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Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat.
Pain. 2011 Mar; 152(3):582-91.PAIN

Abstract

The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed on nociceptive primary afferent neurons. On the proximal nerve ending within the spinal dorsal horn, TRPA1 regulates transmission to spinal interneurons, and thereby pain hypersensitivity. Here we assessed whether the contribution of the spinal TRPA1 channel to pain hypersensitivity varies with the experimental pain model, properties of test stimulation or the behavioral pain response. The antihypersensitivity effect of intrathecally (i.t.) administered Chembridge-5861528 (CHEM; a selective TRPA1 channel antagonist; 5-10μg) was determined in various experimental models of pain hypersensitivity in the rat. In spinal nerve ligation and rapid eye movement (REM) sleep deprivation models, i.t. CHEM attenuated mechanical hypersensitivity. Capsaicin-induced secondary (central) but not primary (peripheral) mechanical hypersensitivity was also reduced by i.t. administration of CHEM or A-967079, another TRPA1 channel antagonist. Formalin-induced secondary mechanical hypersensitivity, but not spontaneous pain, was suppressed by i.t. CHEM. Moreover, mechanical hypersensitivity induced by cholekystokinin in the rostroventromedial medulla was attenuated by i.t. pretreatment with CHEM. Independent of the model, the antihypersensitivity effect induced by i.t. CHEM was predominant on responses evoked by low-intensity stimuli (⩽6g). CHEM (10μg i.t.) failed to attenuate pain behavior in healthy controls or mechanical hypersensitivities induced by i.t. administrations of a GABA(A) receptor antagonist, or NMDA or 5-HT(3) receptor agonists. Conversely, i.t. administration of a TRPA1 channel agonist, cinnamon aldehyde, induced mechanical hypersensitivity. The results indicate that the spinal TRPA1 channel exerts an important role in secondary (central) pain hypersensitivity to low-intensity mechanical stimulation in various pain hypersensitivity conditions. The spinal TRPA1 channel provides a promising target for the selective attenuation of a central mechanism contributing to pathophysiological pain.

Authors+Show Affiliations

Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21211906

Citation

Wei, Hong, et al. "Spinal Transient Receptor Potential Ankyrin 1 Channel Contributes to Central Pain Hypersensitivity in Various Pathophysiological Conditions in the Rat." Pain, vol. 152, no. 3, 2011, pp. 582-91.
Wei H, Koivisto A, Saarnilehto M, et al. Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat. Pain. 2011;152(3):582-91.
Wei, H., Koivisto, A., Saarnilehto, M., Chapman, H., Kuokkanen, K., Hao, B., Huang, J. L., Wang, Y. X., & Pertovaara, A. (2011). Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat. Pain, 152(3), 582-91. https://doi.org/10.1016/j.pain.2010.11.031
Wei H, et al. Spinal Transient Receptor Potential Ankyrin 1 Channel Contributes to Central Pain Hypersensitivity in Various Pathophysiological Conditions in the Rat. Pain. 2011;152(3):582-91. PubMed PMID: 21211906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal transient receptor potential ankyrin 1 channel contributes to central pain hypersensitivity in various pathophysiological conditions in the rat. AU - Wei,Hong, AU - Koivisto,Ari, AU - Saarnilehto,Marja, AU - Chapman,Hugh, AU - Kuokkanen,Katja, AU - Hao,Bin, AU - Huang,Jin-Lu, AU - Wang,Yong-Xiang, AU - Pertovaara,Antti, Y1 - 2011/01/05/ PY - 2010/10/12/received PY - 2010/11/29/accepted PY - 2011/1/8/entrez PY - 2011/1/8/pubmed PY - 2011/6/17/medline SP - 582 EP - 91 JF - Pain JO - Pain VL - 152 IS - 3 N2 - The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed on nociceptive primary afferent neurons. On the proximal nerve ending within the spinal dorsal horn, TRPA1 regulates transmission to spinal interneurons, and thereby pain hypersensitivity. Here we assessed whether the contribution of the spinal TRPA1 channel to pain hypersensitivity varies with the experimental pain model, properties of test stimulation or the behavioral pain response. The antihypersensitivity effect of intrathecally (i.t.) administered Chembridge-5861528 (CHEM; a selective TRPA1 channel antagonist; 5-10μg) was determined in various experimental models of pain hypersensitivity in the rat. In spinal nerve ligation and rapid eye movement (REM) sleep deprivation models, i.t. CHEM attenuated mechanical hypersensitivity. Capsaicin-induced secondary (central) but not primary (peripheral) mechanical hypersensitivity was also reduced by i.t. administration of CHEM or A-967079, another TRPA1 channel antagonist. Formalin-induced secondary mechanical hypersensitivity, but not spontaneous pain, was suppressed by i.t. CHEM. Moreover, mechanical hypersensitivity induced by cholekystokinin in the rostroventromedial medulla was attenuated by i.t. pretreatment with CHEM. Independent of the model, the antihypersensitivity effect induced by i.t. CHEM was predominant on responses evoked by low-intensity stimuli (⩽6g). CHEM (10μg i.t.) failed to attenuate pain behavior in healthy controls or mechanical hypersensitivities induced by i.t. administrations of a GABA(A) receptor antagonist, or NMDA or 5-HT(3) receptor agonists. Conversely, i.t. administration of a TRPA1 channel agonist, cinnamon aldehyde, induced mechanical hypersensitivity. The results indicate that the spinal TRPA1 channel exerts an important role in secondary (central) pain hypersensitivity to low-intensity mechanical stimulation in various pain hypersensitivity conditions. The spinal TRPA1 channel provides a promising target for the selective attenuation of a central mechanism contributing to pathophysiological pain. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/21211906/Spinal_transient_receptor_potential_ankyrin_1_channel_contributes_to_central_pain_hypersensitivity_in_various_pathophysiological_conditions_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(10)00716-5 DB - PRIME DP - Unbound Medicine ER -