Intrathecal Co-administration of Morphine Facilitated the Anti-nociceptive of Bupivacaine in a Rat Model of Acute Postoperative Pain

Introduction: Bupivacaine is one of the commonly used agents for spinal anaesthesia. Moreover, co-administration with morphine can likely increase its anti-nociceptive effect bringing about a reduction in the required dose of bupivacaine. Though this has been observed clinically, preclinical studies on the efficacy of this drug combination are lacking. Methods: Sprague Dawley rats, previously implanted with intrathecal catheters, were administered either bupivacaine (30 mcg) or morphine (30 mcg) or both bupivacaine and morphine (15 mcg each). These doses were determined following prior evaluation of different doses of bupivacaine (3, 10 and 30 mcg). Rats were subjected to hind paw incision under isoflurane anaesthesia, 15 min after drug administration. Anti-nociception was evaluated by estimating mechanical allodynia in a fixed peri-incisional area using von Frey filaments. This was done 4 h after the incision. Results: Both bupivacaine and morphine attenuated allodynia though morphine was more effective. Co-administration of both drugs at half the doses increased the antinociceptive effect of bupivacaine to the 30 mcg dose level. Conclusion: The underlying reason for this enhanced anti-nociception could be the different neural mechanisms responsible for anti-nociception. Local anaesthetics inhibit the generation of action potentials by blocking sodium channels whereas opioids like morphine act through G-protein coupled mu opioid receptor-linked closure of calcium channels in presynaptic terminals. In conclusion, the addition of morphine can facilitate bupivacaine’s anti-nociceptive effect following intrathecal administration. This information could have clinical relevance in the treatment of postoperative pain.