STUDY OF THE SENSITIVITY OF THE DIABETES-INDUCED PAIN MODEL IN RATS TO A RANGE OF ANALGESICS

The streptozocin-induced diabetic rat has been put forward as a model of chronic pain with signs of hyperalgesia and allodynia that may refl ect signs observed in diabetic humans. The aim of this work was to ass ess, in streptozocin-induced diabetic rats, the pharmacological activi ty to several analgesic drugs known to be effective (clomipramine, ami triptyline, desipramine, clonidine, lidocaine), ineffective (aspirin), or with a doubtful effectiveness (morphine) in human painful diabetic neuropathy. The animals were submitted to a mechanical pain test (paw pressure) and the ability of the drugs to reverse diabetes-induced hy peralgesia was tested. The tested antidepressants (0.125-8 mg/kg, i.v. ) were slightly effective in diabetic rats; amitriptyline and clomipra mine induced a weak effect, whereas desipramine was more active, sugge sting noradrenergic specificity. This was confirmed by the effectivene ss of clonidine (50, 100, 150 mu g/kg, s.c.). Lidocaine (1-9 mg/kg, i. v.) had prolonged efficacy on mechanical hyperalgesia. Aspirin (100 mg /kg, i.v.) was without effect and morphine (0.5-4 mg/kg, i.v.) induced a dose-dependent antinociceptive effect but at doses twice as high as those used in normal rats. These results demonstrate the high pharmac ological predictivity of this model of painful diabetes and suggest th at in this pathological condition, among the drugs acting on monoamine rgic transmission, noradrenergic drugs seem the most active.