Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception. The use of intrathecal (IT) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether IT neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (IT) and peripheral (intraarticular; IA) neostigmine in a rat inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was assessed over 28 h using a modified Hargreaves box and von Frey hairs, respectively. IT neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 mu g, 24-28 h: 9.4 mu g) and mechanical analgesia (ED50 0-4 h: 3.5 mu g, 24-28 h: 4.3 mu g) IT atropine reversed analgesia by TT neostigmine. IA neostigmine also resulted in an IA atropine reversible dose-dependent increase of thermal analgesia, although it did not exceed 60% of a maximal possible analgesic effect with the largest applied dose (ED50 0-4 h: 76.2 mu g, 24-28 h: 140.1 mu g). Partial suppression of mechanical hyperalgesia was observed after IA neostigmine. We conclude that centrally administered neostigmine modulates thermal and mechanical antinociception in this animal model of inflammatory pain. These data suggest a peripheral site of muscarinic antinociception. Implications: This animal study shows that administration of the acetylcholinesterase-inhibitor neostigmine results in enhanced levels of the endogenous neurotransmitter acetylcholine, which seems to act as one of a group of analgesia-modulating compounds at central and peripheral sites in inflammatory pain.
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UNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USA
Buerkle, H
Yaksh, TL
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UNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USA
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UNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZILUNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZIL
DUARTE, IDG
LORENZETTI, BB
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UNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZILUNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZIL
LORENZETTI, BB
FERREIRA, SH
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UNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZILUNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZIL
机构:
UNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USA
Buerkle, H
Yaksh, TL
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h-index: 0
机构:
UNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, ANESTHESIA RES LAB, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USA
机构:
UNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZILUNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZIL
DUARTE, IDG
LORENZETTI, BB
论文数: 0引用数: 0
h-index: 0
机构:
UNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZILUNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZIL
LORENZETTI, BB
FERREIRA, SH
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h-index: 0
机构:
UNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZILUNIV SAO PAULO, FAC MED RIBEIRAO PRETO, DEPT PHARMACOL, BR-14049 RIBEIRAO PRETO, BRAZIL