An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of diabetic neuropathic pain

被引:34
作者
Lynch, JL [1 ]
Jarvis, MF [1 ]
Kowaluk, EA [1 ]
机构
[1] Abbott Labs, Div Pharmaceut Prod, Dept 47C, Abbott Pk, IL 60064 USA
关键词
allodynia; adenosine kinase; adenosine; Streptozotocin; diabetes; pain;
D O I
10.1016/S0014-2999(98)00840-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The present study was conducted to characterize the development of tactile allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate the antinociceptive effects of systemically administered morphine and the adenosine kinase inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) in this model. Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels were determined 3-4 weeks later. Diabetic (blood glucose levels greater than or equal to 250 mg/dl) and vehicle-injected rats were examined weekly for the development of tactile allodynia by measuring the threshold for hind paw withdrawal using von Frey hairs. Withdrawal thresholds were reduced to 6.8 +/- 0.6 g (mean +/- S.E.M.) in approximately one-third of streptazotocin-treated rats 7 weeks after streptozotocin treatment as compared to control thresholds (13.2 +/- 0.1 g), and this allodynia persisted for at least an additional 7 weeks. In additional experiments, morphine sulfate (5-21 mu mol/kg, i.p.) produced dose-dependent antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The adenosine kinase inhibitor, 5'd-5TT (2.5 and 5 mu mol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 mu mol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 mu mol/kg, i.p.) significantly diminished the anti-allodynic effects of morphine and 5'd-5IT, respectively. The present study demonstrates that the potent and selective adenosine kinase inhibitor, 5'd-5IT, is equally effective as morphine in blocking tactile allodynia in this model. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:141 / 146
页数:6
相关论文
共 42 条
  • [1] MECHANICAL HYPERALGESIA IN STREPTOZOTOCIN-DIABETIC RATS
    AHLGREN, SC
    LEVINE, JD
    [J]. NEUROSCIENCE, 1993, 52 (04) : 1049 - 1055
  • [2] AKUNNE HC, 1987, PSYCHOPHARMACOLOGY, V93, P167
  • [3] LACK OF ANALGESIC EFFECT OF OPIOIDS ON NEUROPATHIC AND IDIOPATHIC FORMS OF PAIN
    ARNER, S
    MEYERSON, BA
    [J]. PAIN, 1988, 33 (01) : 11 - 23
  • [4] BRITTON DR, 1996, ABSTR SOC NEUROSCI, V22, P1568
  • [5] DIABETIC NEUROPATHY
    BROWN, MJ
    ASBURY, AK
    [J]. ANNALS OF NEUROLOGY, 1984, 15 (01) : 2 - 12
  • [6] Tactile allodynia and formalin hyperalgesia in streptozotocin-diabetic rats: Effects of insulin, aldose reductase inhibition and lidocaine
    Calcutt, NA
    Jorge, MC
    Yaksh, TL
    Chaplan, SR
    [J]. PAIN, 1996, 68 (2-3) : 293 - 299
  • [7] DIFFERENT EFFECTS OF 2 ALDOSE REDUCTASE INHIBITORS ON NOCICEPTION AND PROSTAGLANDIN-E
    CALCUTT, NA
    LI, L
    YAKSH, TL
    MALMBERG, AB
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1995, 285 (02) : 189 - 197
  • [8] Spinal pharmacology of tactile allodynia in diabetic rats
    Calcutt, NA
    Chaplan, SR
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1997, 122 (07) : 1478 - 1482
  • [9] 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
  • [10] PREVENTION AND TREATMENT OF THE COMPLICATIONS OF DIABETES-MELLITUS
    CLARK, CM
    LEE, DA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (18) : 1210 - 1217