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

Pain. 2008 Dec;140(3):436-445. doi: 10.1016/j.pain.2008.09.020. Epub 2008 Oct 21.


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.

MeSH terms

  • Acute Disease / psychology
  • Analgesics, Opioid / pharmacology
  • Animals
  • Anxiety Disorders / etiology
  • Anxiety Disorders / physiopathology
  • Anxiety Disorders / psychology*
  • Avoidance Learning / physiology
  • Carrageenan
  • Chronic Disease / psychology
  • Conditioning, Psychological / physiology
  • Depressive Disorder / etiology
  • Depressive Disorder / physiopathology
  • Depressive Disorder / psychology*
  • Disease Models, Animal
  • Inflammation / chemically induced
  • Inflammation / physiopathology
  • Inflammation / psychology
  • Inflammation Mediators
  • Mood Disorders / etiology
  • Mood Disorders / physiopathology
  • Mood Disorders / psychology*
  • Morphine / pharmacology
  • Pain / complications
  • Pain / physiopathology
  • Pain / psychology*
  • Rats
  • Stress, Psychological / etiology
  • Stress, Psychological / physiopathology
  • Stress, Psychological / psychology*
  • Time


  • Analgesics, Opioid
  • Inflammation Mediators
  • Morphine
  • Carrageenan