Implication of the calcitonin gene-related peptide and its receptor binding sites in animal models of chronic pain

Calcitonin gene-related peptide (CGRP) is a 37 amino acid peptide arising from the alternative splicing of the calcitonin gene. The wide distribution of CGRP in the central and peripheral nervous systems suggests a role for CGRP in sensory processing. The primary focus of, this thesis was to study the involvement of CGRP and its binding sites in rat models of chronic inflammatory and neuropathic pain. The expression and binding sites of galanin and substance P were also examined to assess the specificity of the observed changes.No changes were observed in CGRP, galanin and substance P immunostaining in the dorsal horn of the lumbar regions 4 and 5 (L4--L5) of the spinal cord at 24 hours, 4, 7 and 14 days following the injection of Freund's complete adjuvant or sciatic nerve constriction. However, binding sites at the L4--L5 levels were found to be modulated during the development of chronic pain. CGRP binding sites were found to be increased and decreased in models of inflammatory and neuropathic pain, respectively. Substance P binding sites were increased in both models while galanin binding sites were decreased only in this neuropathy pain model.In conclusion, the changes in CGRP binding levels observed following the injection of Freund's complete adjuvant or constriction of the sciatic nerve were not mirrored by similar changes in substance P and galanin binding sites. This finding indicates differential involvement of these neuropeptides and their receptors in chronic pain mechanisms