Inflammation-induced up-regulation of neurokinin 1 receptors in rat glabrous skin.

Peripheral inflammation sensitizes primary afferent fibers causing lowered thresholds and increased responses to noxious input. One mechanism for sensitization might be increased expression of receptors whose activation results in nociceptor activity. Accordingly, the present study demonstrates that 15.6% of unmyelinated primary afferent axons in rat glabrous skin express the neurokinin 1 (NK1) receptor. At 48 h following hindpaw inflammation with complete Freund's adjuvant, the proportion of unmyelinated axons expressing NK1 receptors significantly increases to 23.6%. This implies a considerable upregulation of NK1 receptor synthesis in the dorsal root ganglia with subsequent transport to peripheral nociceptive terminals. Antagonizing peripheral NK1 receptors locally would be effective in reducing inflammatory pain by reducing neural transduction in NK1-expressing nociceptors as well as lessening the inflammatory vascular effects of peripheral substance P.