Abstract
106 - Exploring the Role of Descending Dopamine Pain Modulation in the Transition to Chronic Pain
The journal of pain, Vol.29(Supplement), 104902
04/2025
DOI: 10.1016/j.jpain.2025.104902
Abstract
Descending pain modulation systems are key targets in understanding the transition to chronic pain. The descending dopamine pain modulation system originates in the A11 nucleus of the hypothalamus and projects ipsilaterally to the spinal cord. Very little is known about the activity and properties of A11 dopamine neurons in the context of chronic pain. However, in animals with an inflammatory hyperalgesic priming model, spinal dopamine and dopamine D1-like receptors have been implicated in the transition to chronic pain. We hypothesize that A11 neurons are active in the transition to chronic pain, releasing dopamine in the spinal cord and facilitating hyperalgesia via D1-like receptor mediated phosphorylation of NMDA receptors. In male and female C57 mice we used a noninflammatory hyperalgesic priming model consisting of two spaced injections of acidic saline; the first injection is a priming stimulus, while the second injection initiates a transition to chronic pain. We collected brain and spinal cord tissue from animals with and without pain to characterize A11 dopamine neurons and spinal dopamine in the context of chronic pain. We also evaluated the effect of pharmacological manipulation of spinal D1-like receptors during the transition to chronic pain. We found that in this model, spinal D1-like receptor blockade delays the onset of hyperalgesia in male but not female mice. Additional experiments will characterize the activity and properties of A11 dopamine neurons, the source of spinal dopamine. Future directions will explore if spinal D1-like receptor activation mediates phosphorylation of NMDA receptors.
Details
- Title: Subtitle
- 106 - Exploring the Role of Descending Dopamine Pain Modulation in the Transition to Chronic Pain
- Creators
- Angela Smith - University of IowaElizabeth Gross - University of IowaKazuhiro Hayashi - University of IowaAdam Janowski - University of IowaStephanie Gantz - University of IowaKathleen Sluka - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The journal of pain, Vol.29(Supplement), 104902
- DOI
- 10.1016/j.jpain.2025.104902
- ISSN
- 1526-5900
- eISSN
- 1528-8447
- Publisher
- Elsevier Inc; EDINBURGH
- Language
- English
- Date published
- 04/2025
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
- Record Identifier
- 9984820572602771
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