The persistence of a long-term negative affective state following the induction of either acute or chronic pain

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Clinically, pain is a complex phenomenon consisting of both sensory and affective aberrations that can persist indefinitely. Pre-clinically, several animal paradigms have been established that reliably mimic both the acute and chronic aspects of pain pertinent to the human condition; however, the commonly used behavioral models only assess the sensory component of pain elicited by an evoked nociceptive stimulus. Since the affective-motivational component of pain is an important determinant of the overall pain experience in man, we investigated how this aspect may be modeled long-term in rats using novel objects and a modified conditioned place aversion (CPA) paradigm. Findings demonstrate that animals subjected to either neuropathic injury or inflammatory insult display a significant conditioned place aversion to a pain-paired environment that is paralleled by an increased number of hind paw withdrawals and fewer number of novel object interactions during painful conditioning sessions. Moreover, this aversion is maintained for 1 month in the absence of further conditioning. We also determined that a non-analgesic, non-rewarding dose of morphine administered prior to pain-paired conditioning sessions attenuates the pain-induced aversion and its relative persistence in both pain models. Together, these findings underscore the importance of negative affect accompanying painful conditions and its long-term persistence even when the injury or insult has resolved. Lastly, these results suggest how both sensory and affective aberrations associated with neuropathic- and inflammatory-like conditions and the memory of such known to impact quality of life in man may be addressed pre-clinically in rodents.

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