Spinal Nociceptive Flexor Reflex Research Articles

PD134308, a selective antagonist of cholecystokinin type B receptor, enhances the analgesic effect of morphine and synergistically interacts with intrathecal galanin to depress spinal nociceptive reflexes.

The effects of systemic PD134308 [0.1-3 mg/kg; an antagonist of the cholecystokinin (CCK) type B receptor], morphine, and intrathecal (i.t.) galanin (GAL) on the excitability of the spinal nociceptive flexor reflex and in the hot plate test were examined in rats. PD134308 caused a weak naloxone-reversible depression of the flexor reflex and a moderate antinociceptive effect in the hot plate test. However, PD134308 significantly potentiated the antinociceptive effect of morphine as well as its depressive effect on the flexor reflex. PD134308 and i.t. GAL synergistically depressed the flexor reflex, an effect that was reversed by naloxone. Finally, the magnitude and duration of the depression of the flexor reflex by morphine were synergistically increased by coadministering PD134308 and GAL i.t. The results demonstrated that a CCK antagonist directed to the central CCK type B receptor potentiates the analgesic effects of opioids and nonopioid drugs at the spinal level, thus supporting the notion that CCK in the central nervous system may be an endogenous, physiological opioid antagonist.

Plasticity of the peptidergic mediation of spinal reflex facilitation after peripheral nerve section in the rat

The effects of the tachykinin antagonist Spantide II ( d-Nic-Lys 1,3-Pal 3, d-Cl 2Phe 5,Asn 6 d-Trp 7,9,Nle 11)-substance P (SP) and the vasoactive intestinal peptide (VIP) antagonist (Ac-Tyr 1, d-Phe 2)-GRF(1–29)-NH 2 on the excitability of the spinal nociceptive flexor reflex to intrathecally (i.t.) applied SP and VIP, respectively, as well as the facilitation evoked by activation of cutaneous C-afferent was examined. Both antagonists blocked the effects of the respective neuropeptides in rats with both intact and sectioned sciatic nerves. Spantide II antagonised C-afferent induced reflex facilitation in rats with intact nerves, but the degree of antagonism declined after axotomy. In contrast, the VIP antagonist did not block C-afferent induced facilitation in rats with intact nerves, but did so after axotomy. The results indicate that the role of tachykinins in mediating C-afferent-induced reflex facilitation is taken over by VIP after axotomy.

The N-terminal 1–16, but not C-terminal 17–29, galanin fragment affects the flexor reflex in rats

The biological activity of two galanin (GAL) fragments, GAL-(1–16) and GAL-(17–29), was tested in vivo by using a spinal nociceptive flexor reflex model in the rat. Intrathecal (i.t.) GAL-(1–16) had a similar biphasic effect on the flexor reflex, with facilitation at lower doses and facilitation followed by depression at higher doses, as the full length peptide GAL-(1–29). GAL-(1–16) also effectively depressed the facilitation of the flexor reflex caused by i.t. substance P (SP) or C-fiber conditioning stimulation (CS) and potentiated the depressive effect of i.t. morphine on the reflex, both actions that have been reported earlier with GAL-(1–29). In contrast, i.t. GAL-(17–29), even at high doses, did not induce changes in the amplitude of the flexor reflex, nor did it interact with the effects of i.t. SP, morphine or C-fiber CS. It is concluded that the N-terminal portion of GAL-(1–29) is critical for the biological activity of the intact peptide in the dorsal horn of the rat spinal cord. The similarity between the effects GAL-(1–16) and GAL-(1–29) indicates that they probably act on the same GAL receptor.