(362) Combined serotonin and norepinephrine reuptake inhibition reduces the effects of stress on post-injury pain behaviors in a rat model of burn injury

Abstract

Even with currently available medications, moderate or severe pain after burn injuries is typical and remains a major clinical challenge. There is an urgent need for improvement in the understanding of mechanisms that mediate pain after thermal burn injury in order to reduce patient suffering and enhance recovery. Previous studies suggest that stress may exaggerate pain processing, reduce sensitivity to pain therapeutics, and increase the probability of developing chronic post-burn pain. However, the potential influence of stress has not been incorporated into animal models of thermal burn injury. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to twenty minutes of inescapable swim stress or sham stress once per day for three days. Prior to the first session, and 24 hours following the third session, mechanical and thermal hindpaw sensitivity was recorded. Pain behaviors were determined as the force required to elicit voluntary withdrawal of the hindpaw from a non-noxious mechanical stimulus and the latency to remove the hindpaw from a noxious thermal stimulus. Rats then received a standardized full thickness thermal injury to the right hindpaw and subsequent pain behaviors were recorded at 24 hours, 96 hours, 1 week, 2 weeks, and 3 weeks following thermal injury. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn injury and (2) accelerated the onset of both thermal hyperalgesia and mechanical allodynia after subsequent burn injury. This stress-induced exacerbation of pain sensitivity was reversed by seven days of pretreatment with the SNRI, duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn injury may lead to improved pain treatments for burn injury survivors. Even with currently available medications, moderate or severe pain after burn injuries is typical and remains a major clinical challenge. There is an urgent need for improvement in the understanding of mechanisms that mediate pain after thermal burn injury in order to reduce patient suffering and enhance recovery. Previous studies suggest that stress may exaggerate pain processing, reduce sensitivity to pain therapeutics, and increase the probability of developing chronic post-burn pain. However, the potential influence of stress has not been incorporated into animal models of thermal burn injury. This sham-controlled study evaluated the influence of prior stress exposure on post-burn thermal and mechanical sensitivity in male Sprague-Dawley rats. Rats were exposed to twenty minutes of inescapable swim stress or sham stress once per day for three days. Prior to the first session, and 24 hours following the third session, mechanical and thermal hindpaw sensitivity was recorded. Pain behaviors were determined as the force required to elicit voluntary withdrawal of the hindpaw from a non-noxious mechanical stimulus and the latency to remove the hindpaw from a noxious thermal stimulus. Rats then received a standardized full thickness thermal injury to the right hindpaw and subsequent pain behaviors were recorded at 24 hours, 96 hours, 1 week, 2 weeks, and 3 weeks following thermal injury. Exposure to inescapable swim stress (1) increased the intensity and duration of thermal hyperalgesia after subsequent burn injury and (2) accelerated the onset of both thermal hyperalgesia and mechanical allodynia after subsequent burn injury. This stress-induced exacerbation of pain sensitivity was reversed by seven days of pretreatment with the SNRI, duloxetine. These data suggest a better understanding of mechanisms by which prior stress augments pain after thermal burn injury may lead to improved pain treatments for burn injury survivors.