The antinociceptive action of thymoquinone on hind paw incision-evoked pain may be associated with modulation of the spinal cord oxidative, inflammatory, and apoptotic pathways

Acute postoperative pain poses a clinical concern due to its potential progression to chronic pain. Conventional systemic and local analgesics are widely used to alleviate acute pain; however, the utility of these drugs is frequently limited by their side effects. Hence, plant-derived alternatives are prompting interest in pain management. Thymoquinone, the primary bioactive constituent of Nigella sativa , has been reported to exhibit antinociceptive properties. This study evaluated the efficacy of thymoquinone in a rat hind paw incision model of acute postsurgical pain, assessing its postoperative effect on mechanical allodynia and its central antinociceptive efficacy via spinal cord antioxidative, anti-inflammatory, and antiapoptotic mechanisms, compared with celecoxib. Acute postoperative pain was induced via a plantar hind paw incision. The rats received thymoquinone or celecoxib orally 4 h and on days 1 and 2 post-surgery, or a single intrathecal dose of these. Mechanical allodynia and locomotor activity were determined using was von Frey filaments and open-field tests. Post-treatment, spinal cord tissues were assayed for oxidative stress, inflammation and apoptosis biomarkers. Plantar incision induced significant mechanical allodynia, evidenced by a marked decrease in paw withdrawal thresholds (PWT) on postoperative days 1–3 in vehicle-treated groups. Oral delivery of thymoquinone (5 and 10 mg/kg) and celecoxib (10 mg/kg) and intrathecal injection of 25 and 200 µg of them attenuated pain hypersensitivity by normalizing PWT without impairing locomotor function. Biochemical outcomes revealed that both thymoquinone and celecoxib effectively mitigated surgery-induced elevations in spinal cord levels of malondialdehyde, TNF-α, and caspase-3, while restoring superoxide dismutase activity. No statistically significant differences were observed between thymoquinone and celecoxib at the corresponding tested doses. Thymoquinone exhibits great antinociceptive activity in postsurgical pain, an effect likely attributable to its concurrent modulation of spinal oxidative stress, neuroinflammation, and apoptotic pathways, with efficacy comparable to that of celecoxib. Equivalent anti-allodynic activity via both oral and intrathecal routes highlights its favorable bioavailability and central target engagement, supporting its potential as a naturally derived alternative in acute postoperative pain management.