Endogenous galanin potentiates spinal nociceptive processing following inflammation

We have undertaken a series of experiments using galanin null mutant mice t o better define the role of endogenous galanin in spinal excitability follo wing inflammation and in response to centrally sensitizing stimuli. We have employed a behavioural paradigm, the formalin test, as a model of tonic no ciception in both galanin knock-out (gal-/-) and wild-type (gal+/+) mice. I n this model, we find that gal-/- mice are markedly hypo-responsive, especi ally in the second phase response. Additionally, we have examined the therm al hyperalgesia which develops following peripheral injection of carrageena n into the plantar surface of one hindpaw. In this inflammatory paradigm, t hermal hyperalgesia is markedly attenuated in gal-/- mice. These behavioura l findings suggest that endogenous galanin contributes to nociceptive proce ssing. We have tested this hypothesis further by employing an electrophysio logical measure of spinal excitability, the flexor withdrawal reflex in gal -/- and gal+/+ mice. We found no differences in acute reflex responses to s ingle stimuli at C-fibre strength or in the time course and magnitude of wi nd-up induced by a short conditioning train between non-inflamed gal+/+ and gal-/- mice. However, the Iona-lasting post-conditioning enhancement of re flex excitability was only seen in gal+/+ mice. Moreover, following carrage enan inflammation, there was a marked increase in spinal nociceptive reflex excitability in the inflamed gal+/+ mice, but this enhanced excitability w as absent in gal-/- animals. These findings illustrate that endogenous gala nin is necessary for the full expression of central sensitization, and as s uch, plays a critical role in the development of hyperalgesia following per ipheral tissue injury. Copyright (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.