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.

Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain

“…Chronic pain has been conceptualized as a type of long-term learning ( Apkarian et al, 2011 ), characterized by accumulation of nociceptive memory ( Yi and Zhang, 2011 ) and inability to extinguish negative emotional associations and anxiety ( Mutso et al, 2013; Ploghaus et al, 2001; Vachon-Presseau et al, 2013 ), in which both Hpc and mPFC are involved ( Carter et al, 2006; Lang et al, 2009 ). In rats, disrupting hippocampal function has been shown to reverse persistent nociception ( Ma et al, 2013 ). In humans, a recently proposed model of aversive prediction error in pain learning has suggested the PAG as the primary hub in the pain learning neural network ( Roy et al, 2014 ) relying on mPFC and Hpc.…”

Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease

“…Mirroring clinical populations most studies report altered pain thresholds compared with controls. 7 , 59 , 67 , 94 , 99 , 105 , 133 , 137 A chemically induced model of osteoarthritis through an intra-articular injection of monosodium iodoacetate within transgenic TASTPM AD mice has provided insights into interactions between clinically relevant pain, neurodegenerative pathophysiology, and opioid analgesia. 4 , 5 TASTPM mice demonstrate an age-dependent reduction in thermal nociception that coincides with amyloid pathology in pain-related brain regions.…”

Inhibition of the cAMP/PKA/CREB Pathway Contributes to the Analgesic Effects of Electroacupuncture in the Anterior Cingulate Cortex in a Rat Pain Memory Model

“…It should also be noted that pain sensory could be affected by pain memory vice versa [28]. Through the top-down manipulation, the information from evaluative-cognitive modulation could exert pain perception on the others [3, 29]. Actually, pain memory is a complex perception experience.…”

“…To explore the effective therapy and the potential mechanisms of pain memory, affective-motivational and evaluative-cognitive pain have increasingly gained researchers' attentions [2, 3, 26, 28, 33]. EA, an effective pain treatment that is considered to be a mind-body therapy, has a wide range of data supporting its analgesic role and capacity to regulate mood disorder and memory [2, 23, 34, 35].…”

“…It is a nociceptive pain characterized by hyperalgesia and allodynia, resulting in formation of memories and negative emotions of pain in the brain [3–6]. This process consists of acquisition, consolidation, and retrieval of pain [7, 8].…”