Calcitonin Gene-Related Peptide and Calcitonin mRNA Expression in Periaqueductal Gray Area in the Formalin Test in Rats

Background: Calcitonin gene-related peptide (CGRP) and rat calcitonin (rCT) play critical roles in descending pain control systems. Objectives: The present research aimed to evaluate the effect of the intracerebroventricular (ICV) administration of CGRP and rCT on the mRNA expression of CGRP and rCT peptides in the periaqueductal gray (PAG) of healthy rats in the formalin test. Methods: A total of 24 male Sprague Dawley rats were categorized into four groups (n = 6). One week after stereotaxic surgery, 1.5 nmol CGRP or rCT peptides were injected (ICV) once daily for 7 days. After 20 min from the last injection, the right foot of the animal was injected subcutaneously with 2.5% formalin. Pain-related behaviors were recorded immediately for 60 min. The PAG nucleus was then removed to assess the changes made in the mRNA expression of the CGRP and rCT. Results: ICV injection of CGRP or rCT reduced pain in the different phases of the trial. ICV injection of rCT induced the expression of rCT mRNA in the PAG area (P < 0.05). However, ICV injection of rCT had no significant effect on the CGRP mRNA expression in the PAG area. Moreover, following the ICV injection of CGRP, the expression of rCT mRNA increased in the PAG area (P < 0.05). It is noteworthy that the ICV injection of CGRP caused a significant effect on the CGRP mRNA expression in the PAG area (P < 0.05). Conclusions: The ICV injections of CGRP and rCT peptides decreased pain in the formalin test. Higher mRNA expression of these peptides in the PAG might be a possible mechanism for this observation.