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Roles of cutaneous versus spinal TRPA1 channels in mechanical hypersensitivity in the diabetic or mustard oil-treated non-diabetic rat.
Neuropharmacology. 2010 Mar; 58(3):578-84.N

Abstract

Previous results indicate that intaperitoneal administration of a TRPA1 channel antagonist attenuates diabetic hypersensitivity. We studied whether the antihypersensitivity effect induced by a TRPA1 channel antagonist in diabetic animals is explained by action on the TRPA1 channel in the skin, the spinal cord, or both. For comparison, we determined the contribution of cutaneous and spinal TRPA1 channels to development of hypersensitivity induced by topical administration of mustard oil in healthy controls. Diabetes mellitus was induced by streptozotocin in the rat. Hypersensitivity was assessed by the monofilament- and paw pressure-induced limb withdrawal response. Intrathecal (i.t.) administration of Chembridge-5861528 (CHEM, a TRPA1 channel antagonist) at doses 2.5-5.0 microg/rat markedly attenuated diabetic hypersensitivity, whereas 20 microg of CHEM was needed to produce a weak attenuation of diabetic hypersensitivity with intraplantar (i.pl.) administrations. In controls, i.pl. administration of CHEM (20 microg) produced a weak antihypersensitivity effect at the mustard oil-treated site. I.t. administration of CHEM (10 microg) in controls produced a strong antihypersensitivity effect adjacent to the mustard oil-treated area (site of secondary hyperalgesia), while it failed to influence hypersensitivity at the mustard oil-treated area (site of primary hyperalgesia). A reversible antagonism of the rat TRPA1 channel by CHEM was verified using in vitro patch clamp recordings. The results suggest that while cutaneous TRPA1 channels contribute to mechanical hypersensitivity induced by diabetes or topical mustard oil, spinal TRPA1 channels, probably on central terminals of primary afferent nerve fibers, play an important role in maintenance of mechanical hypersensitivity in these conditions.

Authors+Show Affiliations

Institute of Biomedicine/Physiology, University of Helsinki, Biomedicum Helsinki, POB 63, 00014 Helsinki, Finland.No 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

20004676

Citation

Wei, Hong, et al. "Roles of Cutaneous Versus Spinal TRPA1 Channels in Mechanical Hypersensitivity in the Diabetic or Mustard Oil-treated Non-diabetic Rat." Neuropharmacology, vol. 58, no. 3, 2010, pp. 578-84.
Wei H, Chapman H, Saarnilehto M, et al. Roles of cutaneous versus spinal TRPA1 channels in mechanical hypersensitivity in the diabetic or mustard oil-treated non-diabetic rat. Neuropharmacology. 2010;58(3):578-84.
Wei, H., Chapman, H., Saarnilehto, M., Kuokkanen, K., Koivisto, A., & Pertovaara, A. (2010). Roles of cutaneous versus spinal TRPA1 channels in mechanical hypersensitivity in the diabetic or mustard oil-treated non-diabetic rat. Neuropharmacology, 58(3), 578-84. https://doi.org/10.1016/j.neuropharm.2009.12.001
Wei H, et al. Roles of Cutaneous Versus Spinal TRPA1 Channels in Mechanical Hypersensitivity in the Diabetic or Mustard Oil-treated Non-diabetic Rat. Neuropharmacology. 2010;58(3):578-84. PubMed PMID: 20004676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of cutaneous versus spinal TRPA1 channels in mechanical hypersensitivity in the diabetic or mustard oil-treated non-diabetic rat. AU - Wei,Hong, AU - Chapman,Hugh, AU - Saarnilehto,Marja, AU - Kuokkanen,Katja, AU - Koivisto,Ari, AU - Pertovaara,Antti, Y1 - 2009/12/29/ PY - 2009/09/15/received PY - 2009/11/11/revised PY - 2009/12/01/accepted PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/4/8/medline SP - 578 EP - 84 JF - Neuropharmacology JO - Neuropharmacology VL - 58 IS - 3 N2 - Previous results indicate that intaperitoneal administration of a TRPA1 channel antagonist attenuates diabetic hypersensitivity. We studied whether the antihypersensitivity effect induced by a TRPA1 channel antagonist in diabetic animals is explained by action on the TRPA1 channel in the skin, the spinal cord, or both. For comparison, we determined the contribution of cutaneous and spinal TRPA1 channels to development of hypersensitivity induced by topical administration of mustard oil in healthy controls. Diabetes mellitus was induced by streptozotocin in the rat. Hypersensitivity was assessed by the monofilament- and paw pressure-induced limb withdrawal response. Intrathecal (i.t.) administration of Chembridge-5861528 (CHEM, a TRPA1 channel antagonist) at doses 2.5-5.0 microg/rat markedly attenuated diabetic hypersensitivity, whereas 20 microg of CHEM was needed to produce a weak attenuation of diabetic hypersensitivity with intraplantar (i.pl.) administrations. In controls, i.pl. administration of CHEM (20 microg) produced a weak antihypersensitivity effect at the mustard oil-treated site. I.t. administration of CHEM (10 microg) in controls produced a strong antihypersensitivity effect adjacent to the mustard oil-treated area (site of secondary hyperalgesia), while it failed to influence hypersensitivity at the mustard oil-treated area (site of primary hyperalgesia). A reversible antagonism of the rat TRPA1 channel by CHEM was verified using in vitro patch clamp recordings. The results suggest that while cutaneous TRPA1 channels contribute to mechanical hypersensitivity induced by diabetes or topical mustard oil, spinal TRPA1 channels, probably on central terminals of primary afferent nerve fibers, play an important role in maintenance of mechanical hypersensitivity in these conditions. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/20004676/Roles_of_cutaneous_versus_spinal_TRPA1_channels_in_mechanical_hypersensitivity_in_the_diabetic_or_mustard_oil_treated_non_diabetic_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(09)00367-0 DB - PRIME DP - Unbound Medicine ER -