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This Article Full Text Full Text (PDF) All Versions of this Article: 97/4/2651    most recent 00840.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Rau, K. K. Articles by Cooper, B. Y. Search for Related Content PubMed PubMed Citation Articles by Rau, K. K. Articles by Cooper, B. Y.

Heat Sensitization in Skin and Muscle Nociceptors Expressing Distinct Combinations of TRPV1 and TRPV2 Protein

¹Department of Oral Surgery and Diagnostic Sciences, Division of Neuroscience, J. Hillis Miller Health Center, University of Florida College of Dentistry and McKnight Brain Institute, Gainesville; and ²Department of Physiological Sciences, College of Veterinary Medicine and University of Florida, McKnight Brain Institute, JHMHC, University of Florida, Gainesville, Florida

Submitted 10 August 2006; accepted in final form 1 February 2007

Recordings were made from small and medium diameter dorsal root ganglia (DRG) neurons that expressed transient receptor potential (TRP) proteins. Physiologically characterized skin nociceptors expressed either TRPV1 (type 2) or TRPV2 (type 4) in isolation. Other nociceptors co-expressed both TRP proteins and innervated deep tissue sites (gastrocnemius muscle, distal colon; type 5, type 8) and skin (type 8). Subpopulations of myelinated (type 8) and unmyelinated (type 5) nociceptors co-expressed both TRPs. Cells that expressed TRPV1 were excellent transducers of intense heat. Proportional inward currents were obtained from a threshold of 46.5 to 56°C. In contrast, cells expressing TRPV2 alone (52°C threshold) did not reliably transduce the intensity of thermal events. Studies were undertaken to assess the capacity of skin and deep nociceptors to exhibit sensitization to repeated intense thermal stimuli [heat-heat sensitization (HHS)]. Only nociceptors that expressed TRPV2, alone or in combination with TRPV1, exhibited HHS. HHS was shown to be Ca²⁺ dependent in either case. Intracellular Ca²⁺ dependent pathways to HHS varied with the pattern of TRP protein expression. Cells co-expressing both TRPs modulated heat reactivity through serine/threonine phosphorylation or PLA₂-dependent pathways. Cells expressing only TRPV2 may have relied on tyrosine kinases for HHS. We conclude that heat sensitization in deep and superficial capsaicin and capsaicin-insensitive C and A nociceptors varies with the distribution of TRPV1 and TRPV2 proteins. The expression pattern of these proteins are specific to subclasses of physiologically identified C and A fiber nociceptors with highly restricted tissue targets.