title: Sodium butyrate and its synthetic amide derivative modulate nociceptive behaviors in mice.
abstract: 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 (10-200mg/Kg) or equimolecular FBA (21.2-424mg/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 (100-200mg/Kg) and FBA (212-424mg/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.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: De Caro
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Avagliano
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cristiano
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: La Rana
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mattace Raso
authors.affiliation: Department of Translational Medicine-Pediatric Section, University of Naples Federico II, Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Berni Canani
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy. Electronic address: meli@unina.it.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meli
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Calignano
mesh_terms: D019342:Acetic Acid; D000577:Amides / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology* / Q000627:therapeutic use; D005557:Formaldehyde; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D007616:Kaolin; D008278:Magnesium Sulfate; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D010812:Physical Stimulation; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000577:Amides; D000700:Analgesics; D000813:Anilides; D047493:PPAR alpha; D047495:PPAR gamma; D020148:Butyric Acid; D005557:Formaldehyde; D007616:Kaolin; D008278:Magnesium Sulfate; D019342:Acetic Acid
keywords: ATP-dependent K+ channel; Chronic constriction injury (CCI); Formalin test; Inflammation; Nociception; Peroxisome proliferator-activated receptor; Sodium butyrate; Visceral pain