Effects Of Butorphanol Tartrate Intrathecal Pretreatment On Praxiology And Expression Of Spinal Cord N-methyl- D-aspartate (NMDA) Receptors In Rat Model Of Formalin-induced Inflammatory Pain

Objectives: To explore whether intrathecal pretreatment ofButorphanol could produce a significant analgesia effect in a rat model offormalin-induced inflammatory pain and its mechanism that inhibits theexpression of spinal cord NMDA receptors.Methods: Rats were intrathecally pretreated with saline, low-dose ofButorphanol (12.5μg), and high-dose of Butorphanol (25μg) at 30 minbefore left palmaris paw subcutaneous formalin injection. The controlgroup received no agent prior to formalin injection. For advanced study,the rats were given IT Ketamine which is a non-competitive NMDAreceptor antagonist (50μg, 100μg) or Katemine 50μg with Butorphanol12.5μg at 30 min before formalin injection. After injection, theformalin-induced behavior was recorded continuously for 60 min.Formalin injection produced a characteristic behavior consisting offlinching and licking/biting of the injected paw. Rats were killed 2 h afterthe formalin injection, and the expression of NMDA receptors of the fifthlumbar spinal cord was determined by histoimmunology.Results: IT high-dose Butorphanol (25μg) or Katemine 50μg withButorphanol 12.5μg were both capable of inhibiting both phases offormalin response. However, the expression of both the early and laterphases was not significantly affected in other groups. Intrathecalpretreatment of high-dose Butorphanol (25μg) or Katemine 50μg withButorphanol 12.5μg both lowered the expression of spinal cord NMDAreceptors.Conclusion: 1.The results provided evidence that the intrathecalinjection of butorphanol has been demonstrated to produce adose-dependent antinociception(significant analgesic effect at 25μg).in a rat model of formalin-induced inflammatory pain. The mechanismsof analgesia may be that butorphanol to restrain the stimulation ofNMDA receptors. 2.This two doeses ketamine (50,100μg) could notinhibit the pain responses to formalin. 3. The intrathecal pre-treatment ofa combination of 12.5μg of butorphanol and 50μg of ketamine couldproduce coe-antinociceptive effects which the consequence ofcoe-inhibition in expression of NMDA receptors.