Profound Swim Stress-Induced Analgesia with Ketamine

The potential of ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, in preventing central sensitization has led to numerous studies. Ketamine is increasingly used in the clinical setting to provide analgesia and prevent the development of central sensitization at subanaesthetic doses. However, few studies have looked into the potential of ketamine in combination with stress-induced analgesia. This study looks at the effects of swim stress, which is mediated by opioid receptor, on ketamine analgesia using formalin test. Morphine is used as the standard analgesic for comparison. Adult male Sprague-Dawley rats were assigned to 6 groups: 3 groups (stressed groups) were given saline 1ml/kg intraperitoneally (ip), morphine 10mg/kg ip or ketamine 5mg/kg ip and subjected to swim stress; 3 more groups (non-stressed groups) were given the same drugs without swim stress. Formalin test, which involved formalin injection as the pain stimulus and the pain score recorded over time, was performed on all rats ten minutes after cessation of swimming or 30 minutes after injection of drugs. Combination of swim stress and ketamine resulted in complete analgesia in the formalin test which was significantly different from ketamine alone (p<0.05) and saline with stress (p<0.01). There is no significant difference between ketamine stressed and morphine stressed. These results indicate that ketamine and swim stress act synergistically to produce profound analgesia in the formalin test. This suggests that in the clinical setting, under stressful situations such as operative stress, ketamine is capable of producing profound analgesia at a subanaesthetic dose.