Chronic Inflammatory Pain Management by BDNF Modulation: A Comparative Study of Gabapentin, Indomethacin and Their Combination on Arthritis Rat Model
Brain derived neurotropic factors (BDNF) can be secreted either as a pro-BDNF or a mature form (mBDNF) through γ-amino-butyric acid (GABAA) receptors activation. Depolarization of GABA neurons in spinal cord can be mediated through N-methyl-D-aspartate (NMDA) receptor due to the exogenous secretion of over expressed BDNF. This over expressed BDNF further modulate the excitation and sensitization of nociceptors. We investigated the modulation of BDNF by GABAA agonist i.e., gabapentin,
... n (non-steroidal anti-inflammatory) and their low-dose combination on adjuvant-induced inflammatory arthritis. Mycobacterium tuberculosis H37Ra strain, as adjuvant, was injected in the tail base of female Sprague-Dawley rats. Gabapentin (5 mg/kg), indomethacin (5 mg/kg) and low dose combination of gabapentin (1.5 mg/kg) + indomethacin (2.5 mg/kg) were used. Paw edema was measure by plethysmometer and chronic pain was measured by plantar apparatus. Nitric oxide, peroxide and superoxide dismutase levels were also measured to analyze the free radical and antioxidant balance in different treatment groups along with the total protein concentration. Significant reduction of nitric oxide, peroxide as well as total protein concentration was found in low dose combination. Immunohistochemistry data also showed that the low dose combination has more potential in lowering the BDNF expression in cortex as well as in hippocampus region of brain as compared to their mono therapies. Our study suggested that low-dose combination of gabapentin and indomethacin has a significant impact on lowering the chronic and its associated markers as compare to their monotherapy. Thus indicated the additive effects of the combination therapy on neuropathic pain.