Comparative activity of the anti-convulsants oxcarbazepine, carbamazepine, lamotrigine and gabapentin in a model of neuropathic pain in the rat and guinea-pig
Autor: | Stuart Bevan, Alyson Fox, Adam Kesingland, Clive Gentry, Sadhana Patel |
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Rok vydání: | 2003 |
Předmět: |
Male
Pain Threshold Cyclohexanecarboxylic Acids Gabapentin Guinea Pigs Analgesic Oxcarbazepine Acetates Pharmacology Lamotrigine Pressure medicine Animals Amines Rats Wistar gamma-Aminobutyric Acid Triazines business.industry Carbamazepine Sciatic Nerve Rats Anesthesiology and Pain Medicine Allodynia Neurology Hyperalgesia Touch Neuropathic pain Neuralgia Wounds and Injuries Anticonvulsants Neurology (clinical) medicine.symptom business medicine.drug |
Zdroj: | Pain. 105:355-362 |
ISSN: | 0304-3959 |
DOI: | 10.1016/s0304-3959(03)00253-7 |
Popis: | Anti-epileptic drugs (AEDs) are increasingly used for the treatment of neuropathic pain. Oxcarbazepine is a recently introduced AED that is effective in treating epilepsy and has an improved side-effect profile compared to existing therapies. Here we have examined the effect of oxcarbazepine and other AEDs in a model of neuropathic pain in the rat and guinea-pig. Oxcarbazepine and carbamazepine (3-100 mg x kg(-1)) did not affect mechanical hyperalgesia or tactile allodynia induced by partial sciatic nerve ligation in the rat following oral administration. However, in the same model in the guinea-pig, both drugs produced up to 90% reversal of mechanical hyperalgesia with respective D(50) values of 10.7 and 0.8 mg x kg(-1). The active human metabolite of oxcarbazepine, monohydroxy derivative, was similarly active against mechanical hyperalgesia in the guinea-pig but not the rat. Lamotrigine (3-100 mg x kg(-1), p.o.) was effective against mechanical hyperlagesia in both species although it showed greater efficacy and potency in the guinea-pig (D(50) 4.7 mg x kg(-1)) compared to the rat (D(50) 27 mg kg(-1)). Lamotrigine produced slight inhibition of tactile allodynia in the rat only at the highest dose tested of 100 mg x kg(-1). Gabapentin was poorly active against mechanical hyperalgesia in both the rat and guinea-pig following a single oral administration (100 mg x kg(-1)), although upon repeated administration it produced up to 70 and 90% reversal in rat and guinea-pig, respectively. Gabapentin did however produce significant dose-related reversal of tactile allodynia in the rat following a single administration. These data show that oxcarbazepine and other AEDs are effective anti-hyperalgesic or anti-allodynic agents in an animal model of neuropathic pain, and provide further support for their use in the treatment of neuropathic pain in the clinic. |
Databáze: | OpenAIRE |
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