Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with aδ/c‐fibers and colocalization with trk receptors

Abstract

The transient receptor potential (TRP) superfamily of cation channels contains four temperature-sensitive channels, named TRPV1-4, that are activated by heat stimuli from warm to that in the noxious range. Recently, two other members of this superfamily, TRPA1 and TRPM8, have been cloned and characterized as possible candidates for cold transducers in primary afferent neurons. Using in situ hybridization histochemistry and immunohistochemistry, we characterized the precise distribution of TRPA1, TRPM8, and TRPV1 mRNAs in the rat dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons. In the DRG, TRPM8 mRNA was not expressed in the TRPV1-expressing neuronal population, whereas TRPA1 mRNA was only seen in some neurons in this population. Both A-fiber and C-fiber neurons expressed TRPM8, whereas TRPV1 was almost exclusively seen in C-fiber neurons. All TRPM8-expressing neurons also expressed TrkA, whereas the expression of TRPV1 and TRPA1 was independent of TrkA expression. None of these three TRP channels were coexpressed with TrkB or TrkC. The TRPM8-expressing neurons were more abundant in the TG compared with the DRG, especially in the mandibular nerve region innervating the tongue. Our data suggest heterogeneity of TRPM8 and TRPA1 expression by subpopulations of primary afferent neurons, which may result in the difference of cold-sensitive primary afferent neurons in sensitivity to chemicals such as menthol and capsaicin and nerve growth factor.

Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord

“…We have previously shown that neonatal degeneration of TRPV1-expressing sensory nerves increased salt sensitivity of arterial pressure as these rats grew into adulthood [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] . However, the systemic sensory denervation used in these previous studies precluded us from making conclusions about whether the observed effect was due to the removal of TRPV1 or other proteins co-expressed in the same nerves innervating any specific organs or tissues [21,22] . In the present study, we anatomically limited the TRPV1 affected by intrathecally injecting TRPV1 shRNA to selectively knockdown TRPV1 in an attempt to answer the question of whether impairment of TRPV1 in selective tissues is suffi cient to enhance salt sensitivity of blood pressure.…”

“…Our previous approach using systemic sensory denervation does, however, have two major limitations. First, systemic sensory denervation obliterates not only TRPV1 but also other components that colocalize with TRPV1 in the same neuron, which may regulate blood pressure independently of TRPV1 [21,22] . Second, systemic sensory denervation prevents elucidation of the role of specifi c organ(s) or tissue(s) in regulating blood pressure.…”

Diversity in the Neural Circuitry of Cold Sensing Revealed by Genetic Axonal Labeling of Transient Receptor Potential Melastatin 8 Neurons

“…2a, available at www. jneurosci.org as supplemental material) (Peier et al, 2002;Abe et al, 2005;Kobayashi et al, 2005). However, a number of Trpm8 GFP neurons (Fig.…”

“…Indeed, the paucity of neurons that express TRPM8 has made the study of this thermosensor and these cells problematic at best. TRPM8 RNA transcripts are found in ϳ10% of either DRG or trigeminal ganglion (TG) soma (McKemy et al, 2002;Peier et al, 2002), and the current models for expression come largely from in situ hybridization analyses (Peier et al, 2002;Nealen et al, 2003;Kobayashi et al, 2005). Thus, to more readily identify TRPM8 neurons both in vivo and in vitro, we established a line of transgenic mice, using BAC clone transgenesis, in which cell-specific expression of enhanced GFP is driven by the Trpm8 transcriptional promoter.…”

TRP Channels and Pruritus

“…TRPA1 was originally described as a noxious cold (<17 °C) activated channel expressed by sensory neurons [310,311]. Besides cold, it is also activated by various, mostly pungent and/or irritant compounds such as botanical substances like mustard oil, delta-9-tetrahydrocannabinol, eugenol, gingerol, methyl salicylate, allyl isothiocyanate, cinnamaldehyde, formalin, and nicotine [312][313][314][315].…”