Morphine increases acetylcholine release in the trigeminal nuclear complex

Zhenghong Zhu, Heather R. Bowman, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Study Objectives: 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. Design: 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. Measurements and 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.

Original languageEnglish (US)
Pages (from-to)1629-1637
Number of pages9
JournalSleep
Volume31
Issue number12
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Fingerprint

Trigeminal Nuclei
Morphine
Acetylcholine
Opioid Analgesics
Naloxone
Bethanechol
Bicuculline
Microdialysis
Tetrodotoxin
Sodium Channel Blockers
Ala(2)-MePhe(4)-Gly(5)-enkephalin
GABA-A Receptor Antagonists
Muscarinic Agonists
Cholinergic Neurons
Narcotic Antagonists
Isoflurane
Mastication
Jaw
Action Potentials
Brain Stem

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Physiology (medical)

Cite this

Morphine increases acetylcholine release in the trigeminal nuclear complex. / Zhu, Zhenghong; Bowman, Heather R.; Baghdoyan, Helen; Lydic, Ralph.

In: Sleep, Vol. 31, No. 12, 01.12.2008, p. 1629-1637.

Research output: Contribution to journalArticle

Zhu, Zhenghong ; Bowman, Heather R. ; Baghdoyan, Helen ; Lydic, Ralph. / Morphine increases acetylcholine release in the trigeminal nuclear complex. In: Sleep. 2008 ; Vol. 31, No. 12. pp. 1629-1637.
@article{7bb5a3fccc394638a27fc867bd6610ef,
title = "Morphine increases acetylcholine release in the trigeminal nuclear complex",
abstract = "Study Objectives: 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. Design: 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. Measurements and 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.",
author = "Zhenghong Zhu and Bowman, {Heather R.} and Helen Baghdoyan and Ralph Lydic",
year = "2008",
month = "12",
day = "1",
doi = "10.1093/sleep/31.12.1629",
language = "English (US)",
volume = "31",
pages = "1629--1637",
journal = "Sleep",
issn = "0161-8105",
publisher = "American Academy of Sleep Medicine",
number = "12",

}

TY - JOUR

T1 - Morphine increases acetylcholine release in the trigeminal nuclear complex

AU - Zhu, Zhenghong

AU - Bowman, Heather R.

AU - Baghdoyan, Helen

AU - Lydic, Ralph

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Study Objectives: 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. Design: 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. Measurements and 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.

AB - Study Objectives: 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. Design: 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. Measurements and 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.

UR - http://www.scopus.com/inward/record.url?scp=57349102262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57349102262&partnerID=8YFLogxK

U2 - 10.1093/sleep/31.12.1629

DO - 10.1093/sleep/31.12.1629

M3 - Article

VL - 31

SP - 1629

EP - 1637

JO - Sleep

JF - Sleep

SN - 0161-8105

IS - 12

ER -