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

Abstract

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.

Behavioral assessments of the aversive quality of pain in animals

“…Furthermore, the study of Hummel et al has also shown how this pain-induced aversion is attenuated by a nonanalgesic, non-rewarding dose of morphine [35] . Thus, this paradigm is not only a useful methodology for modeling the sensory and affective components of pain, but also a novel strategy for gaining better insight into the pharmacology of pain-ameliorating therapies for treating pain-related affection.…”

“…In this paradigm, rats subjected to inflammatory-and neuropathic-like pain show a prolonged negative association (for up to one month) with the pain-associated environment enriched with novel objects, after a number of conditioning sessions [35] .…”

“…Accordingly, Hummel et al used novel objects to determine whether animals would interact less frequently with natural reinforcers in the presence of pain, just similar to the human condition [35] .…”

“…In short, this paradigm of modified CPA with novel objects can be used in neuropathic pain models and carrageenan inflammatory model [35] .…”

Behavioural and neurobiological consequences of 2 different chronic stressors in rats

“…There are many reasons to think that pain and mood have a reciprocal interaction. The affective-motivational component of pain is an important determinant of the overall pain experience, and negative affect may cause an increase in the manifestation and expression of pain-related disorders, both in humans (11) and in rodents (12). Although the primary drugs used for the management of chronic pain have traditionally been opioid receptor agonists and nonsteroidal antiinflammatory drugs, antidepressants (such as serotonin noradrenaline reuptake inhibitors and tricyclic antidepressants) are also used to treat chronic pain.…”