Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat.

1. The pharmacological profile of Spantide, [D-Arg1, D-Trp7,9, Leu11] substance P, as a substance P (SP) antagonist was examined in isolated spinal cords of newborn rats. Potential changes were recorded extracellularly from a lumbar ventral root (L1-L5). Application of SP to the perfusion bath with a brief pressure pulse of 0.05-0.8 s duration produced a dose-dependent depolarization of the ventral root. Spantide in concentrations of 2-16 microM depressed the depolarizing responses of the ventral root to SP in a concentration-dependent manner. The log dose-response curve of SP was shifted to the right in the presence of 16 microM-Spantide by log 5. The responses to neurokinin A (NKA) and bombesin were similarly depressed by 16 microM-Spantide whereas the responses to noradrenaline, gamma-aminobutyric acid (GABA), neurotensin and thyrotrophin-releasing hormone were not affected by 16 microM-Spantide. 2. In an isolated spinal cord-tail preparation of the newborn rat, brief pulse injection of capsaicin into the perfusion solution of the tail induced a depolarizing response in a lumbar ventral root (L3-L5). This response probably represents a nociceptive C fibre reflex. 3. The capsaicin-induced nociceptive reflex was markedly depressed by 16 microM-Spantide and the reflex recovered its original amplitude and shape 30-60 min after removal of Spantide. 4. The capsaicin-induced nociceptive reflex was depressed by morphine (2 microM) and dynorphin (1-13) (0.2 microM), and these effects were reversed by 1 microM-naloxone. 5. In an isolated spinal cord preparation of the newborn rat, stimulation of a dorsal root with single or double shocks induced depolarizing responses of slow time course in both ipsilateral and contralateral ventral roots of the same segment. These slow depolarizing responses were also depressed by 16 microM-Spantide. In contrast the monosynaptic reflex was not affected by 16 microM-Spantide. 6. The present results suggest that SP and NKA are involved as neurotransmitters in the capsaicin-induced nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat.