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POSTOPERATIVE ANALGESIA INDUCED BY INTRATHECAL NEOSTIGMINE OR BETHANECHOL IN RATS
Author(s) -
Prado WA,
Dias TB
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05128.x
Subject(s) - neostigmine , bethanechol , intrathecal , anesthesia , medicine , receptor , muscarinic acetylcholine receptor
SUMMARY1 Cholinergic agonists and acetylcholinesterase inhibitors, such as neostigmine, produce a muscarinic receptor‐mediated antinociception in several animal species that depends on activation of spinal cholinergic neurons. However, neostigmine causes antinociception in sheep only in the early, and not late, postoperative period. 2 In the present study, a model of postoperative pain was used to determine the antinociceptive effects of bethanechol (a muscarinic agonist) and neostigmine administered intrathecally 2, 24 or 48 h after a plantar incision in a rat hind paw. Changes in the threshold to punctate mechanical stimuli were evaluated using an automated electronic von Frey apparatus. 3 Mechanical hyperalgesia was obtained following plantar incision, the effect being stronger during the immediate (2 h) than the late post‐surgical period. Bethanechol (15–90 µg/5 µL) or neostigmine (1–3 µg/5 µL) reduced incision‐induced mechanical hyperalgesia, the effects of both drugs being more intense during the immediate (2 h) than the late post‐surgical period. 4 The ED 50 for bethanechol injected at 2, 24 and 48 h was 5.6, 51.9 and 82.5 µg/5 µL, respectively. The corresponding ED 50 for neostigmine was 1.62, 3.02 and 3.8 µg/5 µL, respectively. 5 The decline in the antinociceptive potency of neostigmine with postoperative time is interpreted as resulting from a reduction in pain‐induced activation of acetylcholine‐releasing descending pathways. However, the similar behaviour of bethanechol in the same model points to an additional mechanism involving intrinsic changes in spinal muscarinic receptors.