="auth_mail" title="E-mail the corresponding author} ; Antonio Calignano^a
• 关键词：SCFA ; short-chain fatty acid ; HDAC ; histone deacetylases ; GPR41 and GPR43 respectively ; free fatty acid receptor (FFAR)-2 and 3 ; PPARs ; peroxisome proliferator-activated receptors ; MTC1 ; monocarboxylate transporter 1 ; CCI ; chronic constriction injury ; FBA ; N-(1-carbamoyl-2-phenyl-ethyl) butyramide ; IBS ; irritable bowel syndrome ; EGTA ; ethyleneglycol-bis (β-aminoethyl)-N ; N ; N&prime ; N&prime ; -tetraacetic acid ; EDTA ; ethylenediaminetetraacetic acid ; PMSF ; phenylmethylsulphonylfluoride ; COX-2 ; cycloo
• 刊名：Pharmacological Research
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：103
• 期：Complete
• 页码：279-291
• 全文大小：2621 K

文摘

In the present study we investigated the role of sodium butyrate (butyrate), and its more palatable derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), in animal models of acute and chronic pain. We found that oral administrations of butyrate (10–200 mg/Kg) or equimolecular FBA (21.2–424 mg/Kg) reduced visceral pain in a dose- and time-dependent manner. Both drugs were also effective in the formalin test, showing an antinociceptive effect. This analgesic effect was blocked by glibenclamide, suggesting the involvement of ATP-dependent K⁺ channels. Moreover, following repeated administration butyrate (100–200 mg/Kg) and FBA (212–424 mg/Kg) retained their analgesic properties in a model of neuropathic pain, reducing mechanical and thermal hyperalgesia in the chronic constriction injury (CCI) model. The involvement of peroxisome proliferator-activated receptor (PPAR) -α and -γ for the analgesic effect of butyrate was also investigated by using PPAR-α null mice or the PPAR-γ antagonist GW9662. Western blot analysis, confirmed the role of peroxisome receptors in butyrate effects, evidencing the increase of PPAR-α and -γ expression, associated to the reduction of inflammatory markers (COX-2, iNOS, TNF-α and cFOS).

In conclusion, we describe the role of butyrate-based drugs in pain, identifying different and converging non-genomic and genomic mechanisms of action, which cooperate in nociception maintenance.