Hemopressin, an inverse agonist of cannabinoid receptors, inhibits neuropathic pain in rats

Autor(es)

Toniolo, Elaine F. ^[1] ; Maique, Estefani T. ^[1] ; Ferreira, Jr., Wilson A. ^[2] ; Heimann, Andrea S. ^[3] ; Ferro, Emer S. ^[2] ; Ramos-Ortolaza, Dinah L. ^[4] ; Miller, Lydia ^[4] ; Devi, Lakshmi A. ^[4] ; Dale, Camila S. ^[5]

Afiliação do(s) autor(es)

^[1] Hosp Sirio Libanes, Lab Neuromodulat & Expt Pain, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil

^[3] Proteimax Biotechnol, Cotia - Brazil

^[4] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY - USA

^[5] Univ Sao Paulo, Dept Anat, Lab Neuromodulat & Expt Pain, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Peptides; v. 56, p. 125-131, JUN 2014.
• Citações Web of Science: 18

Resumo

Direct-acting cannabinoid receptor ligands are well known to reduce hyperalgesic responses after nerve injury, although their psychoactive side effects have damped enthusiasm for their therapeutic development. Hemopressin (Hp) is a nonapeptide that selectively binds CBI cannabinoid receptors (031 receptors) and exerts antinociceptive action in inflammatory pain models. We investigated the effect of Hp on neuropathic pain in rats subjected to chronic constriction injury (CCI) of the sciatic nerve, and explored the mechanisms involved. Oral administration of Hp inhibits mechanical hyperalgesia of CCI-rats up to 6h. Hp treatment also decreases Egr-1 immunoreactivity (Egr-1Ir) in the superficial layer of the dorsal horn of the spinal cord of CCI rats. The antinociceptive effect of Hp seems to be independent of inhibitory descending pain pathway since methysergide (5HT(1A) receptor antagonist) and yohimbine (alpha-2 adrenergic receptor antagonist) were unable to prevent Hp antinociceptive effect. Hp decreased calcium flux on DRG neurons from CCI rats, similarly to that observed for AM251, a CB1 receptor antagonist. We also investigated the effect of Hp on potassium channels of CCI rats using UCL 1684 (a blocker of Ca2+-activated K+ channels) which reversed Hp-induced antinociception. Furthermore, concomitant administration of URB-584 (FAAH inhibitor) but not JZL-184 (MAGL inhibitor) potentiates antinociceptive effect of Hp in CCI rats indicating an involvement of anadamide on HP-induced antinociception. Together, these data demonstrate that Hp displays antinociception in pain from neuropathic etiology through local effects. The release of anandamide and the opening of peripheral K+ channels are involved in the antinociceptive effect. (c) 2014 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 09/53404-6 - Estudo dos mecanismos envolvidos no efeito analgésico induzido pela hemopressina em modelo experimental e dor crônica: participação do sistema endocanabinóide e de receptores canabinóides do tipo 1
• Beneficiário: Camila Squarzoni Dale
• Modalidade de apoio: Auxílio à Pesquisa - Regular