Endogenous galanin potentiates spinal nociceptive processing following inflammation.
We have undertaken a series of experiments using galanin null mutant mice to better define the role of endogenous galanin in spinal excitability following inflammation and in response to centrally sensitizing stimuli. We have employed a behavioural paradigm, the formalin test, as a model of tonic nociception in both galanin knock-out (gal-/-) and wild-type (gal+/+) mice. In this model, we find that gal-/- mice are markedly hypo-responsive, especially in the second phase response. Additionally, we have examined the thermal hyperalgesia which develops following peripheral injection of carrageenan into the plantar surface of one hindpaw. In this inflammatory paradigm, thermal hyperalgesia is markedly attenuated in gal-/- mice. These behavioural findings suggest that endogenous galanin contributes to nociceptive processing. We have tested this hypothesis further by employing an electrophysiological measure of spinal excitability, the flexor withdrawal reflex in gal-/- and gal+/+ mice. We found no differences in acute reflex responses to single stimuli at C-fibre strength or in the time course and magnitude of wind-up induced by a short conditioning train between non-inflamed gal+/+ and gal-/- mice. However, the long-lasting post-conditioning enhancement of reflex excitability was only seen in gal+/+ mice. Moreover, following carrageenan inflammation, there was a marked increase in spinal nociceptive reflex excitability in the inflamed gal+/+ mice, but this enhanced excitability was absent in gal-/- animals. These findings illustrate that endogenous galanin is necessary for the full expression of central sensitization, and as such, plays a critical role in the development of hyperalgesia following peripheral tissue injury.
Kerr
Bradley J
BJ
Centre for Neuroscience Research, Guy's, King's and St. Thomas' School of Biomedical Sciences, Kings College, London Bridge, London SE1 1UL, UK Department of Medicine, University of Bristol, Bristol, UK.
Gupta
Yuri
Y
Pope
Robert
R
Thompson
Stephen W N
SWN
Wynick
David
D
McMahon
Stephen B
SB
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D019004:Galanin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009187:Myelitis / Q000235:genetics / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods*; D020671:Posterior Horn Cells / Q000503:physiopathology; D012018:Reflex / Q000235:genetics
D019004:Galanin