• Taylor BK and McCarson KE (2004). Neurokinin-1 receptor gene expression in the mouse dorsal horn increases with neuropathic pain. J Pain. 5: 71-6. Peripheral nerve injury is associated with hyperesthesia and increased neurokinin-1 receptor (NK-1) expression in the dorsal horn of the spinal cord. To test the hypothesis that NK-1 gene expression underlies these responses, we used solution hybridization-nuclease protection assays to quantify NK-1 mRNA levels in dorsal quadrants of the mouse lumbar dorsal horn. Partial sciatic nerve ligation was associated with mechanical allodynia, thermal hyperalgesia, and an increase in NK-1 mRNA on the ipsilateral, but not contralateral, side. Regression analysis showed that NK-1 mRNA was significantly correlated with thermal paw withdrawal latency but not mechanical threshold. Our results support the idea that substance P is an important mediator of thermal hypersensitivity in the setting of nerve injury and suggest that increased NK-1 receptor transcription precedes increased NK-1 receptor density, ultimately leading to behavioral hypersensitivity to peripheral thermal stimulation. PERSPECTIVE: The therapeutic efficacy of NK-1 receptor antagonists is unclear. The current data suggest that peripheral nerve injury increases the expression of substance P (NK-1) receptors in the spinal cord dorsal horn; this is correlated with heat hypersensitivity. The analgesic effects of NK-1 antagonists might become apparent if tested against heat-evoked pain in nerve injury patients.