TRPV1 unlike TRPV2 is restricted to a subset of mechanically insensitive cutaneous nociceptors responding to heat.
In the present study, a murine ex vivo somatosensory system preparation was used to determine the response characteristics of cutaneous sensory neurons staining positively for TRPV1 or TRPV2. TRPV1 immunostaining was found exclusively (11/11) in a specific set of mechanically insensitive unmyelinated (C) nociceptors that responded to heating of their receptive fields. No cutaneous C-fibers that responded to both mechanical and heat stimuli stained positively for TRPV1 (0/62). The relationship between TRPV2 and heat transduction characteristics was not as clear, as few unmyelinated or myelinated fibers that responded to heat contained TRPV2. TRPV2 was found most frequently in mechanically sensitive myelinated fibers, including both low threshold and high threshold mechanoreceptors (nociceptors). Although TRPV2 was found in only 1 of 6 myelinated polymodal nociceptors, it was found in a majority (10/16) of myelinated mechanical nociceptors. Thus, whereas the in vivo role of TRPV1 as a heat-sensitive channel in cutaneous sensory neurons is clearly defined, the role of TRPV2 in cutaneous neurons remains unknown. These results also suggest that TRPV1 may be essential for heat transduction in a specific subset of mechanically insensitive cutaneous nociceptors and that this subset may constitute a discrete heat input pathway for inflammation-induced thermal pain.


CONCLUSIONS
The distinct subset of murine cutaneous nociceptors containing TRPV1 has many attributes in common with mechanically insensitive C-fibers in humans that are believed to play a role in pathological pain states. Therefore, these murine fibers provide a clinically relevant animal model for further study of this group of cutaneous nociceptors.
Lawson
Jeffrey J
JJ
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
McIlwrath
Sabrina L
SL
Woodbury
C Jeffery
CJ
Davis
Brian M
BM
Koerber
H Richard
HR
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008465:Mechanoreceptors / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D009924:Organ Culture Techniques; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012867:Skin / Q000294:innervation*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D013697:Thermosensing / Q000502:physiology*
D015220:Calcium Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C485717:Trpv2 protein, mouse; D015740:Calcitonin Gene-Related Peptide