Morphine increases acetylcholine release in the trigeminal nuclear complex.
OBJECTIVE
The trigeminal nuclear complex (V) contains cholinergic neurons and includes the principal sensory trigeminal nucleus (PSTN) which receives sensory input from the face and jaw, and the trigeminal motor nucleus (MoV) which innervates the muscles of mastication. Pain associated with pathologies of V is often managed with opioids but no studies have characterized the effect of opioids on acetylcholine (ACh) release in PSTN and MoV. Opioids can increase or decrease ACh release in brainstem nuclei. Therefore, the present experiments tested the 2-tailed hypothesis that microdialysis delivery of opioids to the PSTN and MoV significantly alters ACh release.


METHODS
Using a within-subjects design and isoflurane-anesthetized Wistar rats (n=53), ACh release in PSTN during microdialysis with Ringer's solution (control) was compared to ACh release during dialysis delivery of the sodium channel blocker tetrodotoxin, muscarinic agonist bethanechol, opioid agonist morphine, mu opioid agonist DAMGO, antagonists for mu (naloxone) and kappa (nor-binaltorphimine; nor-BNI) opioid receptors, and GABAA antagonist bicuculline.


RESULTS
Tetrodotoxin decreased ACh, confirming action potential-dependent ACh release. Bethanechol and morphine caused a concentration-dependent increase in PSTN ACh release. The morphine-induced increase in ACh release was blocked by nor-BNI but not by naloxone. Bicuculline delivered to the PSTN also increased ACh release. ACh release in the MoV was increased by morphine, and this increase was not blocked by naloxone or nor-BNI.


CONCLUSIONS
These data comprise the first direct measures of ACh release in PSTN and MoV and suggest synaptic disinhibition as one possible mechanism by which morphine increases ACh release in the trigeminal nuclei.
Zhu
Zhenghong
Z
Department ofAnesthesiology, University of Michigan, Ann Arbor, MI 48109-5615, USA.
Bowman
Heather R
HR
Baghdoyan
Helen A
HA
Lydic
Ralph
R
D000109:Acetylcholine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014278:Trigeminal Nuclei / Q000187:drug effects*
D000701:Analgesics, Opioid; D018756:GABA Antagonists; D018721:Muscarinic Agonists; D026941:Sodium Channel Blockers; D018723:Bethanechol; D013779:Tetrodotoxin; D009020:Morphine; D000109:Acetylcholine; D001640:Bicuculline