engleski

Long-lasting antinociceptive effect of botulinum toxin type a in experimental diabetic neuropathy: surprising bilateral effect after unilateral injection

Recently we found that peripheral application of botulinum toxin type A (BTX-A) reduces hypersensitivity in rats with the partial sciatic nerve transection as a classical model of neuropathy (Bach-Rojecky et al., J. Neural. Transm. 2005 ; 112: 215-219). In human the most common cause of painful neuropathy is diabetes mellitus. In present experiments in rats with streptozotocin-induced diabetes we investigated the possibility that BTX-A has antinociceptive effect in painful neuropathy. Male Wistar rats (250-300 g) were made diabetic by a single subcutaneous (s.c.) injection of streptozotocin (80 mg/kg b.w.). Animals with a tail-vein blood-glucose concentration of above 15 mmol/l were considered diabetic. Sensitivity to mechanical stimuli was measured bilaterally with the paw-pressure test. Measurements started 3 weeks following streptozotocin or saline injection. Only the animals with mechanical thresholds lower for at least for 25% compared to saline-treated group were considered neuropathic and were than subjected to unilateral peripheral (in the plantar surface of the right hindpaws) BTX-A (3, 5 and 7 U/kg) or saline treatment. Mechanical sensitivity was tested bilaterally on day 1, 5, 15 and 28 following BTX-A injection. Statistical analysis was performed with Newman-Keuls post hoc test. BTX-A 5 and 7 U/kg reduced the mechanical hypersensitivity in diabetic animals compared to the saline-treated diabetic control (109.6&#61617; 3 g for BTX-A vs. 86.2&#61617; 5.1 g for control ; p<0.01). The antinociceptive effect was evident on day 5 and was significant till the day 15. Surprisingly, BTX-A reduced the mechanical hypersensitivity on the contralateral hindpaw too. Single peripheral BTX-A injection has a long-lasting bilateral antinociceptive effect in experimental diabetic neuropathy. Surprisingly, after unilateral injection, antinociceptive effect is achieved bilaterally. This observation questions suggested peripheral mechanism of antinociceptive action of BTX-A. Supported by Croatian Ministry of Education, Science and Sport (Project number:108-1080003-0001 ; to Z. Lackovic), and Deutscher Akademischer Austausch Dienst (DAAD)

botulinum toxin; pain; nociception

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