engleski

Aninociceptive activity of botulinum toxin type A

Objective Over the last 20 years botulinum toxin type A (BTX-A) has been used for treating a variety of disorders characterized by increased muscle contraction and recently few clinical observations on several patients indicated that it might be useful in neuropathic pain. However, up to now preclinical nociceptive action of BTX-A has been investigated in only few studies. Here we overview the efficacy of BTX-A in different models of pain in rat, from published sttudies and some new studies from our laboratory. Method All experiments were performed in rats. After dose-response and time-course experiments performed with BTX-A using formalin and carrageenan to provoke acute pain associated with inflammation, the effectiveness of BTX-A on chronic neuropathic pain was tested. Peripheral neuropathy was evoked by partial sciatic nerve transection. Animals which developed neuropathic pain showed increased sensitivity to thermal and mechanical stimuli and were included in further investigation and treated with BTX-A. Pain of muscular origin was studied using model of double injections of low pH saline in gastrocnemius muscle. Results 1. Pre-treatment with BTX-A 5 U/kg significantly reduced or completely abolished enhanced sensitivity to mechanical and thermal stimuli provoked with peripheral carrageenan or capsaicin injections. This reduction was significant when BTX-A was applied 6 days before the induction of pain and inflammation while the toxin was ineffective when applied 24 h before the challenge. In the dose-response experiment, the lowest effective dose was 3.5 U/kg, but apparently the effect was not dose-dependent. In contrast to the antinociceptive effect, BTX-A 5 U/kg did not affect the carrageenan-induced paw-edema. 2. A peripheral application of botulinum toxin type A (7 U/kg) has significantly reduced thermal and mechanical hypersensitivity in rats with the partial sciatic nerve transection as a classical model of surgical neuropathy. 3. BTX-A was effective in muscular pain induced injection of low pH saline (Bach-Rojecky at al. this Congress) Conclusion The results obtained in our laboratory, together with data other investigations (Cui et al.Pain 2004 ; 107:125 and Chuang et al. J Urol 2004 ; 172:1529) clearly demonstrate antinociceptive activity of small doses of BTX-A in experimental animals. Since single application of BTX-A in rat produces antinociceptive effect lasting 12- 15 days or more the potential significance for pain pharmacology is more than clear. However, (a) five days delay in the onset of antinociceptive activity of peripherally applied BTX-A, (b) its effectiveness in different models of experimental pain with assumed different mechanism of antinociceptive action, as well as (c) its ineffectiveness in reducing carrageenan induced paw-edema, observed in our study, indicate that the antinociceptive action of BTX-A might be much more complex than suggested inhibition of transmitter release in the periphery.

botulinum toxin type A; pain

Riječ je o poster konferenciji (poster i predavanje, takve konferencije organizirane su na poziv tj. uz recenziju)