N- and C-terminal fragments of substance P: spinal effects in the rat tail flick test

Evidence exists to suggest that within the CNS, substance P may be enzymatically cleaved into fragments which may mediate some of the effects of substance P. As we have previously reported on the spinal effects of substance P, the present study examines the effects of selected substance P fragments on reaction time in the tail flick test. Peptides were administered via a chronically implanted intrathecal catheter to the L5 vertebral level in the rat. Administration of 6.5 nmoles of SP(1-7) produced a transient decrease in reaction time at 1 min after injection with a return to above control values by 5 min. Similar administration of SP(7-11) produced a smaller decrease in reaction time at 6 min which lasted until 16 min. Administration of 6.5 nmoles of SP(1-9), SP(8-11) and of CSF were without effect. As the effects of SP(1-7) on reaction time resembled those of similar administration of substance P in the earlier experiments, these results suggest that this fragment may be the active component involved in facilitating the tail flick reflex. Substance P may be degraded to the active fragment prior to receptor activation or alternatively, substance P and SP(1-7) may act on the same receptor.