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Investigation into atropine-induced antinociception
C Ghelardini1, P Malmberg-Aiello, A Giotti
1Department of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy.
British Journal of Pharmacology
|September 1, 1990
Summary
Low doses of atropine (acetylcholine receptor antagonist) provide pain relief (analgesia) in rodents by acting on the central nervous system. Higher doses, however, cause increased pain sensitivity (hyperalgesia).
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- The nociceptive system processes pain signals.
- Cholinergic neurotransmission plays a role in pain modulation.
- Atropine, an anticholinergic agent, has complex effects on pain perception.
Purpose of the Study:
- To investigate the dose-dependent effects of atropine on pain perception in rodents.
- To determine the mechanism of action and receptor subtypes involved in atropine's antinociceptive effects.
- To explore the potential of atropine as an analgesic agent.
Main Methods:
- Pain was assessed in mice and rats using hot-plate, writhing, and tail-flick tests.
- Atropine was administered at various doses, and its effects were compared with other drugs.
- In vitro studies on guinea-pig ileum contractions were conducted to assess atropine's effects on cholinergic transmission.
Main Results:
- Atropine exhibited a biphasic effect: analgesia at low doses (1-100 µg/kg) and hyperalgesia at high doses (5 mg/kg).
- Atropine's antinociception was blocked by muscarinic receptor antagonists (pirenzepine, dicyclomine) and hemicholinium-3, indicating a central nervous system mechanism.
- In vitro, low concentrations of atropine enhanced cholinergic contractions, while high concentrations inhibited them, suggesting presynaptic muscarinic autoreceptor blockade.
Conclusions:
- Low-dose atropine amplifies cholinergic transmission via presynaptic muscarinic autoreceptor blockade, leading to analgesia.
- M1 muscarinic receptor subtypes are implicated in mediating atropine's analgesic effects.
- Atropine-induced analgesia occurs without motor impairment, differentiating it from other cholinergic analgesics like oxotremorine.