Cervicomedullary intrathecal injection of morphine produces antinociception in the orofacial formalin test in the rat

Abstract

Background: High cervical and medullary drug delivery has been advocated for the treatment of refractory head and neck pain in humans. Currently, parallel models in animals have not been developed to support this methodology. We combined an accepted animal model of pain of cranial origin with a novel technique of neuraxial drug delivery to address this issue. Methods: Male Wistar rats were implanted with intrathecal catheters that were advanced cephalad through a lumbar guide cannula to the high cervical spinal cord. The orofacial formalin test was used to assess antinociception. Vehicle or morphine (1, 3, 6, 10, 30 μg) was injected intrathecally followed 10 minutes later by injection of formalin solution, 2.5%, into the vibrissal pad. Motor assessment and hemodynamic and respiratory blood gas measurements were evaluated in a separate group of animals. Results: Intrathecal morphine produced a dose-dependent decrease in the first and second phases of the behavioral response (P < 0.05). The ED50 (95% confidence limits) values for the first and second phases were 6.65 μg (3.52-14.9 μg) and 3.40 μg (2.37-4.61 μg), respectively. Ten micrograms intrathecal naloxone antagonized the morphine effect (P < 0.05). Significant cardiovascular and respiratory depression was observed. No significant motor dysfunction was observed. Conclusions: Cervicomedullary injection of morphine produced antinociception in the orofacial formalin test in the rat. This animal model may be useful to assess analgesics designed for parallel clinical application in humans.