Calcitonin-gene related peptide is a potent inducer of oedema in rat orofacial tissue

Background and aims: This study aimed to assess the potential of calcitonin-gene related peptide (CGRP), a neuropeptide released from sensory nerves, to induce oedema in orofacial tissue. Experimental approach: Wistar rats (150-200 g) anesthetized with isoflurane were injected intraorally with CGRP (100 mu l; 8-33 pmol) in the right side of the mouth. The contralateral side was injected with the same volume of physiological saline. Increased cheek thickness (in mm), as a measure of oedema formation, was assayed bilaterally with a digital caliper before (T = 0) and up to 24 h following injection of CGRP. Pretreatment with antagonists (CGRP(8-37), 10 nmol; pizotifen, 2 mg/Ag) was given by intra-oral or subcutaneous injection, 10 or 30 min, respectively, before the inflammatory stimulus. CGRP and CGRP(8-37) were also injected into the rat hind paw to induce oedema. Data are presented as the mean (+/- SEM) difference in thickness between the right and the left sides at each time. Results: Following intra-oral injection, CGRP induced a rapidly developing (5-15 min) and long-lasting (6 h), dose-dependent oedema in the rat cheek, blocked by pre-treatment with CGRP(8-37) or pizotifen. CGRP induced a smaller oedematogenic effect in the rat hind paw also blocked by the CGRP antagonist. CGRP (16 pmol) potentiated the oedema induced by co-injected substance P (3.7 nmol) and contributed to the oedema following intraoral injection of carrageenan (100 mu g). Injection of CGRP(8-37) alone induced an early but short-lasting oedema. Conclusion: Local injection of CGRP potently induced oedema in the orofacial tissue of rats which was blocked by a CGRP receptor antagonist. The overall inhibition of carrageenan-induced oedema by CGRP(8-37) suggests that endogenous CGRP contributes to an oedematogenic response in orofacial tissues.