Possible analgesic effect of vigabatrin in animal experimental chronic neuropathic pain

Abstract

-Since anticonvulsants have been used for treating neuralgias, an interest has arisen to experimentally test vigabatrin for its gabaergic mechanism of action. For this, 41 Wistar rats were used, and in 25 of them a constrictive sciatic neuropathy was induced (Bennet & Xie model). For testing pain symptoms, spontaneous (scratching) and evoked behaviors to noxious (46 o C) and non-noxious (40 o C) thermal stimuli were quantified. Moreover, a comparative pharmacological study of vigabatrin with other analgesic anticonvulsant drugs was also performed. The results showed a possible dose-dependent analgesic effect of vigabatrin (gamma-vinyl-GABA) on experimental neuropathic pain, as shown by the significant (p<0.05) decreasing effect of vigabatrin on scratching and by its significant (p<0.05) increasing effect on the latency of the right hindpaw withdrawal of the animals to noxious thermal stimulus. This was corroborated by similar findings with analgesic anticonvulsants (carbamazepine, phenytoin and valproic acid). This possible and not yet described analgesic effect of vigabatrin seems not to be opioid mediated.KEY WORDS: vigabatrin, experimental, neuropathic pain, scratching behavior, thermal tests, Wistar rats, analgesia. Possível efeito analgésico da vigabatrina na dor neuropática crônica experimental animalRESUMO -O uso de anticonvulsivantes no tratamento de neuralgias despertou um interesse em testar novas drogas anticonvulsivantes, e dentre essas a vigabatrina por possuir mecanismo de ação gabaérgico. Para isso, foram usados 41 ratos Wistar e em 25 deles induziu-se neuropatia ciática constritiva (modelo de Bennett & Xie). Para testar sintomas de dor, foram quantificados comportamentos espontâneos (coçar-se) e evocados, por meio de estímulos térmicos nocivos (46 o C) e não-nocivos (40 o C). Além disso, realizou-se estudo comparativo da vigabatrina com outros anticonvulsivantes analgésicos. Os resultados mostraram um possível efeito analgésico, dose-dependente, de vigabatrina (gama-vinil-GABA) em dor neuropática experimental. Isso foi evidenciado pela diminuição significativa (p<0,05) do comportamento de coçar-se e pelo aumento significativo (p<0,05) da latência de retirada da pata posterior direita a estímulos térmicos nocivos. Isso foi corroborado por achados semelhantes em experimentos com anticonvulsivantes (carbamazepina, fenitoína e ácido valpróico) analgésicos. Esse possível efeito analgésico da vigabatrina (ainda não descrito na literatura) não é mediado pelo sistema opióide. PALAVRAS-CHAVE: vigabatrina, experimental, dor neuropática, comportamento de coçar-se, testes térmicos, ratos Wistar, analgesia.The treatment of chronic neuropathic pain is varied and only partially effective 1 . Davies et al.2 have reported on the use of anticonvulsant and antidepressive drugs in the treatment of chronic neuropathic pain. The anticonvulsant drugs are able of reverting or avoiding seizures. These drugs act by decreasing the neuronal response to seizures-inducing stimuli. Since it is known that in neuropathi...

Antiepileptics and the Treatment of Neuropathic Pain: Evidence from Animal Models

“…As mentioned previously, sodium valproate (15 mg/kg, p.o.) has been reported to attenuate spontaneous pain behaviour and thermal hypersensitivity (although no data was shown) in the CCI model of peripheral nerve injury [162]. However, some supporting evidence has been provided from other animal pain models.…”

“…That only one study to date has tested vigabatrin in an model of neuropathic pain is somewhat surprising given the positive outcome of the study involved. Oral administration of vigabatrin (1 -20 mg/kg) to PNL rats produced a dosedependent reduction in spontaneous pain behaviours [162]. Similarly, the latency to respond to 40°C and 46°C thermal stimuli (used as indices of thermal allodynia and hyperalgesia, respectively) was dose-dependently attenuated by vigabatrin.…”

Mechanism of GABA involvement in post‐traumatic trigeminal neuropathic pain: Activation of neuronal circuitry composed of PKCγ interneurons and pERK1/2 expressing neurons

“…VGB has been shown to have both antinociceptive and analgesic effects under acute and chronic pain conditions (Buckett, 1980;Alves et al, 1999;Czuczwar et al, 2001;Jasmin et al, 2003;Luszczki and Czuczwar, 2008). Moreover, direct microinjection of VGB into the insular cortex in rats resulted in clear and consistent analgesia that was reversed by co-injection with the GABAA receptor antagonist, bicuculline (Jasmin et al, 2003).…”

Newer N-Phthaloyl GABA Derivatives with Antiallodynic and Antihyperalgesic Activities in Both Sciatic Nerve and Spinal Nerve Ligation Models of Neuropathic Pain

“…Intrathecal administration of GABA receptor antagonists dose-dependently produced tactile allodynia [26] , suggesting that inhibiting endogenous GABA can lead to an excited sensory state. In behavioral studies, it has been shown that various chemical analogues of GABA attenuate allodynic and hyperalgesic responses in CCI rats [9,[27][28][29] .…”