engleski

Bilateral antinociceptive effect of botulinum toxin type A in a rat model of „mirror“ pain involves spinal GABA

Background and aims: According to recent observations botulinum toxin type A (BTX-A) alleviates different types of pain by acting within central nervous system, but the mechanism of its central action is poorly understood. Previously we reported the bilateral antinociceptive effect of BTX-A in carrageenan induced bilateral muscle pain. Here we investigated the effects of selective GABA antagonist bicuculline on BTX-A’s bilateral antinociceptive effect. Methods: Male Wistar rats were injected into right gastrocnemius muscle with 100 μL of 3% carrageenan or saline. Animals which developed bilateral secondary mechanical allodynia (tested with von Frey filaments) were divided into groups (6 animals per group): saline or BTX-A (5 U/kg) (intraplantar, into the right hind paw) ; saline or BTX-A + bicuculline (1 µg/ 10 µL, intrathecal) ; saline or BTX-A + bicuculline (1 µg/ 10 µL, into cisterna magna). BTX-A was injected 5 days and bicuculline 30 min before nociceptive testing. Results: Unilaterally injected BTX-A decreased mechanical hypersensitivity not only on ipsilateral (p<0.001), but on the contralateral side as well (p<0.001). Intrathecal, low dose of bicuculline abolished the bilateral antinociceptive effect in BTX-A treated animals (p<0.001), while the same dose applied into cisterna magna had no effect on BTX-A’s antinociceptive action. Bicuculline alone had no effect on carrageenan induced bilateral allodynia. Conclusions: Unilaterally injected BTX-A has bilateral antinociceptive effect in carrageenan induced bilateral pain that can be prevented with GABA antagonist bicuculline. This indicates the involvement of central GABA-ergic system in bilateral antinociceptive effect of BTX-A, most probably at spinal level.

Botulinum toxin A; Mirror pain; GABA-A receptor; bicuculline

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