Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor neostigmine in the rat inflamed knee joint model

被引:56
作者
Buerkle, H [1 ]
Boschin, M [1 ]
Marcus, MAE [1 ]
Brodner, G [1 ]
Wüsten, R [1 ]
Van Aken, H [1 ]
机构
[1] Univ Munster, Klin & Poliklin Anasthesiol & Operat Intens Med, D-48129 Munster, Germany
关键词
D O I
10.1097/00000539-199805000-00023
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
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.
引用
收藏
页码:1027 / 1032
页数:6
相关论文
共 22 条
  • [1] Necessity for an animal model of postoperative pain
    Abram, SE
    [J]. ANESTHESIOLOGY, 1997, 86 (05) : 1015 - 1017
  • [2] ANTONIJEVIC I, 1995, J NEUROSCI, V15, P165
  • [3] Comparison of the spinal actions of the mu-opioid remifentanil with alfentanil and morphine in the rat
    Buerkle, H
    Yaksh, TL
    [J]. ANESTHESIOLOGY, 1996, 84 (01) : 94 - 102
  • [4] QUANTITATIVE ASSESSMENT OF TACTILE ALLODYNIA IN THE RAT PAW
    CHAPLAN, SR
    BACH, FW
    POGREL, JW
    CHUNG, JM
    YAKSH, TL
    [J]. JOURNAL OF NEUROSCIENCE METHODS, 1994, 53 (01) : 55 - 63
  • [5] PERIPHERAL ANALGESIA AND ACTIVATION OF THE NITRIC OXIDE-CYCLIC GMP PATHWAY
    DUARTE, IDG
    LORENZETTI, BB
    FERREIRA, SH
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 186 (2-3) : 289 - 293
  • [6] A NEW AND SENSITIVE METHOD FOR MEASURING THERMAL NOCICEPTION IN CUTANEOUS HYPERALGESIA
    HARGREAVES, K
    DUBNER, R
    BROWN, F
    FLORES, C
    JORIS, J
    [J]. PAIN, 1988, 32 (01) : 77 - 88
  • [7] PHASE-I SAFETY ASSESSMENT OF INTRATHECAL NEOSTIGMINE METHYLSULFATE IN HUMANS
    HOOD, DD
    EISENACH, JC
    TUTTLE, R
    [J]. ANESTHESIOLOGY, 1995, 82 (02) : 331 - 343
  • [8] CARDIORESPIRATORY AND SPINAL-CORD BLOOD-FLOW EFFECTS OF INTRATHECAL NEOSTIGMINE METHYLSULFATE, CLONIDINE, AND THEIR COMBINATION IN SHEEP
    HOOD, DD
    EISENACH, JC
    TONG, CY
    TOMMASI, E
    YAKSH, TL
    [J]. ANESTHESIOLOGY, 1995, 82 (02) : 428 - 435
  • [9] Dose-response study of intrathecal morphine versus intrathecal neostigmine, their combination, or placebo for postoperative analgesia in patients undergoing anterior and posterior vaginoplasty
    Lauretti, GR
    Reis, MP
    Prado, WA
    Klamt, JG
    [J]. ANESTHESIA AND ANALGESIA, 1996, 82 (06) : 1182 - 1187
  • [10] The effects of intrathecal neostigmine on somatic and visceral pain: Improvement by association with a peripheral anticholinergic
    Lauretti, GR
    Lima, ICPR
    [J]. ANESTHESIA AND ANALGESIA, 1996, 82 (03) : 617 - 620