Differential contribution of TRPV1 to thermal responses and tissue injury-induced sensitization of dorsal horn neurons in laminae I and V in the mouse.
Our previous recordings from dorsal root ganglion and spinal lamina V neurons from TRPV1-mutant mice showed dramatic decreases in responses to temperatures near the activation threshold of this channel (43-49 degrees C). Somewhat unexpectedly, we only observed behavioral deficits in these mice at higher temperatures (50-58 degrees C). In the present study, we tested the hypothesis that the noxious heat-evoked pain behavior that persists in TRPV1-mutant mice reflects residual responsiveness of neurons in the superficial, but not deep, dorsal horn. To this end, we performed in vivo extracellular recordings of spinal nociresponsive neurons in laminae I and V in wild type (WT) and TRPV1 mutant mice. Neurons in WT and mutant mice from both laminae did not differ in their spontaneous activity or evoked responses to mechanical or cold stimuli. By contrast, most lamina I neurons from mutant mice responded to noxious heat with significantly higher thresholds than in WT mice. In contrast, lamina V neurons from mutant mice were virtually unresponsive to noxious heat before and after topical mustard oil-induced tissue injury. Interestingly, lamina I neurons in mutant mice displayed thermal sensitization following tissue injury, comparable in magnitude, but of shorter duration, than in WT mice. We conclude that TRPV1 is necessary for noxious heat-evoked responses of lamina V neurons, both before and after tissue injury. It is also an essential contributor to the normal activation threshold of lamina I neurons to noxious heat and for the full duration of thermal sensitization of lamina I neurons following injury. Finally, our results suggest that the processing of noxious thermal messages by neurons in lamina I involves convergent inputs from a heterogeneous population of primary afferent thermal nociceptors.
Eckert
W A
WA
Department of Anatomy, W.M. Keck Foundation Center for Integrative Neuroscience, University of California at San Francisco, San Francisco, CA 94143, USA. weckert@inspirepharm.com
Julius
D
D
Basbaum
A I
AI
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin / Q000494:pharmacology; D003080:Cold Temperature; D004594:Electrophysiology; D006358:Hot Temperature; D051379:Mice; D018345:Mice, Knockout; D009149:Mustard Plant; D010146:Pain / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D017288:Pain Threshold; D010812:Physical Stimulation; D010938:Plant Oils / Q000494:pharmacology*; D020671:Posterior Horn Cells; D012867:Skin / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
D018712:Analgesics, Non-Narcotic; D010938:Plant Oils; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin; C027793:mustard oil