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.

Highlights

  • Chronic pain is highly comorbid with affective disorders including major depressive disorder (MDD).[3,33] Despite this, it is not yet understood whether this comorbidity arises through overlapping neurobiology[63] or independent mechanisms.[6]

  • Results from the different measures of reward processing revealed dissociable effects with rats from the nerve injury group exhibiting an attenuated rewardinduced positive bias. These effects were not related to changes in reward sensitivity in the sucrose preference tests (SPTs) or changes in reward motivation. These findings concur with recent data obtained from putative models of depression suggesting that rats experiencing chronic pain exhibit similar impairments in reward processing to rats exposed to known depression risk factors of early life stress,[51] chronic treatment with a prodepressant drug or a known, prodepressant immune-based treatment, interferon alpha.[53]

  • In the affective bias test (ABT), rats experiencing chronic pain developed a positive affective bias after treatment with the atypical analgesic, gabapentin, relative to the sham controls. This suggests that gabapentin-induced antinociception induces a relatively more positive state possibly arising from remediation of a negative affective state resulting from chronic pain, but gabapentin itself does not modify affective state

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Summary

Introduction

Chronic pain is highly comorbid with affective disorders including major depressive disorder (MDD).[3,33] Despite this, it is not yet understood whether this comorbidity arises through overlapping neurobiology[63] or independent mechanisms.[6].

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