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The Journal of Neuroscience, January 24, 2007, 27(4):762-770; doi:10.1523/JNEUROSCI.2992-06.2007

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Behavioral/Systems/Cognitive
Contribution of Substance P and Neurokinin A to the Differential Injury-Induced Thermal and Mechanical Responsiveness of Lamina I and V Neurons

Javier Mazarío¹ and Allan I. Basbaum²

¹Laboratorio de Función Sensitivomotora, Hospital Nacional de Parapléjicos, 45071 Toledo, Spain, and ²Departments of Anatomy and Physiology and W. M. Keck Center for Integrative Neuroscience, University of California San Francisco, San Francisco, California 94158

Correspondence should be addressed to Javier Mazarío, Laboratorio de Función Sensitivomotora, Hospital Nacional de Parapléjicos, 45071 Toledo, Spain. Email: jmazario{at}sescam.jccm.es

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.

Key words: pain; tachykinins; mustard oil; knock-out; dorsal horn; allodynia

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Received July 14, 2006; revised Dec. 13, 2006; accepted Dec. 13, 2006.

Correspondence should be addressed to Javier Mazarío, Laboratorio de Función Sensitivomotora, Hospital Nacional de Parapléjicos, 45071 Toledo, Spain. Email: jmazario{at}sescam.jccm.es

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