INVOLVEMENT OF PROSTAGLANDINS AND CGRP-DEPENDENT SENSORY AFFERENTS INPERITONEAL IRRITATION-INDUCED VISCERAL PAIN

This study investigates the contribution of prostaglandins (PG) and ca lcitonin gene-related peptide (CGRP) pathways in visceral pain induced by peritoneal irritation in rats. Peritoneal irritation was produced by i.p. administration of acetic acid (AA: 0.06-1.0%, 10 ml/kg). Visce ral pain was scored by counting abdominal contractions. The effect of CGRP (3-100 mu g/kg, i.p.) was also evaluated. Like AA, CGRP induced a bdominal pain. Neonatal pretreatment with capsaicin reduced abdominal contractions produced by AA (0.6%) and CGRP (20 mu g/kg) with 64.6% an d 45.6%, respectively. Abdominal contractions induced by AA and CGRP w ere blocked by two antinociceptive drugs, mu-and kappa-opioid agonists , morphine and (+/-)-U-50,488H, respectively, Indomethacin (3 mg/kg, s .c.) reduced the number of abdominal contractions produced by AA by 78 .1%+/-6.4% but did not inhibit abdominal contractions produced by CGRP . The CGRP, receptor antagonist, hCGRP(8-37) (300 mu g/kg, i.v.) inhib ited AA- and CGRP-induced abdominal contractions with 57.5%+/-12.4% an d 51.6%+/-11.3%, respectively. Concomitant i.p. administration of PGE( 1) and PGE(2) (0.3 mg/kg of each) produced abdominal contractions whic h were inhibited 45.6%+/-9.3% by hCGRP(8-37) (300 mu g/kg i.v.). Taken together, these results suggest that peritoneal irritation is likely to trigger the release of prostaglandins, which in turn produces a rel ease of CGRP from primary sensory afferents. (C) 1997 Elsevier Science B.V.