Fragments of galanin message-associated peptide (GMAP) modulate the spinal flexor reflex in rat

We have previously reported that galanin message-associated peptide (GMAP), a fragment of galanin precursor protein, is present in dorsal root ganglion cells and upon intrathecal (i.t.) administration influences the spinal nociceptive flexor reflex in a complex manner in the rat. GMAP elicited a moderate facilitation of the flexor reflex, but when administered prior to conditioning stimulation of C-afferents, it dose dependently blocked spinal cord hyperexcitability. The present study examined the effects of four fragments of GMAP-(1-60), GMAP-(1-12), GMAP-(10-24), GMAP-(25-44) and GMAP-(37-60), on the flexor reflex and compared them with the effects of the complete peptide sequence. All four GMAP fragments facilitated the flexor reflex. However, this effect was dose-dependent only for GMAP-(1-12) and the effect of GMAP-(1-12) was stronger than GMAP-(1-60). In contrast, only GMAP-(25-44) dose dependently blocked the facilitation of the flexor reflex induced by the C-fiber conditioning stimulation. The potency of the blocking effect of GMAP-(25-44) was one order of magnitude lower than that of GMAP-(1-60). The results indicated that two fragments of GMAP are pharmacologically active and produce effects which are similar to the full sequence. It is possible that the complex effect of GMAP may be mediated by different subtypes of GMAP receptors which recognize different portions of the GMAP sequence.