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

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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 (−10 min) with the TRPV1 receptor antagonists capsazepine (0.03–0.3 μM/paw) and A-784168 (0.01–1 μM/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 (0.1–10 μM/paw) and APETx2 (0.02–2 μM/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 (0.03–0.3 μM/paw) and A-784168 (0.01–1 μM/paw) reversed 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. In addition, peripheral ipsilateral post-treatment with benzamil (0.1–10 μM/paw) and APETx2 (0.02–2 μM/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.

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Abbreviations

ANOVA:

analysis of variance

ASICs:

acid-sensing ion channels

ASIC1a:

acid-sensing ion channel 1a

ASIC2:

acid-sensing ion channel 2

ASIC3:

acid-sensing ion channel 3

A-784168:

(1-[3-(trifluoromethyl)pyridin-2-yl]-N-[4-(trifluoromethylsulfonyl)phenyl]-1,2,3,6-tetrahydropyridine-4-carboxamide

Bemzamil:

(N-(benzylamidino)-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride hydrate

CGRP:

calcitonin gene-related peptide

PAGE:

polyacrylamide gel electrophoresis

PVDF:

polyvinylidene difluoride membranes

TRPV1:

transient receptor potential V1 channel

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Authors and Affiliations

  1. Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., México, D.F., Mexico

    Vladimir A. Martínez-Rojas, Paulino Barragán-Iglesias, Janet Murbartián & Vinicio Granados-Soto

  2. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., Mexico

    Héctor I. Rocha-González

Authors
  1. Vladimir A. Martínez-Rojas
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  2. Paulino Barragán-Iglesias
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  3. Héctor I. Rocha-González
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  4. Janet Murbartián
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  5. Vinicio Granados-Soto
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Correspondence to Vinicio Granados-Soto.

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Martínez-Rojas, V.A., Barragán-Iglesias, P., Rocha-González, H.I. et al. Role of TRPV1 and ASIC3 in formalin-induced secondary allodynia and hyperalgesia. Pharmacol. Rep 66, 964–971 (2014). https://doi.org/10.1016/j.pharep.2014.06.011

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  • DOI: https://doi.org/10.1016/j.pharep.2014.06.011

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