Involvement of prostaglandins and CGRP-dependent sensory afferents in peritoneal irritation-induced visceral pain.
This study investigates the contribution of prostaglandins (PG) and calcitonin 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). Visceral pain was scored by counting abdominal contractions. The effect of CGRP (3-100 microg/kg, i.p.) was also evaluated. Like AA, CGRP induced abdominal pain. Neonatal pretreatment with capsaicin reduced abdominal contractions produced by AA (0.6%) and CGRP (20 microg/kg) with 64.6% and 45.6%, respectively. Abdominal contractions induced by AA and CGRP were 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 microg/kg, i.v.) inhibited AA- and CGRP-induced abdominal contractions with 57.5%+/-12.4% and 51.6%+/-11.3%, respectively. Concomitant i.p. administration of PGE1 and PGE2 (0.3 mg/kg of each) produced abdominal contractions which were inhibited 45.6%+/-9.3% by hCGRP(8-37) (300 microg/kg i.v.). Taken together, these results suggest that peritoneal irritation is likely to trigger the release of prostaglandins, which in turn produces a release of CGRP from primary sensory afferents.
Friese
N
N
Institut de Recherche Jouveinal, Fresnes, France.
Diop
L
L
Chevalier
E
E
Angel
F
F
Rivière
P J
PJ
Dahl
S G
SG
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D019342:Acetic Acid / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D003085:Colic / Q000139:chemically induced* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010537:Peritoneum / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014781:Viscera / Q000187:drug effects* / Q000294:innervation
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011759:Pyrrolidines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D015740:Calcitonin Gene-Related Peptide; D019342:Acetic Acid; D002211:Capsaicin; D007213:Indomethacin