D-Arg1, D-Trp7,9, Leu11-substance P (spantide) does not antagonize substance P-induced hyperexcitability of the nociceptive flexion withdrawal reflex in the rat.

The effect of D-Arg1, D-Trp7,9, Leu11-substance P (SP) (spantide), a putative SP antagonist, on SP-induced facilitation of the flexion reflex was examined. The drugs were injected intrathecally (i.t.) in decerebrate, spinalized, unanaesthetized rats. Substance P (10 ng) caused an increase in reflex magnitude for about 5 min. Spantide (10 ng and 100 ng) also caused a facilitation of the reflex that was similar to SP. Spantide (10 ng) plus SP (10 ng) also had a similar excitatory effect. One microgram of spantide totally blocked the flexion reflex, which could not be reversed by SP, L-glutamate, L-aspartate or naloxone. It is concluded that spantide does not have an antagonistic effect on SP-induced changes in spinal reflex excitability. Some of the effects of i.t. spantide observed in behavioural studies may be due to a non-specific spinal motor block. It is suggested that the flexion reflex in the decerebrate, spinalized rat is a useful physiological model in studies of the effects of algesic and analgesic drugs at spinal level.