The effect of a chromogranin A-derived peptide (CgA4-16) in the writhing nociceptive response induced by acetic acid in rats.
The nociceptive effects of i.p administration of a synthetic peptide (CgA4-16) derived from chromogranin A (CgA) were studied on a model of inflammatory (somato-visceral) pain. Inflammatory mediators participate in controlling the activity of enterochromaffin cells that store and release chromogranins. Adult male Wistar rats were injected i.p with diluted acetic acid (AA) to induce abdominal writhes. Pharmacological agents were injected prior to CgA4-16 and/or AA together. While i.p CgA4-16 alone did not produce any effect, the peptide increased the number of abdominal constrictions induced by i.p AA administration in a dose-related manner. To determine the possible mechanisms involved in CgA4-16 produced pronociceptive effect, i.p diltiazem or indomethacin were tested. The pronociceptive effect induced by CgA4-16 was blocked by pretreatment of either substance. I.p administration of CGRP, substance P (SP) or capsaicin evoked dose-related abdominal writhing. CgA4-16, 20 min prior to CGRP or capsaicin, potentiated the nociceptive effects induced by CGRP or capsaicin, but not those induced by SP. Taken together, these data suggest for the first time that a CgA-derived peptide may modulate inflammatory pain.
INSERM U575, Hôpital Civil Pavillon Poincaré, 1, place de l'Hôpital, 67091 Strasbourg, France.
Jean-Eric
JE
Ghia
Francis
F
Crenner
Marie-Hélène
MH
Metz-Boutigue
Dominique
D
Aunis
Fabielle
F
Angel
D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D053379:Chromogranin A; D002864:Chromogranins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D010147:Pain Measurement / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C489882:chromogranin A (4-16); C506153:chromogranin A, rat; D013373:Substance P; D004110:Diltiazem; D015740:Calcitonin Gene-Related Peptide; D019342:Acetic Acid; D002211:Capsaicin; D007213:Indomethacin