Neurokinin Receptors

Substance P is expressed in a greater percentage of visceral afferent fibers than somatic afferent fibers (164). This suggests that tachykinins may contribute to viscerosensory processing. Inflammation of the colon or bladder increases neurokinin-1 (NK1) receptor expression in the gut wall, colonic afferent fibers, and spinal dorsal horn neurons (165,166) and concomi-tantly decreases substance P expression in primary afferents (11). NK1 receptor internalization in spinal dorsal horn neurons increases following CRD of the normal and inflamed colon (167). However, parasitic gastric inflammation decreases NK1 receptor expression in the spinal cord, and increases substance P expression in dorsal root ganglia (168).

Consistent with an upregulation of NK1 receptor activity, spinal administration of NK1 receptor antagonists generally attenuate the visceromotor response evoked from distention of the inflamed colon (169-171) or in acutely stressed rats (172) and visceral hyperalgesia is attenuated in NK1 receptor knockout mice (173). Likewise, spinally administered NK3 receptor antagonists attenuate the visceromotor response (171,174).

In contrast to a decidedly spinal site of action, peripherally, but not spinally administered NK2 receptor antagonists attenuate the visceromotor response to CRD (40,171,175).

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