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Exploring the Role of Descending Dopamine Pain Modulation in the Transition to Chronic Pain
Abstract   Peer reviewed

Exploring the Role of Descending Dopamine Pain Modulation in the Transition to Chronic Pain

Angela F. Smith, Kazuhiro Hayashi, Adam J. Janowski, Ashley N. Plumb and Kathleen A. Sluka
The journal of pain, Vol.25(4 Supplement), pp.13-13
04/2024
DOI: 10.1016/j.jpain.2024.01.065

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Abstract

Changes in the central nervous system and descending pain modulation may underlie the transition to chronic pain, but our understanding of these changes is insufficient to predict and prevent the transition to chronic pain. The descending dopamine pain modulation system originates in the A11 nucleus of the hypothalamus and projects ipsilaterally to all levels of the spinal cord. A faciliatory role has been suggested for spinal dopamine in animals vulnerable to chronic pain from a prior inflammatory insult. We hypothesized that A11 neurons become active following peripheral insult to facilitate the transition to chronic pain via D1-like receptor mediated phosphorylation of NMDA receptors. Adult male and female C57BL6/J mice were used in this study. Pain was induced by two intramuscular injections (pH 4.0) five days apart in the left gastrocnemius muscle. To assess pain, muscle withdrawal thresholds (MWT) and paw sensitivity (vF) were assessed before and after induction of the model. We collected tissue or performed pharmacological manipulation at or near the time of the transition to chronic pain, following the second intramuscular injection, to test the role of A11 activity, D1-like receptors, and NMDA receptors in the transition to chronic pain. We found that in our model, D1-like receptor activity is necessary for the transition to chronic pain in male but not female mice, but D1-like receptor mRNA expression is not elevated following the transition to chronic pain. This suggests D1-like receptors may facilitate the transition to chronic pain in males via downstream signaling pathways. Funding: NIH AR073187, T32GM144636.

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