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Antinociceptive Effect of Botulinum Toxin Type A in Experiemtal Diabetic Neuropathy

OBJECTIVE: In alloxan induced diabetes in rats we investigated the possibility that BTX-A has antinociceptive ativity in diabetic neuropathy. BACKGROUND: Recently we found that peripheral application of botulinum toxin type A significantly reduced thermal and mechanical hypersensitivity in rats with the partial sciatic nerve transection as a classical model of surgical neuropathy (Bach-Rojecky at al. J. Neural Transm 2005 ; 112: 215-219). DESIGN/METHODS: Adult male Wistar rats (250-300 g) were made diabetic by a single subcutaneous (s.c.) injection of alloxan (200 mg/kg b.w.) Control animals were injected s.c. with the same volume of saline. After 5 days only animals with a tail-vein blood-glucose concentration of above 15 mmol/l (colorensic PAP method) were considered diabetic and included in the study. Paw-pressure tests were first performed 3 weeks following alloxan or saline injection in order to asses thermal and mechanical nociceptive sensitivity. Only the animals with significantly different mechanical thresholds compared to control group were considered neuropathic (hyperalgesic) and were than subjected to BTX-A or saline treatment. Mechanical sensitivity was tested once per week. Formalin test (5% formalin injection into the hind-paw) was performed only once. RESULTS: On day 5 after BTX-A 5 and 7 U/kg treatment significant antinociceptive effect was observed i.e. diminished number of flinches and shakes of the formalin-injected paw. The lowest used dose (3 U/kg) was ineffective. Mechanical sensitivity to pressure was tested on day 5, 7, 10, 15, 22 and 27 following toxin injection. The antinociceptive effect of BTX-A 5 and 7 U/kg was significant compared to untreated diabetic controls til the day 15 and than started to decrease. CONCLUSIONS/RELEVANCE: To our knowledge this is the first demonstration that a single peripheral injection of BTX might have a long-lasting antinociceptive effect in diabetic neuropathy.

Ppain; neurotransmitters; diabetic neuropathy; botulinum toxin

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