The antinociceptive effect of anterior pretectal nucleus stimulation is mediated by distinct neurotransmitter mechanisms in descending pain pathways.

Abstract

Electrical stimulation of the anterior pretectal nucleus (APtN) activates two descending pain inhibitory pathways. One of these pathways relays in the ipsilateral lateral paragigantocellular nucleus (LPGi), whereas the other pathway relays in the contralateral pedunculopontine tegmental nucleus (PPTg). Antinociceptive effect of APtN stimulation has been seen in various pain models in the rodents. Similarly, LPGi or PPTg stimulation results in higher pain thresholds. Descending antinociceptive pathways activated by electrical APtN stimulation have been elucidated, but the underlying neurotransmitter mechanisms involved have not been clarified yet. This study investigates the role that endogenous signaling plays in the ipsilateral LPGi or contralateral PPTg after the APtN is stimulated in the tail-flick test. First, we submitted rats to excitotoxic injection of N-methyl-d-aspartate (NMDA) into the contralateral PPTg. Then, we examined whether blockage of NMDA (AP-7), serotonergic (methysergide), or opioid (naloxone) receptors in the ipsilateral LPGi is required for APtN stimulation-evoked analgesia (SEA). Likewise, we examined the effects of antagonists of NMDA, serotonergic, or cholinergic nicotinic (mecamylamine) receptors on the contralateral PPTg in ipsilateral LPGi-lesioned rats. Our results confirmed that APtN stimulation activates two pain inhibitory pathways and showed that endogenous opioid signaling in the ipsilateral LPGi appears to be necessary for APtN SEA and for endogenous NMDA, serotoninergic, and nicotinergic signaling in the contralateral PPTg.

• Authors: Karina Genaro, Débora Fabris, Wiliam A Prado
• Journal: Brain research bulletin (Brain Res Bull) Vol. 146 Pg. 164-170 (03 2019) ISSN: 1873-2747 [Electronic] United States
• PMID: 30634015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Analgesics, Opioid
• Narcotic Antagonists
• Neurotransmitter Agents
• Naloxone
• N-Methylaspartate
• Methysergide

Topics

• Analgesia (methods)
• Analgesics, Opioid
• Animals
• Electric Stimulation
• Male
• Methysergide
• N-Methylaspartate (pharmacology)
• Naloxone
• Narcotic Antagonists (pharmacology)
• Neurotransmitter Agents (metabolism, pharmacology)
• Nociceptors (metabolism)
• Pain (metabolism, physiopathology)
• Pain Management (methods)
• Pain Measurement (drug effects)
• Pedunculopontine Tegmental Nucleus (drug effects, metabolism)
• Pretectal Region (drug effects, metabolism)
• Rats
• Rats, Wistar