Attenuation of nociceptive and paclitaxel-induced neuropathic pain by targeting inflammatory, CGRP and substance P signaling using 3-Hydroxyflavone

Paclitaxel is an anti-microtubule agent, most widely used chemotherapeutic agent for the treatment of malignant solid tumors. However, it associated with some severe side effects including painful neurotoxicity reporting neuropathic pain and sensory abnormalities by patients during after paclitaxel therapy. Peripheral neuropathy was induced administration (4 mg/kg on days 1, 3, 5, 7). In this study, anti-nociceptive anti-inflammatory propensity 3-Hydroxyflavone (3HF) in mice preventive effect 3HF against paclitaxel-induced peripheral Sprague Dawley (SD) rats were investigated. Moreover, tactile cold allodynia, thermal tail immersion hyperalgesia, motor-coordination also evaluated. Furthermore, expression proinflammatory cytokines i.e. Calcitonin gene-related peptide (CGRP), Substance P from spinal cord examined through RT-PCR. Additionally, a computational structural biology approach applied to search potential therapeutic targets predict binding mechanism 3HF. Treatment alleviated nociceptive pain, paw edema, development hyperalgesia. Similarly, suppressed increase mRNA several inflammatory tumor necrosis factor -α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), CGRP, P. daily did not affect motor behaviors rats. The inhibitory predicted extensive bioinformatics which indicates that effectively interacts domains Nuclear factor-kappa B (NF-κB), CGRP receptor exert its activities. computationally affinities revealed compound (Neurokinin 1 receptor) higher than other receptors; there NK1R could be possible target These findings indicate has anti-nociceptive, anti-inflammatory, anti-neuropathic pain.