5-HT receptors involved in opioid-activated descending inhibition of spinal withdrawal reflexes in the decerebrated rabbit

Abstract

The role of 5-HT(1B/1D), 5-HT(2) and 5-HT(3) receptors in mediating descending inhibition of spinal reflexes activated by application of fentanyl to the fourth ventricle has been studied in rabbits decerebrated under N(2)O/isoflurane anaesthesia. In the control state, intraventricular fentanyl (3-30 microg kg(-1)) depressed, to an equal extent, short- and long-latency reflexes in the medial gastrocnemius muscle nerve evoked by electrical stimulation of all sural nerve afferents. Inhibition of reflexes resulted from a decreased base line excitability in the reflex pathway accompanied by a reduction in the rate of temporal summation of responses. Fentanyl-induced suppression of short- and long-latency reflexes was significantly reduced after intrathecal administration of the selective 5-HT(2)-receptor antagonist ICI 170,809 (300 microg). The same dose of the selective 5-HT(1B/1D) blocker GR 127,935 reduced inhibition from intraventricular fentanyl only for long-latency reflexes (i.e. those parts of the response for which the afferent drive is provided mainly by Adelta and C-fibre afferents). The 5-HT(3) antagonist tropisetron (also 300 microg intrathecal) did not significantly alter the descending inhibition of reflexes evoked by fentanyl. Both GR 127,935 and tropisetron reduced temporal summation of reflexes per se, effects that were reversed by intraventricular fentanyl. These data suggest that the descending pathway(s) activated by intraventricular fentanyl liberate 5-HT in the spinal cord to inhibit withdrawal reflexes by acting at 5-HT(2) and 5-HT(1B/1D), but not 5-HT(3) receptors. 5-HT(1B/1D), and to a lesser extent 5-HT(3) receptors also appear to have a role in modulating temporal summation of reflexes evoked by repetitive stimuli.

Systemic morphine produce antinociception mediated by spinal 5‐HT7, but not 5‐HT1A and 5‐HT2 receptors in the spinal cord

“…Seven families of 5‐HT receptors (5‐HT 1–7 ) have been identified, and all of them appear to present in the spinal cord (Millan, 2002). In previous studies, it has been reported that a variety of nonselective 5‐HT receptor antagonist have been shown to reduce the antinociceptive effects of systemic or supraspinal applied opioids (Liu et al , 2002; Nemmani and Mogil, 2003; Lo et al , 2004). In the present study, the finding that spinal selective blockade of 5‐HT 7 receptors by SB‐269970 completely inhibits the antinociceptive effect of systemic morphine suggests that an important contribution of the spinal 5‐HT 7 receptors.…”

Noxious radiant heat evokes bi-component nociceptive withdrawal reflexes in spinal cord injured humans—A clinical tool to study neuroplastic changes of spinal neural circuits

“…Thus, laser-evoked nocifensive reflexes assessed with the presented stimulation paradigm may represent a promising yet unique assessment to evaluate nociceptive processing after human SCI. Such a technique may, for instance, be suitable to specifically investigate the involvement of A-delta fibers and C-fibers in clinical studies, e.g., targeting novel drug therapies or spinal maladaptive neuroplastic changes ( Clarke et al, 2002 ; Lo et al, 2004 ). To verify the assumption of inversely related spasticity and neuropathic pain, a further step would be to initiate targeted, ideally translational, research efforts to explicitly evaluate the excitation level of the nervous system and the structural lesion pattern of the spinal cord in the light of central neuropathic pain presentation.…”