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Transient receptor potential channel A1 and noxious cold responses in rat cutaneous nociceptors.
Neuroscience. 2010 Feb 17; 165(4):1412-9.N

Abstract

The role of transient receptor potential channel A1 (TRPA1) in noxious cold sensation remains unclear. Some data support the hypothesis that TRPA1 is a transducer of noxious cold whilst other data contest it. In this study we investigated the role of TRPA1 in cold detection in cutaneous nociceptors in vivo using complementary experimental approaches. We used noxious withdrawal reflex electromyography, and single fibre recordings in vivo, to test the hypothesis that TRPA1-expressing primary afferents mediate noxious cold responses in anaesthetised rats. TRPV1 and TRPM8 agonists sensitise their cognate receptors to heat and cold stimuli respectively. Herein we show that the TRPA1 agonist cinnamaldehyde applied to the skin in anaesthetised rats did not sensitise noxious cold evoked hind limb withdrawal. In contrast, cinnamaldehyde did sensitise the C fibre-mediated noxious heat withdrawal, indicated by a significant drop in the withdrawal temperature. TRPA1 agonist thus sensitised the noxious reflex withdrawal to heat, but not cold. Thermal stimuli also sensitise transient receptor potential (TRP) channels to agonist. Activity evoked by capsaicin in teased primary afferent fibres showed a significant positive correlation with receptive field temperature, in both normal and Freund's complete adjuvant-induced cutaneous inflammation. Altering the temperature of the receptive field did not modulate TRPA1 agonist evoked-activity in cutaneous primary afferents, in either normal or inflamed skin. In addition, block of the TRPA1 channel with Ruthenium Red did not inhibit cold evoked activity in either cinnamaldehyde sensitive or insensitive cold responsive nociceptors. In cinnamaldehyde-sensitive-cold-sensitive afferents, although TRPA1 agonist-evoked activity was totally abolished by Ruthenium Red, cold evoked activity was unaffected by channel blockade. We conclude that these results do not support the hypothesis that TRPA1-expressing cutaneous afferents play an important role in noxious cold responses.

Authors+Show Affiliations

Department of Physiology and Pharmacology, University of Bristol, School of Medical Sciences, University Walk, Bristol, UK.No 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

19961905

Citation

Dunham, J P., et al. "Transient Receptor Potential Channel A1 and Noxious Cold Responses in Rat Cutaneous Nociceptors." Neuroscience, vol. 165, no. 4, 2010, pp. 1412-9.
Dunham JP, Leith JL, Lumb BM, et al. Transient receptor potential channel A1 and noxious cold responses in rat cutaneous nociceptors. Neuroscience. 2010;165(4):1412-9.
Dunham, J. P., Leith, J. L., Lumb, B. M., & Donaldson, L. F. (2010). Transient receptor potential channel A1 and noxious cold responses in rat cutaneous nociceptors. Neuroscience, 165(4), 1412-9. https://doi.org/10.1016/j.neuroscience.2009.11.065
Dunham JP, et al. Transient Receptor Potential Channel A1 and Noxious Cold Responses in Rat Cutaneous Nociceptors. Neuroscience. 2010 Feb 17;165(4):1412-9. PubMed PMID: 19961905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential channel A1 and noxious cold responses in rat cutaneous nociceptors. AU - Dunham,J P, AU - Leith,J L, AU - Lumb,B M, AU - Donaldson,L F, Y1 - 2009/12/01/ PY - 2009/10/21/received PY - 2009/11/24/revised PY - 2009/11/24/accepted PY - 2009/12/8/entrez PY - 2009/12/8/pubmed PY - 2010/3/13/medline SP - 1412 EP - 9 JF - Neuroscience JO - Neuroscience VL - 165 IS - 4 N2 - The role of transient receptor potential channel A1 (TRPA1) in noxious cold sensation remains unclear. Some data support the hypothesis that TRPA1 is a transducer of noxious cold whilst other data contest it. In this study we investigated the role of TRPA1 in cold detection in cutaneous nociceptors in vivo using complementary experimental approaches. We used noxious withdrawal reflex electromyography, and single fibre recordings in vivo, to test the hypothesis that TRPA1-expressing primary afferents mediate noxious cold responses in anaesthetised rats. TRPV1 and TRPM8 agonists sensitise their cognate receptors to heat and cold stimuli respectively. Herein we show that the TRPA1 agonist cinnamaldehyde applied to the skin in anaesthetised rats did not sensitise noxious cold evoked hind limb withdrawal. In contrast, cinnamaldehyde did sensitise the C fibre-mediated noxious heat withdrawal, indicated by a significant drop in the withdrawal temperature. TRPA1 agonist thus sensitised the noxious reflex withdrawal to heat, but not cold. Thermal stimuli also sensitise transient receptor potential (TRP) channels to agonist. Activity evoked by capsaicin in teased primary afferent fibres showed a significant positive correlation with receptive field temperature, in both normal and Freund's complete adjuvant-induced cutaneous inflammation. Altering the temperature of the receptive field did not modulate TRPA1 agonist evoked-activity in cutaneous primary afferents, in either normal or inflamed skin. In addition, block of the TRPA1 channel with Ruthenium Red did not inhibit cold evoked activity in either cinnamaldehyde sensitive or insensitive cold responsive nociceptors. In cinnamaldehyde-sensitive-cold-sensitive afferents, although TRPA1 agonist-evoked activity was totally abolished by Ruthenium Red, cold evoked activity was unaffected by channel blockade. We conclude that these results do not support the hypothesis that TRPA1-expressing cutaneous afferents play an important role in noxious cold responses. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/19961905/Transient_receptor_potential_channel_A1_and_noxious_cold_responses_in_rat_cutaneous_nociceptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(09)01976-9 DB - PRIME DP - Unbound Medicine ER -