Activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) reverses referred mechanical hyperalgesia induced by colonic inflammation in mice.

Abstract

In the current study, we investigated the effect of the activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) on dextran sulphate sodium (DSS)-induced colitis and referred mechanical hyperalgesia in mice. Colitis was induced in CD1 male mice through the intake of 4% DSS in tap water for 7 days. Control mice received unadulterated water. Referred mechanical hyperalgesia was evaluated for 7 days after the beginning of 4% DSS intake. Referred mechanical hyperalgesia started within 1 day after beginning DSS drinking, peaked at 3 days and persisted for 7 days. This time course profile perfectly matched with the appearance of signs of colitis. Both acute and chronic oral treatments with nicotine (0.1-1.0 mg/kg, p.o.) were effective in inhibiting the established referred mechanical hyperalgesia. The antinociceptive effect of nicotine was completely abrogated by cotreatment with the selective α7 nAchR antagonist methyllycaconitine (MLA) (1.0 mg/kg). Consistent with these results, i.p. treatment with the selective α7 nAchR agonist PNU 282987 (0.1-1.0 mg/kg) reduced referred mechanical hyperalgesia at all periods of evaluation. Despite their antinociceptive effects, nicotinic agonists did not affect DSS-induced colonic damage or inflammation. Taken together, the data generated in the present study show the potential relevance of using α7 nAchR agonists to treat referred pain and discomfort associated with inflammatory bowel diseases.

• Authors: Robson Costa, Emerson M Motta, Marianne N Manjavachi, Maíra Cola, João B Calixto
• Journal: Neuropharmacology (Neuropharmacology) Vol. 63 Issue 5 Pg. 798-805 (Oct 2012) ISSN: 1873-7064 [Electronic] England
• PMID: 22722030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Analgesics
• Benzamides
• Bridged Bicyclo Compounds
• Chrna7 protein, mouse
• Nerve Tissue Proteins
• Nicotinic Agonists
• Nicotinic Antagonists
• PNU-282987
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• methyllycaconitine
• Nicotine
• Aconitine

Topics

• Aconitine (adverse effects, analogs & derivatives)
• Analgesics (administration & dosage, antagonists & inhibitors, therapeutic use)
• Animals
• Behavior, Animal (drug effects)
• Benzamides (administration & dosage, therapeutic use)
• Bridged Bicyclo Compounds (administration & dosage, therapeutic use)
• Colitis (chemically induced, immunology, physiopathology)
• Dose-Response Relationship, Drug
• Drug Antagonism
• Hyperalgesia (drug therapy, etiology, immunology)
• Male
• Mice
• Mice, Inbred Strains
• Molecular Targeted Therapy
• Nerve Tissue Proteins (agonists, antagonists & inhibitors, metabolism)
• Nicotine (administration & dosage, antagonists & inhibitors, therapeutic use)
• Nicotinic Agonists (administration & dosage, chemistry, therapeutic use)
• Nicotinic Antagonists (adverse effects)
• Pain Threshold (drug effects)
• Pain, Referred (drug therapy, etiology, immunology)
• Random Allocation
• Receptors, Nicotinic (chemistry, metabolism)
• alpha7 Nicotinic Acetylcholine Receptor