neurokinin-a and Neuritis

The excitatory neurotransmitter glutamate coexists with the peptide known as substance P in primary afferents that respond to painful stimulation. Because blockers of glutamate receptors reliably reduce pain behaviour, it is assumed that 'pain' messages are mediated by glutamate action on dorsal horn neurons. The contribution of substance P, however, is still unclear. We have now disrupted the mouse preprotachykinin A gene (PPT-A), which encodes substance P and a related tachykinin, neurokinin A. We find that although the behavioural response to mildly painful stimuli is intact in these mice, the response to moderate to intense pain is significantly reduced. Neurogenic inflammation, which results from peripheral release of substance P and neurokinin A, is almost absent in the mutant mice. We conclude that the release of tachykinins from primary afferent pain-sensing receptors (nociceptors) is required to produce moderate to intense pain.

Topics: Animals; Cloning, Molecular; Female; Gene Targeting; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Neuritis; Neurokinin A; Nociceptors; Pain; Protein Precursors; Receptors, Neurokinin-1; Sensory Thresholds; Sequence Deletion; Stimulation, Chemical; Substance P; Tachykinins

Antidromic electrical stimulation of sensory nerves produces vascular hyperpermeability, plasma protein extravasation and oedema. The initial phase of this inflammatory reaction is induced by the release of the neuropeptides CGRP, SP and NKA; the later phase is induced by mast cells. In previous investigations we were able to show that the facial nerve of the rat contains CGRP, SP and NKA as well as mast cells. The same mechanism--increased vascular permeability--plasma extravasation--oedema--is thought to be part of the pathogenesis of Bell's palsy. Hence, we tried to produce neurogenic inflammations in the facial nerves of six adult Wistar rats. To assess plasma extravasation we used Evans blue, a dye which binds to serum albumin, according to the method described by Brokaw and White (1992). Having cut the facial nerve distal of the stylomastoid foramen we induced a neurogenic inflammation by the application of an electrical stimulus to the distal part of the nerve. In comparison to the contralateral, non-stimulated side, we recognized that the inflammatory reactions were limited to the area of the skin innervated by the posterior auricular nerve. So far, we can transfer this "neurogenic inflammation model" the well-known relationship between nerves and inflammatory reactions to this limited area innervated by the facial nerve.

Topics: Animals; Calcitonin Gene-Related Peptide; Capillary Permeability; Electric Stimulation; Extravasation of Diagnostic and Therapeutic Materials; Facial Nerve; Neuritis; Neurokinin A; Rats; Rats, Wistar; Substance P; Vasodilation