Gabapentin and Pregabalin for the Treatment of Neuropathic Pain: A Review of Laboratory and Clinical Evidence

Gabapentin (Neurontin, Pfizer Canada Inc) and pregabalin (Lyrica, Pfizer Canada Inc) were initially developed as antiepileptic drugs and were later discovered to be effective in the treatment of neuropathic pain, creating a relatively novel class of analgesic drugs. The present article reviews the laboratory data on the antinociceptive effects of these drugs in animal models of neuropathic pain, and the clinical trial data on their effects in patients with various neuropathic pain syndromes. Laboratory evidence suggests that both gabapentin and pregabalin can inhibit hyperalgesia and allodynia evoked by a variety of neural insults, including peripheral trauma, diabetes and chemotherapy. Current opinion suggests these antinociceptive effects occur because of drug interaction with the 2 subunit of voltage-gated calcium channels. The majority of clinical evidence supports analgesic efficacy in diabetic neuropathy and postherpetic neuralgia, and limited evidence suggests that this efficacy extends to other, but not necessarily all, neuropathic pain syndromes. Early comparative trials and pooled estimates from meta-analyses suggest that analgesic efficacy of gabapentin and pregabalin is perhaps slightly lower than that of tricyclic antidepressants or opioids. However, the most attractive aspects of these two drugs include their tolerability, lack of serious toxicity and ease of use. Future research efforts are warranted to fully understand the mechanism of action of these drugs, to clearly characterize the safety and efficacy of gabapentin and pregabalin in all clinical neuropathic pain syndromes, and to further explore the role of these drugs in the rational polypharmacy of neuropathic pain.