Spinal endogenous acetylcholine contributes to the analgesic effect of systemic morphine in rats.
BACKGROUND
Systemic morphine is known to cause increased release of acetyicholine in the spinal cord. Intrathecal injection of the cholinergic receptor agonists or acetyicholinesterase inhibitors produces antinociception in both animals and humans. In the present study, we explored the functional importance of spinal endogenous acetylcholine in the analgesic action produced by intravenous morphine.


METHODS
Rats were implanted with intravenous and intrathecal catheters. The antinociceptive effect of morphine was determined by the paw-withdrawal latency in response to a radiant heat stimulus after intrathecal treatment with atropine (a muscarinic receptor antagonist), mecamylamine (a nicotinic receptor antagonist), or cholinergic neurotoxins (ethylcholine mustard aziridinium ion [AF64A] and hemicholinium-3).


RESULTS
Intravenous injection of 2.5 mg/kg morphine increased significantly the paw-withdrawal latency. Intrathecal pretreatment with 30 microg atropine (n = 7) or 50 microg mecamylamine (n = 6) both attenuated significantly the antinociceptive effect of morphine. The inhibitory effect of atropine on the effect of morphine was greater than that of mecamylanilne. Furthermore, the antinociceptive effect of morphine was significantly reduced in rats pretreated with intrathecal AF64A (n = 7) or hemicholinium-3 (n = 6) to inhibit the high-affinity choline transporter and acetylcholine synthesis. We found that intrathecal AF64A reduced significantly the [3H]hemicholinium-3 binding sites but did not affect its affinity in the dorsal spinal cord.


CONCLUSIONS
The data in the current study indicate that spinal endogenous acetylcholine plays an important role in mediating the analgesic effect of systemic morphine through both muscarinic and nicotinic receptors.
Chen
S R
SR
Department of Anesthesiology, Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
Pan
H L
HL
D000109:Acetylcholine / Q000502:physiology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001388:Aziridines / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D026901:Membrane Transport Proteins; D009020:Morphine / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology*
D000701:Analgesics, Opioid; D001388:Aziridines; D002352:Carrier Proteins; D018678:Cholinergic Agents; D026901:Membrane Transport Proteins; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; C065637:choline transporter; D006426:Hemicholinium 3; D008464:Mecamylamine; D009020:Morphine; D001285:Atropine; C044894:ethylcholine aziridinium; D002794:Choline; D000109:Acetylcholine