TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hypersensitivity after muscle inflammation.
Inflammatory thermal hyperalgesia is principally mediated through transient receptor potential vanilloid 1 (TRPV1) channels, as demonstrated by prior studies using models of cutaneous inflammation. Muscle pain is significantly different from cutaneous pain, and the involvement of TRPV1 in hyperalgesia induced by muscle inflammation is unknown. We tested whether TRPV1 contributes to the development of mechanical and heat hypersensitivity of the paw in TRPV1(-/-) mice after muscle inflammation. Because TRPV1(-/-) mice lack TRPV1 at the site of inflammation (muscle) and at the testing site (paw), we do not know whether TRPV1 is important as a mediator of nociceptor sensitization in the muscle or as a heat sensor in the paw. Using recombinant herpesviruses, we reexpressed TRPV1 in TRPV1(-/-) mice in primary afferents innervating skin, muscle, or both to determine which sites were important for the behavioral deficits. Responses to repeated application of noxious mechanical stimuli to the hind paw were enhanced in TRPV1(-/-) mice; this was restored by reexpression of TRPV1 into skin. Withdrawal latencies to noxious heat were increased in TRPV1(-/-) mice; normal latencies were restored by reexpression of TRPV1 in both skin and muscle. Heat hypersensitivity induced by muscle inflammation did not develop in TRPV1(-/-) mice; mechanical hypersensitivity was similar between TRPV1(-/-) and TRPV1(+/+) mice. Heat hypersensitivity induced by muscle inflammation was restored by reexpression of TRPV1 into both muscle and skin of TRPV1(-/-) mice. These results suggest that TRPV1 serves as both a mediator of nociceptor sensitization at the site of inflammation and as a heat sensor at the paw.
Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA College of Pharmacy, Roseman University of Health Sciences-Utah Campus, South Jordan, UT 84095, USA Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Roxanne Y
RY
Walder
Rajan
R
Radhakrishnan
Lipin
L
Loo
Lynn A
LA
Rasmussen
Durga P
DP
Mohapatra
Steven P
SP
Wilson
Kathleen A
KA
Sluka
D000818:Animals; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009220:Myositis / Q000150:complications / Q000503:physiopathology*; D012684:Sensory Thresholds / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D013697:Thermosensing / Q000502:physiology*; D014110:Touch
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse