RESUMEN
The present study was performed to investigate the role of calcitonin gene-related peptide (CGRP) and its receptor in nociception in the basolateral nucleus of amygdala (BLA) of rats. Hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulations were measured by hot plate and Randall Selitto tests. The HWL to both thermal and mechanical stimulations increased significantly after intra-BLA administration of 1.0 or 2.0 nmol CGRP, but not 0.5 nmol, indicating that CGRP plays an anti-nociceptive role in BLA of rats. The anti-nociceptive effect of 1.0 nmol CGRP was blocked significantly by administration of 1.0 or 2.0 nmol CGRP8-37, a selective antagonist of CGRP1 receptor, which suggests that the anti-nociceptive effect of CGRP is mediated by the CGRP1 receptor. Taken together, the results indicate that both CGRP and CGRP1 receptor play important roles in nociceptive modulation in the BLA of rats.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Nociceptores/metabolismo , Dolor/metabolismo , Receptores de Péptido Relacionado con el Gen de Calcitonina/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Animales , Conducta Animal , Péptido Relacionado con Gen de Calcitonina/antagonistas & inhibidores , Péptido Relacionado con Gen de Calcitonina/farmacología , Péptido Relacionado con Gen de Calcitonina/uso terapéutico , Relación Dosis-Respuesta a Droga , Masculino , Nociceptores/citología , Nociceptores/efectos de los fármacos , Dolor/tratamiento farmacológico , Dolor/etiología , Dimensión del Dolor/métodos , Fragmentos de Péptidos/farmacología , Estimulación Física/efectos adversos , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiologíaRESUMEN
The calcitonin receptor-like receptor (CRLR) and the orphan receptor RDC-1 have been proposed to be calcitonin gene-related peptide type 1 (CGRP1) receptors, and receptor activity-modifying proteins (RAMPs) determine the ligand specificity of CRLR. Coexpression of RAMP1 and CRLR resulted in functional CGRP1 receptors; the complex of RAMP2 or RAMP3 and CRLR created functional adrenomedullin receptor. Although high levels of CGRP binding sites in the nucleus accumbens have been reported, little is known about the expression of these novel CGRP receptors. In the present study, we used real-time quantitative RT-PCR to detect and quantitate the relative expression of CGRP, CRLR, RAMP1-3 and RDC-1 in the nucleus accumbens of intact rats and rats with inflammation. Our results demonstrate that CGRP, CRLR, RAMP1 and RAMP2 exist in the nucleus accumbens of intact rats, and that they were significantly upregulated in rats with inflammation. In contrast, no expression was detected for RDC-1 and RAMP3. These findings indicated a functional role for CGRP and its receptors in inflammation and pain modulation.