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  1. Article ; Online: Cognition in the Chronic Pain Experience: Preclinical Insights.

    Phelps, Caroline E / Navratilova, Edita / Porreca, Frank

    Trends in cognitive sciences

    2021  Volume 25, Issue 5, Page(s) 365–376

    Abstract: Acutely, pain is protective. It promotes escape from, and future avoidance of, noxious stimuli through strong and often lifetime associative memories. However, with persistent acute pain or when pain becomes chronic, these memories can promote negative ... ...

    Abstract Acutely, pain is protective. It promotes escape from, and future avoidance of, noxious stimuli through strong and often lifetime associative memories. However, with persistent acute pain or when pain becomes chronic, these memories can promote negative emotions and poor decisions often associated with deleterious behaviors. In this review, we discuss how preclinical studies can provide insights into the relationship between cognition and chronic pain. We also discuss the concept of pain as a cognitive disorder and new strategies for treating chronic pain that emphasize inhibiting the formation of pain memories or promoting 'forgetting' of established pain memories.
    MeSH term(s) Chronic Pain ; Cognition ; Emotions ; Humans ; Memory
    Language English
    Publishing date 2021-01-25
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2010989-1
    ISSN 1879-307X ; 1364-6613
    ISSN (online) 1879-307X
    ISSN 1364-6613
    DOI 10.1016/j.tics.2021.01.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Chronic Pain Produces Reversible Memory Deficits That Depend on Task Difficulty in Rats.

    Phelps, Caroline E / Navratilova, Edita / Porreca, Frank

    The journal of pain

    2021  Volume 22, Issue 11, Page(s) 1467–1476

    Abstract: Cognitive impairment associated with chronic pain remains relatively poorly understood. Use of analgesic drugs and often present co-morbidities in patients can preclude conclusions of causative relationships between chronic pain and cognitive deficits. ... ...

    Abstract Cognitive impairment associated with chronic pain remains relatively poorly understood. Use of analgesic drugs and often present co-morbidities in patients can preclude conclusions of causative relationships between chronic pain and cognitive deficits. Here, the impact of pain resulting from spinal nerve ligation (SNL) injury in rats on short and long-term memory was assessed in the novel object recognition task. To understand if chronic pain seizes the limited cognitive resources that are available at any given time, task difficulty was varied by using either very different (ie, easy task) or similar (ie, difficult task) pairs of objects. Nerve-injured, male rats exhibited no short or long-term memory deficits under easy task conditions. However, unlike sham-operated controls, injured rats showed deficits in both short and long-term memory by failing to differentiate similar objects in the difficult task version. In SNL rats, duloxetine produced anti-allodynic effects and ameliorated long-term memory deficits in the difficult task suggesting benefits of pain relief possibly complemented by noradrenergic mediated cognitive enhancement. Together these data suggest chronic pain reversibly takes up a significant amount of limited cognitive resources, leaving sufficient available for easy, but not difficult, tasks. PERSPECTIVE: Memory deficits in a rat model of chronic pain were only seen when the cognitive load was high, ie, in a difficult task. Acute treatment with duloxetine was sufficient to relieve memory deficits, suggesting chronic pain induces memory deficits by seizing limited cognitive resources to the detriment of task-related stimuli.
    MeSH term(s) Animals ; Chronic Pain/complications ; Chronic Pain/drug therapy ; Chronic Pain/physiopathology ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/physiopathology ; Disease Models, Animal ; Duloxetine Hydrochloride/administration & dosage ; Duloxetine Hydrochloride/pharmacology ; Male ; Neuralgia/complications ; Neuralgia/drug therapy ; Neuralgia/physiopathology ; Psychomotor Performance/drug effects ; Psychomotor Performance/physiology ; Rats ; Rats, Sprague-Dawley ; Recognition, Psychology/drug effects ; Recognition, Psychology/physiology ; Serotonin and Noradrenaline Reuptake Inhibitors/administration & dosage ; Serotonin and Noradrenaline Reuptake Inhibitors/pharmacology
    Chemical Substances Serotonin and Noradrenaline Reuptake Inhibitors ; Duloxetine Hydrochloride (9044SC542W)
    Language English
    Publishing date 2021-05-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2018789-0
    ISSN 1528-8447 ; 1526-5900
    ISSN (online) 1528-8447
    ISSN 1526-5900
    DOI 10.1016/j.jpain.2021.04.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5237: Show issues Location:
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  3. Article ; Online: The partial saphenous nerve injury model of pain impairs reward-related learning but not reward sensitivity or motivation.

    Phelps, Caroline E / Lumb, Bridget M / Donaldson, Lucy F / Robinson, Emma S

    Pain

    2021  Volume 162, Issue 3, Page(s) 956–966

    Abstract: Abstract: Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated ... ...

    Abstract Abstract: Chronic pain is highly comorbid with affective disorders, including major depressive disorder. A core feature of major depressive disorder is a loss of interest in previously rewarding activities. Major depressive disorder is also associated with negative affective biases where cognitive processes are modulated by the affective state. Previous work from our laboratory has shown that reward-related learning and memory is impaired in rodent models of depression generated through a variety of different manipulations. This study investigated different aspects of reward-related behaviour in a rodent model of chronic pain, the partial saphenous nerve injury (PSNI). Using our reward-learning assay, an impairment in reward learning was observed with no difference in sucrose preference, consistent with a lack of effect on reward sensitivity and similar to the effects seen in depression models. In a successive negative contrast task, chronic pain was not associated with changes in motivation for reward either under normal conditions or when reward was devalued although both sham and PSNI groups exhibited the expected negative contrast effect. In the affective bias test, PSNI rats developed a positive affective bias when treated with gabapentin, an effect not seen in the controls suggesting an association with the antinociceptive effects of the drug inducing a relatively more positive affective state. Together, these data suggest that there are changes in reward-related cognition in this chronic pain model consistent with previous findings in rodent models of depression. The effects seen with gabapentin suggest that pain-associated negative affective state may be remediated by this atypical analgesic.
    MeSH term(s) Animals ; Depressive Disorder, Major ; Learning ; Motivation ; Pain/etiology ; Rats ; Reward
    Language English
    Publishing date 2021-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000002177
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Differential impacts of healthy cognitive aging on directed and random exploration.

    Mizell, Jack-Morgan / Wang, Siyu / Frisvold, Alec / Alvarado, Lily / Farrell-Skupny, Alex / Keung, Waitsang / Phelps, Caroline E / Sundman, Mark H / Franchetti, Mary-Kathryn / Chou, Ying-Hui / Alexander, Gene E / Wilson, Robert C

    Psychology and aging

    2024  Volume 39, Issue 1, Page(s) 88–101

    Abstract: Deciding whether to explore unknown opportunities or exploit well-known options is a ubiquitous part of our everyday lives. Extensive work in college students suggests that young people make explore-exploit decisions using a mixture of information ... ...

    Abstract Deciding whether to explore unknown opportunities or exploit well-known options is a ubiquitous part of our everyday lives. Extensive work in college students suggests that young people make explore-exploit decisions using a mixture of information seeking and random behavioral variability. Whether, and to what extent, older adults use the same strategies is unknown. To address this question, 51 older adults (ages 65-74) and 32 younger adults (ages 18-25) completed the Horizon Task, a gambling task that quantifies information seeking and behavioral variability as well as how these strategies are controlled for the purposes of exploration. Qualitatively, we found that older adults performed similar to younger adults on this task, increasing both their information seeking and behavioral variability when it was adaptive to explore. Quantitively, however, there were substantial differences between the age groups, with older adults showing less information seeking overall and less reliance on variability as a means to explore. In addition, we found a subset of approximately 26% of older adults whose information seeking was close to zero, avoiding informative options even when they were clearly the better choice. Unsurprisingly, these "information avoiders" performed worse on the task. In contrast, task performance in the remaining "information seeking" older adults was comparable to that of younger adults suggesting that age-related differences in explore-exploit decision making may be adaptive except when they are taken to extremes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
    MeSH term(s) Humans ; Aged ; Adolescent ; Young Adult ; Adult ; Cognitive Aging ; Aging ; Gambling ; Healthy Aging ; Students
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 635596-1
    ISSN 1939-1498 ; 0882-7974
    ISSN (online) 1939-1498
    ISSN 0882-7974
    DOI 10.1037/pag0000791
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    Zs.A 3194: Show issues Location:
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  5. Article ; Online: Kappa opioid signaling in the right central amygdala causes hind paw specific loss of diffuse noxious inhibitory controls in experimental neuropathic pain.

    Phelps, Caroline E / Navratilova, Edita / Dickenson, Anthony H / Porreca, Frank / Bannister, Kirsty

    Pain

    2019  Volume 160, Issue 7, Page(s) 1614–1621

    Abstract: Diffuse noxious inhibitory controls (DNICs) is a pain-inhibits-pain phenomenon demonstrated in humans and animals. Diffuse noxious inhibitory control is diminished in many chronic pain states, including neuropathic pain. The efficiency of DNIC has been ... ...

    Abstract Diffuse noxious inhibitory controls (DNICs) is a pain-inhibits-pain phenomenon demonstrated in humans and animals. Diffuse noxious inhibitory control is diminished in many chronic pain states, including neuropathic pain. The efficiency of DNIC has been suggested to prospectively predict both the likelihood of pain chronification and treatment response. Little is known as to why DNIC is dysfunctional in neuropathic pain. Here, we evaluated DNIC in the rat L5/L6 spinal nerve ligation (SNL) model of chronic pain using both behavioral and electrophysiological outcomes. For behavior, nociceptive thresholds were determined using response to noxious paw pressure on both hind paws as the test stimulus before, and after, injection of a conditioning stimulus of capsaicin into the left forepaw. Functionally, the spike firing of spinal wide-dynamic-range neuronal activity was evaluated before and during noxious ear pinch, while stimulating the ipsilateral paw with von Frey hairs of increased bending force. In both assays, the DNIC response was significantly diminished in the ipsilateral (ie, injured) paw of SNL animals. However, behavioral loss of DNIC was not observed on the contralateral (ie, uninjured) paw. Systemic application of nor-binaltorphimine, a kappa opioid antagonist, did not ameliorate SNL-induced hyperalgesia but reversed loss of the behavioral DNIC response. Microinjection of nor-binaltorphimine into the right central amygdala (RCeA) of SNL rats did not affect baseline thresholds but restored DNIC both behaviorally and electrophysiologically. Cumulatively, these data suggest that net enhanced descending facilitations may be mediated by kappa opioid receptor signaling from the right central amygdala to promote diminished DNIC after neuropathy.
    MeSH term(s) Amygdala/physiopathology ; Animals ; Chronic Pain/physiopathology ; Diffuse Noxious Inhibitory Control/drug effects ; Electrophysiological Phenomena ; Functional Laterality ; Hindlimb/innervation ; Hindlimb/physiopathology ; Hyperalgesia/drug therapy ; Hyperalgesia/physiopathology ; Ligation ; Male ; Naltrexone/analogs & derivatives ; Naltrexone/pharmacology ; Neuralgia/physiopathology ; Neuralgia/psychology ; Pain Measurement ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa/antagonists & inhibitors ; Receptors, Opioid, kappa/drug effects ; Signal Transduction ; Spinal Nerves/physiopathology
    Chemical Substances Receptors, Opioid, kappa ; norbinaltorphimine (36OOQ86QM1) ; Naltrexone (5S6W795CQM)
    Language English
    Publishing date 2019-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000001553
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  6. Article ; Online: A pain-induced tonic hypodopaminergic state augments phasic dopamine release in the nucleus accumbens.

    Gee, Taylor A / Weintraub, Nathan C / Lu, Dong / Phelps, Caroline E / Navratilova, Edita / Heien, Michael L / Porreca, Frank

    Pain

    2020  Volume 161, Issue 10, Page(s) 2376–2384

    Abstract: Diseases and disorders such as Parkinson disease, schizophrenia, and chronic pain are characterized by altered mesolimbic dopaminergic neurotransmission. Dopamine release in the nucleus accumbens influences behavior through both tonic and phasic ... ...

    Abstract Diseases and disorders such as Parkinson disease, schizophrenia, and chronic pain are characterized by altered mesolimbic dopaminergic neurotransmission. Dopamine release in the nucleus accumbens influences behavior through both tonic and phasic signaling. Tonic dopamine levels are hypothesized to inversely regulate phasic signals through dopamine D2 receptor feedback inhibition. We tested this hypothesis directly in the context of ongoing pain. Tonic and phasic dopamine signals were measured using fast-scan controlled-adsorption voltammetry and fast-scan cyclic voltammetry, respectively, in the nucleus accumbens shell of male rats with standardized levels of anesthesia. Application of capsaicin to the cornea produced a transient decrease in tonic dopamine levels. During the pain-induced hypodopaminergic state, electrically evoked phasic dopamine release was significantly increased when compared to baseline, evoked phasic release. A second application of capsaicin to the same eye had a lessened effect on tonic dopamine suggesting desensitization of TRPV1 channels in that eye. Capsaicin treatment in the alternate cornea, however, again produced coincident decreased dopaminergic tone and increased phasic dopamine release. These findings occurred independently of stimulus lateralization relative to the hemisphere of dopamine measurement. Our data show that (1) the mesolimbic dopamine circuit reliably encodes acute noxious stimuli; (2) ongoing pain produces decreases in dopaminergic tone; and (3) pain-induced decreases in tonic dopamine correspond to augmented evoked phasic dopamine release. Enhanced phasic dopamine neurotransmission resulting from salient stimuli may contribute to increased impulsivity and cognitive deficits often observed in conditions associated with decreased dopaminergic tone, including Parkinson disease and chronic pain.
    MeSH term(s) Animals ; Dopamine ; Male ; Nucleus Accumbens ; Pain ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2
    Chemical Substances Receptors, Dopamine D2 ; Dopamine (VTD58H1Z2X)
    Language English
    Publishing date 2020-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000001925
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  7. Article ; Online: Chronic pain impairs cognitive flexibility and engages novel learning strategies in rats.

    Cowen, Stephen L / Phelps, Caroline E / Navratilova, Edita / McKinzie, David L / Okun, Alec / Husain, Omar / Gleason, Scott D / Witkin, Jeffrey M / Porreca, Frank

    Pain

    2018  Volume 159, Issue 7, Page(s) 1403–1412

    Abstract: Cognitive flexibility, the ability to adapt behavior to changing outcomes, is critical to survival. The prefrontal cortex is a key site of cognitive control, and chronic pain is known to lead to significant morphological changes to this brain region. ... ...

    Abstract Cognitive flexibility, the ability to adapt behavior to changing outcomes, is critical to survival. The prefrontal cortex is a key site of cognitive control, and chronic pain is known to lead to significant morphological changes to this brain region. Nevertheless, the effects of chronic pain on cognitive flexibility and learning remain uncertain. We used an instrumental paradigm to assess adaptive learning in an experimental model of chronic pain induced by tight ligation of the spinal nerves L5/6 (spinal nerve ligation model). Naive, sham-operated, and spinal nerve ligation (SNL) rats were trained to perform fixed-ratio, variable-ratio, and contingency-shift behaviors for food reward. Although all groups learned an initial lever-reward contingency, learning was slower in SNL animals in a subsequent choice task that reversed reinforcement contingencies. Temporal analysis of lever-press responses across sessions indicated no apparent deficits in memory consolidation or retrieval. However, analysis of learning within sessions revealed that the lever presses of SNL animals occurred in bursts, followed by delays. Unexpectedly, the degree of bursting correlated positively with learning. Under a variable-ratio probabilistic task, SNL rats chose a less profitable behavioral strategy compared with naive and sham-operated animals. After extinction of behavior for learned preferences, SNL animals reverted to their initially preferred (ie, less profitable) behavioral choice. Our data suggest that in the face of uncertainty, chronic pain drives a preference for familiar associations, consistent with reduced cognitive flexibility. The observed burst-like responding may represent a novel learning strategy in animals with chronic pain.
    MeSH term(s) Animals ; Chronic Pain/etiology ; Chronic Pain/psychology ; Cognition/physiology ; Decision Making/physiology ; Executive Function/physiology ; Learning/physiology ; Male ; Peripheral Nerve Injuries/complications ; Peripheral Nerve Injuries/psychology ; Rats ; Rats, Sprague-Dawley
    Language English
    Publishing date 2018-04-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000001226
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