Stimulation-produced analgesia from the occipital or retrosplenial cortex of rats involves serotonergic and opioid mechanisms in the anterior pretectal nucleus.

UNLABELLED: The electrical stimulation of the occipital (OC) or retrosplenial (RSC) cortex produces antinociception in the rat tail-flick test. These cortices send inputs to the anterior pretectal nucleus (APtN) which is implicated in antinociception and nociception. At least muscarinic cholinergic, opioid, and serotonergic mechanisms in the APtN are involved in stimulation-produced antinociception (SPA) from the nucleus. In this study, the injection of 2% lidocaine (.25 µL) or methysergide (40 and 80 ng/.25 µL) into the APtN reduced the duration but did not change the intensity of SPA from the OC, whereas both duration and intensity of SPA from the RSC were significantly reduced in rats treated with lidocaine or naloxone (10 and 50 ng/.25 µL), injected into the APtN. Naloxone or methysegide injected into the APtN was ineffective against SPA from the OC or RSC, respectively. Atropine (100 ng/.25 µL) injected into the APtN was ineffective against SPA from either the OC or RSC. We conclude that the APtN acts as an intermediary for separate descending pain inhibitory pathways activated from the OC and RSC, utilizing at least serotonin and endogenous opioid as mediators in the nucleus. PERSPECTIVE: Stimulation-induced antinociception from the retrosplenial or occipital cortex in the rat tail-flick test depends on the activation of separate descending pain inhibitory pathways that utilize the APtN as a relay station.

Antinociceptive effect of stimulating the occipital or retrosplenial cortex in rats.

UNLABELLED: A role for the occipital or retrosplenial cortex in nociceptive processing has not been demonstrated yet, but connections from these cortices to brain structures involved in descending pain-inhibitory mechanisms were already demonstrated. This study demonstrated that the electrical stimulation of the occipital or retrosplenial cortex produces antinociception in the rat tail-flick and formalin tests. Bilateral lesions of the dorsolateral funiculus abolished the effect of cortical stimulation in the tail-flick test. Injection of glutamate into the same targets was also antinociceptive in the tail-flick test. No rats stimulated in the occipital or retrosplenial cortex showed any change in motor performance on the Rota-rod test, or had epileptiform changes in the EEG recording during or up to 3 hours after stimulation. The antinociception induced by occipital cortex stimulation persisted after neural block of the retrosplenial cortex. The effect of retrosplenial cortex stimulation also persisted after neural block of the occipital cortex. We conclude that stimulation of the occipital or retrosplenial cortex in rats leads to antinociception activating distinct descending pain-inhibitory mechanisms, and this is unlikely to result from a reduced motor performance or a postictal phenomenon. PERSPECTIVE: This study presents evidence that stimulation of the retrosplenial or occipital cortex produces antinociception in rat models of acute pain. These findings enhance our understanding of the role of the cerebral cortex in control of pain.

Serotonin receptors are involved in the spinal mediation of descending facilitation of surgical incision-induced increase of Fos-like immunoreactivity in rats.

BACKGROUND: Descending pronociceptive pathways may be implicated in states of persistent pain. Paw skin incision is a well-established postoperative pain model that causes behavioral nociceptive responses and enhanced excitability of spinal dorsal horn neurons. The number of spinal c-Fos positive neurons of rats treated intrathecally with serotonin, noradrenaline or acetylcholine antagonists where evaluated to study the descending pathways activated by a surgical paw incision. RESULTS: The number of c-Fos positive neurons in laminae I/II ipsilateral, lamina V bilateral to the incised paw, and in lamina X significantly increased after the incision. These changes: remained unchanged in phenoxybenzamine-treated rats; were increased in the contralateral lamina V of atropine-treated rats; were inhibited in the ipsilateral lamina I/II by 5-HT1/2B/2C (methysergide), 5-HT2A (ketanserin) or 5-HT1/2A/2C/5/6/7 (methiothepin) receptors antagonists, in the ipsilateral lamina V by methysergide or methiothepin, in the contralateral lamina V by all the serotonergic antagonists and in the lamina X by LY 278,584, ketanserin or methiothepin. CONCLUSIONS: We conclude: (1) muscarinic cholinergic mechanisms reduce incision-induced response of spinal neurons inputs from the contralateral paw; (2) 5-HT1/2A/2C/3 receptors-mediate mechanisms increase the activity of descending pathways that facilitates the response of spinal neurons to noxious inputs from the contralateral paw; (3) 5-HT1/2A/2C and 5-HT1/2C receptors increases the descending facilitation mechanisms induced by incision in the ipsilateral paw; (4) 5-HT2A/3 receptors contribute to descending pronociceptive pathways conveyed by lamina X spinal neurons; (5) alpha-adrenergic receptors are unlikely to participate in the incision-induced facilitation of the spinal neurons.

Muscarinic and alpha(1)-adrenergic mechanisms contribute to the spinal mediation of stimulation-induced antinociception from the pedunculopontine tegmental nucleus in the rat.

The effects of intraperitoneal (i.p.) or intrathecal (i.t.) injection of antagonists of acetylcholine, noradrenaline, serotonin, dopamine, opioids and GABA on stimulation-produced antinociception (SPA) from the pedunculopontine tegmental nucleus (PPTg) of rats were studied using the tail-flick test. The electrical stimulation of the PPTg produced a strong and long-lasting increase in tail-flick latency. The intensity and duration of the effect were significantly reduced in rats pretreated with i.p. or i.t. atropine (a non-selective muscarinic cholinergic antagonist), or i.t. phenoxybenzamine or WB 4101 (non-selective and selective alpha(1)-adrenergic antagonists, respectively). Intraperitoneal phenoxybenzamine, i.p. or i.t. methysergide or naloxone (non-selective serotonin and opioid antagonists, respectively), or i.t. idazoxan (a selective alpha(2)-adrenergic antagonist) only reduced the duration of the effect. The duration of SPA from the PPTg was increased by i.t. phaclofen (a GABA(B) antagonist). The effect from the nucleus was not altered following i.t. bicuculline (a GABA(A) antagonist), or i.p. or i.t. mecamylamine, propranolol or haloperidol (non-selective nicotinic cholinergic, beta-adrenergic and dopaminergic antagonists, respectively). Thus, SPA from the PPTg involves the spinal activation of muscarinic and alpha(1)-adrenergic but not nicotinic cholinergic, beta-adrenergic and dopaminergic mechanisms. Serotonergic, endogenous opioid and alpha(2)-adrenergic mechanisms are involved in the duration but not in the intensity of the effect.