The
neuropeptide galanin is present at high levels within the dorsal root ganglia (DRG) and spinal cord during development and after peripheral nerve damage in the adult. This pattern of expression suggests that it may play a role in the adaptive response of the peripheral nervous system (PNS) to injury. Several experimental paradigms have demonstrated that
galanin modulates
pain transmission, particularly after nerve injury. In our laboratory we have used a transgenic approach to further elucidate the functions of
galanin within the somatosensory system. We have generated mice which over-express
galanin (either inducibly after nerve injury, or constitutively), and knock-out (KO) mice, in which
galanin is absent in all cells, throughout development and in the adult. Analysis of the nociceptive behaviour of the
galanin over-expressing animals, before and after nerve injury, supports the view that
galanin is an inhibitory
neuromodulator of spinal cord transmission. In apparent contradiction to these findings,
galanin KO animals fail to develop
allodynia and
hyperalgesia after nerve injury. However, further studies have shown that
galanin is critical for the developmental survival of a subset of small diameter, unmyelinated sensory neurons that are likely to be nociceptors. This finding may well explain the lack of
neuropathic pain-like behaviour after injury in the KO animals. Furthermore, the developmental survival role played by
galanin is recapitulated in the adult where the
peptide is required for optimal neuronal regeneration after injury, and in the hippocampus where it plays a neuroprotective role after excitotoxic injury.