Antiepileptic drugs for treatment of neuropathic pain

Abstract

Neuropathic pain, a form of chronic pain, caused by injury or disease of the peripheral or central nervous system, is a therapeutic challenge to clinicians because it does not respond well to traditional pain therapies. Basic research of pathophysiological mechanisms of neuropathic pain has shown many similarities between the morphological and biochemical changes observed in epilepsy and neuropathic pain, which gave the rational for examination and use of antiepileptic drugs (AED) in management of neuropathic pain disorders. Carbamazepine was the first AED studied in clinical trials, achieving positive results predominantly in the treatment of trigeminal neuralgia, and took its place in therapy of this particular neuropathic pain disorder. Gabapentin, a newer AED, has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia and is considered the first choice of therapy for neuropathic pain. There is increasing evidence that effect in both experimental and clinical studies. Due to less frequency and severity of adverse effects it is considered as an alternative to carbamazepine in a treatment of neuropathic pain. There is insufficient evidence about efficacy of phenitoin, lamotrigine and some others AED in the treatment of neuropathic pain disorders. Future advances in treatment of neuropathic pain are directed on understanding the pathophysiological mechanisms underlying neuropathic pain and further examining the mechanisms of action of AED, and their efficacy and safety in treatment of neuropathic pain.

Neuropatski bol je oblik hroničnog bola izazvan povredom ili oboljenjem perifernog ili centralnog nervnog sistema. Predstavlja terapijski izazov za kliničare, jer se primenom konvencionalnih analgetika u terapiji ovog tipa bola ne postižu zadovoljavajući rezultati. Bazična istraživanja patofizioloških mehanizama neuropatskog bola pokazala su mnoge sličnosti između morfoloških i biohemijskih promena koje se javljaju kod neuropatskog bola i onih koje se javljaju kod epilepsije, što čini osnovu za ispitivanje i upotrebu antiepileptika u terapiji ovog tipa bola. Prvi klinički ispitani antiepileptik, karbamazepin, ostvario je pozitivne rezultate prevashodno u terapiji neuralgije trigeminusa, gde je i našao svoje mesto u kliničkoj praksi. Lek novije generacije, gabapentin, je za sada najjasnije pokazao analgetičko dejstvo kod neuropatskog bola, posebno kod dijabetičke neuropatije i postherpetičke neuralgije i danas se smatra lekom prvog izbora u terapiji neuropatskih bolnih stanja. Sve je više dokaza o analgetičkom dejstvu okskarbazepina, koji je keto-derivat karbamazepina. U eksperimentalnim i kliničkim ispitivanjima okskarbazepin se pokazao kao moguća zamena za karbamazepin u terapiji neuropatskog bola, zbog niže učestalosti i manjeg intenziteta neželjenih efekata. Znatno je manje dokaza o efikasnosti fenitoina, lamotrigina i nekih drugih antiepileptika u suzbijanju neuropatskog bola. Dalje usavršavanje terapije neuropatskog bola usmereno je ka rasvetljavanju njegovih složenih patofizioloških mehanizama, kao i daljem ispitivanju mehanizama dejstva, efikasnosti i bezbednosti primene antiepileptika u terapiji neuropatskog bola.