Galanin and spinal pain mechanisms: past, present, and future

Since the discovery of galanin in 1983, one of the most frequently suggested physiological function for this peptide is pain modulation at the level of the spinal cord. This notion, initially based on the preferential distribution of galanin in dorsal spinal cord, has been supported by results from a large number of morphological, molecular, and functional studies. It is generally agreed that spinally applied galanin produces a biphasic, dose-dependent effect on spinal nociception through activation of GalR1 (inhibitory) or GalR2 (excitatory) receptors. Galanin also appears to have an endogenous inhibitory role, particularly after peripheral nerve injury when the synthesis of galanin is increased in sensory neurons. In recent years, small molecule ligands of galanin receptors have been developed, which may lead to the development of analgesic drugs, which affects the galanin system at the spinal cord level.