Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury

The neuropeptide galanin has been identified as a potential neurotransmitte r/neuromodulator within the central nervous system. In the present study, t he role of endogenous galanin in nociceptive processing in the nervous syst em has been analysed by using mice carrying a targeted mutation in the gala nin gene. Supporting this, the effect of chronic administration of exogenou s galanin on nociceptive sensory inputs has been assayed in adult rats. In the absence of peripheral nerve injury, the sensitivity to threshold noxiou s stimuli is significantly higher in galanin mutant mice than wild-type con trols. Following peripheral nerve injury, in conditions under which endogen ous galanin levels are elevated, spontaneous and evoked neuropathic pain be haviours are compromised in mutant mice. Conversely, chronic intrathecal de livery of exogenous galanin to nerve-intact adult rats is associated with p ersistent behavioural hypersensitivity, a significant increase in c-fos exp ression and an increase in PKC gamma immunoreactivity within the spinal cor d dorsal horn. The present results demonstrate that a relationship exists b etween 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.