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Primary afferents with TRPM8 and TRPA1 profiles target distinct subpopulations of rat superficial dorsal horn neurones.

作者信息

Wrigley Paul J, Jeong Hyo-Jin, Vaughan Christopher W

机构信息

Pain Management Research Institute, Kolling Institute, Level 13, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia.

出版信息

Br J Pharmacol. 2009 Jun;157(3):371-80. doi: 10.1111/j.1476-5381.2009.00167.x. Epub 2009 Apr 3.

DOI:10.1111/j.1476-5381.2009.00167.x
PMID:19371346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2707984/
Abstract

BACKGROUND AND PURPOSE: The transient receptor potential (TRP) channels, transient receptor potential melastatin-1 (TRPM8) and transient receptor potential ankyrin-1 (TRPA1), are expressed in subpopulations of sensory neurones and have been proposed to mediate innocuous and noxious cold sensation respectively. The aim of this study was to compare TRPM8 and TRPA1 modulation of glutamatergic afferent transmission within the spinal dorsal horn. EXPERIMENTAL APPROACH: Whole cell patch clamp recordings were made from rat spinal cord slices in vitro to examine the effect of TRP agonists and temperature on glutamatergic excitatory postsynaptic currents (EPSCs). KEY RESULTS: Icilin (3 or 100 micromol.L(-1)), menthol (200 micromol.L(-1)) and capsaicin (1 micromol.L(-1)) reduced the amplitude of primary afferent evoked EPSCs in subpopulations of lamina I and II neurones. In a subpopulation of superficial neurones, innocuous cold (threshold 29 degrees C), 3 micromol.L(-1) icilin (EC50 1.5 micromol.L(-1)) and menthol (EC50 263 micromol.L(-1)) increased the rate of spontaneous miniature EPSCs. In the majority of lamina I and II neurones, 100 micromol.L(-1) icilin (EC50 79 micromol.L(-1)), allyl isothiocyanate (EC50 226 micromol.L(-1)), cinnamaldehyde (EC50 38 micromol.L(-1)) and capsaicin (1 micromol.L(-1)) increased miniature EPSC rate. The response to 100 micromol.L(-1), but not 3 micromol.L(-1) icilin, was abolished by ruthenium red, while neither was affected by iodoresiniferatoxin. Responsiveness to 3 micromol.L(-1), but not to 100 micromol.L(-1) icilin, was highly predictive of innocuous cold responsiveness. Neurones responding to 3 micromol.L(-1) icilin and innocuous cold were located more superficially than those responding to 100 micromol.L(-1) icilin. CONCLUSIONS AND IMPLICATIONS: Activation of TRPM8 and TRPA1 presynaptically modulated glutamatergic transmission onto partially overlapping but distinct populations of superficial dorsal horn neurones. Spinal TRPM8 and TRPA1 channels may therefore provide therapeutic targets in cold hyperesthesia.

摘要

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本文引用的文献

[1]
Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1.

Mol Pain. 2008-7-31

[2]
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Pain Med. 2008-4

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Guide to Receptors and Channels (GRAC), 3rd edition.

Br J Pharmacol. 2008-3

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Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress.

J Neurosci. 2008-3-5

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Visualizing cold spots: TRPM8-expressing sensory neurons and their projections.

J Neurosci. 2008-1-16

[6]
Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons.

J Neurosci. 2007-12-19

[7]
A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition.

Mol Pain. 2007-12-17

[8]
TRPM8 mechanism of cold allodynia after chronic nerve injury.

J Neurosci. 2007-12-12

[9]
Bimodal action of menthol on the transient receptor potential channel TRPA1.

J Neurosci. 2007-9-12

[10]
TRPA1 mediates formalin-induced pain.

Proc Natl Acad Sci U S A. 2007-8-14

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