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Correlation Between Ventral Striatal Catecholamine Content and Nociceptive Thresholds in Neuropathic Mice

  • Anna M.W. Taylor
    Affiliations
    Department of Anesthesiology and Perioperative Medicine, University of California, Irvine, California

    Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California
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  • Niall P. Murphy
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California
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  • Christopher J. Evans
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California
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  • Catherine M. Cahill
    Correspondence
    Address reprint requests to Catherine M. Cahill, PhD, Department of Anesthesiology and Perioperative Medicine, University of California, 2117 Gillespie Neuroscience Research Facility, 837 Health Sciences Rd, Irvine, CA 92697.
    Affiliations
    Department of Anesthesiology and Perioperative Medicine, University of California, Irvine, California
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      Highlights

      • Neuropathic pain resulted in loss dopamine and rise in norepinephrine content in the ventral striatum.
      • Pain thresholds no longer correlated with ventral striatal dopamine content in neuropathic pain.
      • Ventral striatal norepinephrine content correlated with pain thresholds only in neuropathic pain.
      • These results point to a dramatic change in striatal catecholamine signaling in neuropathic pain.

      Abstract

      Neuropathic pain is characterized by persistent, intractable pain following damage or dysfunction of the nervous system. Analgesics that include central, rather than purely peripheral, targets are more effective when treating neuropathic pain, highlighting the spinal and/or supraspinal mechanisms that contribute to this aberrant pain condition. The striatum represents one of the brain regions that have been implicated in pain processing. Release of dopamine in the ventral striatum is normally associated with analgesia. Clinical and human imaging studies suggest that dopamine is disrupted in neuropathic pain patients, although the conclusions drawn from these studies are limited by their noninvasive imaging or pharmacologic approaches. In this study, we used a C57Bl/6 mouse model of neuropathic pain to describe the changes in neurotransmitter content in the striatum and their relationship to evoked pain thresholds. Striatal dopamine content negatively correlated with mechanical thresholds in sham animals. Neuropathic pain animals had reduced dopamine content that was not correlated with mechanical thresholds. In contrast, norepinephrine content was significantly increased and correlated with mechanical thresholds in neuropathic, but not sham, animals. These results describe changes in striatal signaling in neuropathic pain animals and contribute to the literature defining the role of dopamine and norepinephrine in mediating sensory thresholds in healthy and neuropathic pain states.

      Perspective

      Results show significant loss of ventral striatal dopamine in neuropathic pain conditions, and the relationship of ventral striatal catecholamines to pain thresholds is changed in neuropathic pain. These results complement human imaging studies and provide evidence that chronic pain alters the function of reward systems.

      Key words

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