Neurokinin-1 receptor gene expression in the mouse dorsal horn increases with neuropathic pain.
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.


CONCLUSIONS
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.
Taylor
Bradley K
BK
Deparment of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA 70018, USA. taylorb@tulane.edu
McCarson
Kenneth E
KE
D000818:Animals; D015870:Gene Expression; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009437:Neuralgia / Q000503:physiopathology*; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D012584:Sciatic Nerve / Q000293:injuries; D014110:Touch
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1