Ma, YuxinWang, ShuxingTian, YinghongChen, LucyLi, GuoyingMao, Jianren2014-03-102013Ma, Yuxin, Shuxing Wang, Yinghong Tian, Lucy Chen, Guoying Li, and Jianren Mao. 2013. “Disruption of Persistent Nociceptive Behavior in Rats with Learning Impairment.” PLoS ONE 8 (9): e74533. doi:10.1371/journal.pone.0074533. http://dx.doi.org/10.1371/journal.pone.0074533.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11877062Despite the subjective nature of pain experience with cognitive and affective dimensions, preclinical pain research has largely focused on its sensory dimension. Here, we examined the relationship between learning/memory and nociceptive behavior in rats with combined learning impairment and persistent nociception. Learning impairment was induced by bilateral hippocampal injection of a mixed Aβ solution, whereas persistent nociception produced in these rats by complete Freund’s adjuvant-induced ankle inflammation. Those rats with learning impairment showed a diminished development of thermal hyperalgesia and mechanical allodynia and a shorter time course of nociceptive behavior without alteration of their baseline nociceptive threshold. In rats with pre-established hyperalgesia and allodynia due to ankle inflammation, bilateral intra-hippocampal injection of cycloheximide (a protein synthesis inhibitor) promoted the earlier recovery of nociceptive behavior. Moreover, expression of Aβ, NR1 subunit of the N-methyl-D-aspartate receptor, and protein kinase Cγ was upregulated, whereas the choline acetyl transferase expression was downregulated, in the hippocampus, thalamus, amygdala, and/or spinal cord of rats with combined learning impairment and persistent nociception. The data indicate that learning impairment could disrupt the response to a state of persistent nociception, suggesting an important role for cognitive maladaptation in the mechanisms of chronic pain. These results also suggest that a preclinical model of combined learning impairment and persistent nociception may be useful to explore the brain mechanisms underlying the transition from acute to chronic pain.en-USJournal Article2014-03-1010.1371/journal.pone.0074533