Inhibition Of Tail-flick Reflex Research Articles

5-hydroxytryptamine 1A (5-HT 1A) but not 5-HT 3 receptor is involved in mediating the nucleus submedius 5-HT-evoked antinociception in the rat

Our previous studies have indicated that the thalamic nucleus submedius (Sm) is involved in modulation of nociception as part of an ascending component of an endogenous analgesic system consisting of spinal cord-Sm-ventrolateral orbital cortex (VLO)-periaqueductal gray (PAG)-spinal cord loop. Microinjection of 5-hydroxytryptamine (5-HT) into Sm produces antinociception and this effect is blocked by 5-HT 2 receptor antagonist. The aim of the present study was to examine whether the 5-HT 1 and 5-HT 3 receptors were also involved in the Sm 5-HT-evoked antinociception. Nociception was assessed in lightly anesthetized rats with radiant-heat-evoked tail flick (TF). 5-HT 1A and 5-HT 3 receptor antagonists were microinjected into the Sm alone or in combination with a microinjection of 5-HT into the same Sm site. 5-HT 1A receptor antagonist p-MPPI (0.87 nmol) facilitated the TF reflex; a lower dose (0.43 nmol) of p-MPPI significantly attenuated the Sm 5-HT-evoked inhibition of TF reflex. Microinjection of the 5-HT 3 receptor antagonist LY-278,584 (12 nmol) had no effect either on the TF reflex or on the Sm 5-HT-evoked inhibition. These results suggest that 5-HT 1A receptor but not 5-HT 3 receptor is involved in mediating the 5-HT-evoked antinociception. Possible mechanisms of Sm 5-HT-induced descending antinociception are discussed.

Inhibitory effects of 5-hydroxytryptamine microinjection into thalamic nucleus submedius on rat tail flick reflex are mediated by 5-HT 2 receptors

Our previous findings indicated that electrical or chemical activation of the thalamic nucleus submedius (Sm) produced significant antinociceptive effects and that these effect were blocked by lesion or depression of the ventrolateral orbital cortex (VLO) or the periaqueductal gray (PAG) suggesting a role of the Sm in modulation of nociception. To further investigate the neurotransmitter mechanism involved in this nociceptive modulatory pathway, we tested the effects of microinjection of 5-hydroxytryptamine (5-HT, 50 mM, 0.5 μl) into Sm on the tail flick (TF) reflex. The results show that a unilateral microinjection of 5-HT into Sm significantly depresses the TF reflex; and that this effect is repeatable and dose-dependent. Furthermore, microinjection of 5-HT 2 receptor antagonist cyproheptadine (CPT, 0.3 mM, 0.5 μl) into the same Sm site reverses this 5-HT-evoked inhibition of TF reflex. These results suggest that 5-HT application to the Sm may activate Sm neurons through the 5-HT 2 receptors leading to activation of the brainstem descending inhibitory system via the VLO and depression of the nociceptive information at the spinal level.

Role of the deep mesencephalic nucleus in the antinociception induced by stimulation of the anterior pretectal nucleus in rats

The present study showed that the inhibitory effect on the tail-flick reflex (TF) of stimulating the deep mesencephalic nucleus (DpMe) was very similar to that produced by stimulation of the anterior pretectal nucleus (APtN). An electrolytic lesion of the ipsilateral DpMe greatly reduced the inhibitory effect of APtN stimulation on the TF. Furthermore, activating the neuronal cell bodies in DpMe but not the fibers of passage by microinjection of l-glutamate into this area was also shown to elicit inhibition of TF. On the other hand, inhibiting the neuronal cells in DpMe by microinjection of γ-aminobutyric acid produced a marked reduction in the APtN-induced inhibition of TF, which was comparable to that produced by DpMe lesions. It is suggested that the APtN-induced antinociception is, at least in part, mediated via a relay through the DpMe.

Effect of spinal norepinephrine depletion on descending inhibition of the tail flick reflex from the locus coeruleus and lateral reticular nucleus in the rat

The lateral reticular nucleus (LRN) and locus coeruleus-subcoeruleus (LC/SC), brainstem structures which overlap the A 1 and A 6 noradrenergic nuclei respectively, have been implicated in descending modulation of spinal nociceptive transmission. The present studies were designed to examine the role of norepinephrine (NE) in the mediation of inhibition of the nociceptive tail flick reflex produced by focal electrical stimulation in the LRN and LC/SC. Spinal NE was depleted by intrathecal administration of 6-hydroxydopamine (6-OHDA; 20 μg) and the threshold electrical stimulation in the LRN and the LC/SC necessary to inhibit the tail flick reflex in lightly pentobarbital-anesthetized rats was determined 9 and 14 days later. Despite a significant depletion ( 85%) of lumbar spinal cord NE content, there was no significant change in the tail flick inhibitory stimulation thresholds in the LRN or LC/SC. NE depletion did, however, potentiate the elevation in the inhibitory stimulation threshold in the LRN produced by intrathecal administration of theα 2-adrenoceptor antagonist, yohimbine, suggesting that upregulation of spinal adrenoceptors had occurred following 6-OHDA treatment. Adrenoceptor up-regulation was examined quantitatively by (1) characterizing the dose-dependent antinociceptive potency of the selectiveα 2-adrenoceptor agonist clonidine 3, 7, 10, and 14 days following 6-OHDA administration, and (2) analysis of [ 3H]rauwolscine binding to lumbar spinal cord 9 days following administration of the neurotoxin. The development of supersensitivity, defined as the leftward parallel shift of the dose-response curves for clonidine administered intrathecally, corresponded to the time course of NE depletion following 6-OHDA treatment on the days tested. Binding of [ 3H]rauwolscine to lumbar spinal cord revealed an elevation in the estimated B max without a change in the estimated K d of the high affinity binding component 9 days following 6-OHDA administration. This study demonstrates that spinal adrenoceptor denervation supersensitivity develops rapidly following intrathecal administration of 6-OHDA and compensates for the selective destruction of spinal noradrenergic nerve terminals. Thus, the absence of effect of NE depletion on the tail flick inhibitory stimulation threshold in the LRN and the LC/SC does not argue against the hypothesis that spinopetal NE-containing neurons in these brainstem loci are involved in modulation of spinal nociceptive transmission.