Back and co-workers demonstrated that intraperitoneal (i.p.) injection of gabapentin at differ-ent doses (30, 100, 300 mg/kg) significantly alleviates mechanical, warm and cold allodynia in partial tail nerve injury-induced neuropathic pain in a dose-dependent manner (Back et al. 2004). Gabapentin is an anticonvulsant and analgesic drug primarily used in the treatment of epilepsy, neuropathic pain, and restless legs syndrome. Though structurally related to gamma-aminobutyric acid (GABA), gabapentin does not bind to GABA receptors or influence GABA metabolism. Gabapentin is an anti-epileptic agent but now it is also recommended as first line agent in neuropathic pain, particularly in diabetic neuropathy and post herpetic neuralgia. α2δ-1, an auxillary subunit of voltage gated calcium channels, has. Gabapentin binds to the α2δ-1 subunit of voltage-gated calcium channels in the CNS, particularly in presynaptic neurons. The inhibition of neurotransmitter release leads to dampened neuronal hyperexcitability, especially in epileptic foci and pain pathways. This review discusses the available evidence for the postulated mechanisms of action of gabapentin. Understanding the mechanism of action of this agent may well lead to the development of safer and more effective antineuropathic drugs. Its effectiveness is attributed to the action of gabapentin in neuropathic pain, where it reduces the excitability of overactive neurons and dampens the transmission of pain signals in both peripheral and central pathways. Gabapentinoids have clinically been used for treating epilepsy, neuropathic pain, and several other neurologic disorders for 30 years; however, the d… Gabapentin is prescribed to treat neuropathic pain, such as pain after shingles (postherpetic neuralgia) and diabetic nerve pain (off-label). It works by blocking abnormal nerve signaling, which helps ease burning, tingling, or shooting pain. In the HIV-associated neuropathic pain report, the review suggested that gabapentin may improve pain and sleep disturbances, however the small sample size of each study and limitations in the analyses conducted prevent strong conclusions. Originally designed as analogs of GABA, the gabapentinoids bind to the α 2 δ ‐1 and α 2 δ ‐2 auxiliary subunits of calcium channels, though only the former has been implicated in the development of neuropathy in animal models.