Role of TRPV1 and ASIC3 in formalin-induced secondary allodynia and hyperalgesia.

Abstract

BACKGROUND:

In the present study we determined the role of transient receptor potential V1 channel (TRPV1) and acid-sensing ion channel 3 (ASIC3) in chronic nociception.

METHODS:

1% formalin was used to produce long-lasting secondary allodynia and hyperalgesia in rats. Western blot was used to determine TRPV1 and ASIC3 expression in dorsal root ganglia.

RESULTS:

Peripheral ipsilateral, but not contralateral, pre-treatment (-10min) with the TRPV1 receptor antagonists capsazepine (0.03-0.3μM/paw) and A-784168 (0.01-1μM/paw) prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in the ipsilateral and contralateral paws. Likewise, peripheral ipsilateral, but not contralateral, pre-treatment with the non-selective and selective ASIC3 blocker benzamil (0.1-10μM/paw) and APETx2 (0.02-2μM/paw), respectively, prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Peripheral ipsilateral post-treatment (day 6 after formalin injection) with capsazepine (0.03-0.3μM/paw) and A-784168 (0.01-1μM/paw) reversed 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. In addition, peripheral ipsilateral post-treatment with benzamil (0.1-10μM/paw) and APETx2 (0.02-2μM/paw), respectively, reversed 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. TRPV1 and ASIC3 proteins were expressed in dorsal root ganglion in normal conditions, and 1% formalin injection increased expression of both proteins in this location at 1 and 6 days compared to naive rats.

CONCLUSIONS:

Data suggest that TRPV1 and ASIC3 participate in the development and maintenance of long-lasting secondary allodynia and hyperalgesia induced by formalin in rats. The use of TRPV1 and ASIC3 antagonists by peripheral administration could prove useful to treat chronic pain.

• Authors: Vladimir A Martínez-Rojas, Paulino Barragán-Iglesias, Héctor I Rocha-González, Janet Murbartián, Vinicio Granados-Soto
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 66 Issue 6 Pg. 964-71 (Dec 2014) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 25443722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• 1-(3-(trifluoromethyl)pyridin-2-yl)-N-(4-(trifluoromethylsulfonyl)phenyl)-1,2,3,6-tetrahydropyridine-4-carboxamide
• APETx2 protein, Anthopleura elegantissima
• ASIC3 protein, rat
• Acid Sensing Ion Channels
• Cnidarian Venoms
• Pyridines
• Sulfones
• TRPV Cation Channels
• Trpv1 protein, rat
• benzamil
• Formaldehyde
• Amiloride
• capsazepine
• Capsaicin

Topics

• Acid Sensing Ion Channels (genetics, metabolism)
• Amiloride (administration & dosage, analogs & derivatives, pharmacology)
• Animals
• Blotting, Western
• Capsaicin (administration & dosage, analogs & derivatives, pharmacology)
• Cnidarian Venoms (administration & dosage, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Formaldehyde (toxicity)
• Ganglia, Spinal (metabolism)
• Hyperalgesia (chemically induced, physiopathology, prevention & control)
• Pyridines (administration & dosage, pharmacology)
• Rats
• Sulfones (administration & dosage, pharmacology)
• TRPV Cation Channels (genetics, metabolism)
• Time Factors