title: Disruption of persistent nociceptive behavior in rats with learning impairment.
abstract: Despite 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.
authors.affiliation: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America ; Department of Anatomy, School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China ; Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Ma
authors.forename: Shuxing
authors.initials: S
authors.lastname: Wang
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tian
authors.forename: Lucy
authors.initials: L
authors.lastname: Chen
authors.forename: Guoying
authors.initials: G
authors.lastname: Li
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage; D000818:Animals; D000842:Ankle / Q000503:physiopathology; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D003513:Cycloheximide / Q000008:administration & dosage; D005620:Freund's Adjuvant / Q000008:administration & dosage; D015870:Gene Expression; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007858:Learning; D008297:Male; D059225:Nociception; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D005620:Freund's Adjuvant; D003513:Cycloheximide; C087857:protein kinase C gamma; D011493:Protein Kinase C
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