Reduced spinal cord sensitization to C-fibre stimulation in mice over-expressing galanin

The neuropeptide galanin may have a role in spinal nociception. In this study, we examined the excitability of the flexor reflex and its sensitization by repetitive stimulation of nociceptive C-fibres in anaesthetized mice that over-express galanin. No difference was seen between over-expressing galanin and wild-type mice in the magnitude of the baseline flexor reflex. Repetitive conditioning stimulation of C-fibres (10 stimuli at 1 Hz) produced a gradual increase in reflex magnitude during the conditioning stimulation (wind-up), as well as an increase in spinal reflex excitability after the termination of the stimulus train (central sensitization) in wild-type mice. Although the wind-up did not differ between over-expressing galanin and wild-type mice, the magnitude of central sensitization was significantly reduced in the over-expressing galanin mice (24 +/- 13% peak increase compared with 164 +/- 65% in the wild-type). Intrathecal administration of M35, a galanin receptor antagonist, markedly enhanced central sensitization in over-expressing galanin mice in association with C-fibre conditioning stimulation, while having no effect in wild-type mice. These results provide further electrophysiological evidence for an inhibitory function of galanin in modulation of central sensitization in response to C-fibre stimulation.