Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury.
The neuropeptide galanin has been identified as a potential neurotransmitter/neuromodulator within the central nervous system. In the present study, the role of endogenous galanin in nociceptive processing in the nervous system has been analysed by using mice carrying a targeted mutation in the galanin gene. Supporting this, the effect of chronic administration of exogenous galanin on nociceptive sensory inputs has been assayed in adult rats. In the absence of peripheral nerve injury, the sensitivity to threshold noxious stimuli is significantly higher in galanin mutant mice than wild-type controls. Following peripheral nerve injury, in conditions under which endogenous galanin levels are elevated, spontaneous and evoked neuropathic pain behaviours are compromised in mutant mice. Conversely, chronic intrathecal delivery of exogenous galanin to nerve-intact adult rats is associated with persistent behavioural hypersensitivity, a significant increase in c-fos expression and an increase in PKCgamma immunoreactivity within the spinal cord dorsal horn. The present results demonstrate that a relationship exists between the degree of nerve injury-induced galanin expression and the degree of behavioural hypersensitivity, and show that galanin may play a role in nociceptive processing in the spinal cord, with interrelated inhibitory and excitatory effects.
Kerr
B J
BJ
Sensory Functions Research Group, Center for Neuroscience Research, GKT School of Biomedical Sciences, Kings College London, London SE1 1UL, UK.
Cafferty
W B
WB
Gupta
Y K
YK
Bacon
A
A
Wynick
D
D
McMahon
S B
SB
Thompson
S W
SW
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019004:Galanin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology; D007150:Immunohistochemistry; D007278:Injections, Spinal; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D007527:Isoenzymes; D016760:Proto-Oncogene Proteins c-fos; D019004:Galanin; D011493:Protein Kinase C