Contribution of substance P and neurokinin A to the differential injury-induced thermal and mechanical responsiveness of lamina I and V neurons.
In a previous report, we compared the properties of lamina V neurons of the spinal cord dorsal horn in wild-type mice and in mice with a deletion of the preprotachykinin-A (PPT-A) gene, which encodes substance P (SP) and neurokinin A (NKA). The mutant mice had pronounced deficits in the response to thermal stimulation, both before and after mustard oil induced sensitization. Here, we extended our analysis to the properties of lamina I neurons and also examined responsiveness to mechanical stimulation. Consistent with the properties of lamina V neurons, in the PPT-A mutant mice we found significantly reduced responses of lamina I neurons to noxious thermal stimulation, and mustard oil sensitization of these neurons to heat was lost. In contrast, not only were the responses of lamina I neurons to noxious mechanical stimulation unchanged in the mutant mice, but in neither the wild-type nor the mutant mice could sensitization be induced. However, mustard oil profoundly sensitized lamina V neurons to mechanical stimulation in both wild-type and mutant mice. We conclude that SP and/or NKA are required for the transmission of noxious thermal stimulation by lamina I and V neurons, both before and after tissue injury. The persistence of mechanical sensitization of lamina V neurons in the mutant mice further shows that mustard oil induces mechanical and thermal sensitization through different mechanisms. Finally, we conclude that lamina I sensitization to mechanical stimulation is not required for this form of injury-increased responsiveness of lamina V neurons.
Mazarío
Javier
J
Laboratorio de Función Sensitivomotora, Hospital Nacional de Parapléjicos, 45071 Toledo, Spain. jmazario@sescam.jccm.es
Basbaum
Allan I
AI
D000818:Animals; D005260:Female; D006358:Hot Temperature; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015288:Neurokinin A / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D020671:Posterior Horn Cells / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology; D013373:Substance P / Q000502:physiology*
D013373:Substance P; D015288:Neurokinin A