Abstract
Neuropathic pain is a kind of pain related with functional abnormality of neurons. Despite large progress in pharmacotherapy, neuropathic pain is still considered an unmet need. Nowadays, there are few drugs registered for this condition, such as pregabalin, gabapentin, duloxetine, carbamazepine, and lidocaine. Among them, pregabalin, gabapentin and carbamazepine are well known antiepileptic drugs. Among the group of new antiepileptic drugs, which are addressed to 1% of human world population suffering from seizures, it turned out that 30% of the seizures resistant to pharmacotherapy has not enough market to justify the costs of drug development. Therefore, it is already a phenomenon that researchers turn their projects toward a larger market, related with possible similar mechanism. Anticonvulsant mechanism of action is in the first place among primary indications for drugs revealing potential analgesic activity. Therefore, many drug candidates for epilepsy, still in preclinical stage, are being evaluated for activity in neuropathic pain. This review is focusing on antiepileptic drugs, which are evaluated for their analgesic activity in major tests related with neuropathic pain. Relation between structure, mechanism of action and result in tests such as the Chung model (spinal nerve ligation SNL), the Bennett model (chronic constriction injury of sciatic nerve CCI) and other tests are considered. The first examples are carbamazepine, gabapentin, and lacosamide as drugs well established in epilepsy market as well as drug candidates such as valnoctamide, and other valproic acid derivatives, novel biphenyl pyrazole derivatives, etc. Moreover, clinical efficacy related with listed animal models has been discussed.
Highlights
Neuropathic pain is a kind of pain caused by functional abnormality of neurons, related with their damage
Among the group of new antiepileptic drugs, which are addressed to 1% of human world population suffering from seizures, it turned out that 30% of the seizures resistant to pharmacotherapy has not enough market to justify the costs of drug development
Among the group of new antiepileptic drugs (AEDs), which are addressed to 1% of human world population suffering from seizures, it turned out that 30% of the seizures resistant to pharmacotherapy has not enough market to justify the costs of drug development
Summary
Neuropathic pain is a kind of pain caused by functional abnormality of neurons, related with their damage. Peripheral neuropathic pain may be caused by mechanical nerve injury, metabolic disease, neurotropic viral disease, neurotoxicity or tumor Those factors may result in pathophysiological changes in peripheral as well as in central nervous system. Voltage-gated sodium channels (NaV), especially their specific isoforms (NaV1.1-NaV1.9), constitute an attractive target in pharmacotherapy of neuropathic pain It has been shown in both animal studies and human tissues that nerve injury induces dynamic regulation of sodium channel expression in dorsal root ganglion [14]. The aim of this review is to show antiepileptic drugs which are evaluated for their analgesic activity in major tests related with neuropathic pain. Some authors have approached similar reviews in the past [12, 13, 23, 24], large progress has been made in terms of knowledge underlying molecular and cellular mechanisms of disease development as well as possible mechanisms of action of potential drugs, and clinical efficacy of drugs
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