GABAPENTIN IN ANIMAL MODELS OF NEUROPATHIC PAIN: A REVIEW ARTICLE OF PHARMACOLOGICAL EFFECTS AND INTERACTIONS WITH PLANT –DERIVED COMPOUNDS

Neuropathic pain arises from lesions or diseases of the somatosensory system that are insufficiently treated with existing drugs. Gabapentin, a ligand of α2δ receptor, is a frequently employed drug, although the underlying mechanism remain poorly understood. This paper critically evaluates 28 provided papers. Six general papers regarding neuropathic pain, pharmacology and animal models of gabapentin: 13 experimental papers on gabapentin in rodents; and 9 papers concerning phytochemicals and their extracts. In case of the papers on gabapentin, they demonstrate antiallodynic or antihyperalgesic properties in models of chronic constriction injury, Spinal nerve ligation, partial sciatic ligation, ischemia, trigeminal and diabetes. Proposed mechanism including inhibition of ectopic discharge, changes in spinal and supraspinal activity, inhibition of nav1.7 and p-ERK1/2 and CaMK II modification. No evidence for GABA receptor or opioid mechanisms was found. One study demonstrated pro inflammatory activity along with antinociceptive effects. Only a small fraction of plant compound studies that have investigated gabapentin combined with the respective plant compounds. Gabapentin- plant combination studies have indicated various interactions, such as synergism and additive effect, among others. Nonetheless, some studies conducted on gabapentin and plants involved the use of gabapentin as the sole positive control but not as an interaction with the plant constituents. This research is limited by model diversity, doses and routes, abstract level data and lack of clinical validation.