Effects of a chromogranin-derived peptide (CgA 47-66) in the writhing nociceptive response induced by acetic acid in rats

Regul Pept. 2004 Jul 15;119(3):199-207. doi: 10.1016/j.regpep.2004.02.014.


Chromogranin A (CgA) is an acidic protein identified within a large variety of endocrine cells. Colocalized with catecholamines in chromaffin cells, CgA is a prohormone precursor of small biologically active peptides. Vasostatin (CgA 1-76) is the most conserved fragment of CgA and chromogranin A 47-66 peptide (CgA 47-66) possesses potent antimicrobial activities. The aim of this study was to test the hypothesis that CgA 47-66 may be involved in mechanisms modulating nociception. Thus, we used acetic acid (AA) which produces a delayed inflammatory response and episodes of abdominal writhing, a marker of pain, when injected intraperitoneally (i.p.) to rats. Administration (i.p.) of CgA 47-66 induced specific opposite dose-dependent effects depending on concentration. That is, CgA 47-66 below 0.5 mg/kg produced antinociceptive effects, whereas at 2 mg/kg it produced a marked pronociceptive effect. The latter effect was blocked by diltiazem and indomethacin. CgA 47-66-induced antinociceptive effects on AA-induced responses were reversed when the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF 9-41 was i.p. injected to animals prior to AA and CgA 47-66 administration. The administration of i.p. calcitonin gene-related peptide (CGRP) or substance P (SP) evoked dose-dependent abdominal writhing; this effect was abolished when CgA 47-66 was injected. The present data suggest, for the first time, that a fragment of CgA, CgA 47-66, possesses potent antinociceptive effects at low doses. Although the mechanism triggered by this peptide is unknown, CRF receptors are likely to be involved.

MeSH terms

  • Acetic Acid / toxicity*
  • Animals
  • Calcitonin Gene-Related Peptide / administration & dosage
  • Cardiovascular Agents
  • Chromogranin A
  • Chromogranins / administration & dosage*
  • Corticotropin-Releasing Hormone / administration & dosage
  • Diltiazem
  • Dose-Response Relationship, Drug
  • Indomethacin / administration & dosage
  • Male
  • Pain / chemically induced*
  • Pain / drug therapy*
  • Pain / metabolism
  • Pain Management
  • Peptide Fragments / administration & dosage*
  • Rats
  • Rats, Wistar
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Substance P / administration & dosage


  • Cardiovascular Agents
  • Chromogranin A
  • Chromogranins
  • Peptide Fragments
  • Receptors, Corticotropin-Releasing Hormone
  • chromofungin
  • vasostatin I
  • Substance P
  • Corticotropin-Releasing Hormone
  • Diltiazem
  • Calcitonin Gene-Related Peptide
  • Acetic Acid
  • Indomethacin