The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain
- 1Washington University in St. Louis
Abstract
Descending projections from the brain to the spinal cord can regulate painful stimulus processing and are modulated by endogenous and exogenous opioids. We investigated the role of mu opioid receptors (MORs) in GABAergic vs. glutamatergic neurons of the rostral ventral medulla (RVM) in a mouse model of chronic neuropathic pain. We found that activating glutamatergic and GABAergic neurons in the RVM both result in antinociception [BC1.1]at baseline, but glutamatergic neurons enhance pain responses after nerve injury. [BC2.1]We then interrogated the role of RVM MOR signaling on neuropathic pain by using CRISPR/Cas9 to delete MOR in glutamatergic or GABAergic RVM neurons. We found that MOR knockout in glutamatergic and GABAergic RVM neurons precipitates early neuropathic pain onset with no effect on chronic pain intensity. These results suggest that RVM MOR signaling modulates hypersensitivity in the early phase of injury, but chronic neuropathic pain is largely independent of mu opioid receptor signaling.
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BibTeX
@misc{moffa2026role,
title = {{The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain}},
author = {J. C. Moffa and A. Gao and V. Kalyanaraman and M. Heitmeier and B. A. Copits},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.26.747135},
url = {https://www.biorxiv.org/content/10.64898/2026.08.26.747135v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - The role of mu opioid receptors on excitatory and inhibitory neurons in the rostral ventromedial medulla in neuropathic pain
AU - J. C. Moffa
AU - A. Gao
AU - V. Kalyanaraman
AU - M. Heitmeier
AU - B. A. Copits
PY - 2026
DA - 2026/08/26
PB - bioRxiv
DO - 10.64898/2026.08.26.747135
UR - https://www.biorxiv.org/content/10.64898/2026.08.26.747135v1
AB - Descending projections from the brain to the spinal cord can regulate painful stimulus processing and are modulated by endogenous and exogenous opioids. We investigated the role of mu opioid receptors (MORs) in GABAergic vs. glutamatergic neurons of the rostral ventral medulla (RVM) in a mouse model of chronic neuropathic pain. We found that activating glutamatergic and GABAergic neurons in the RVM both result in antinociception [BC1.1]at baseline, but glutamatergic neurons enhance pain responses after nerve injury. [BC2.1]We then interrogated the role of RVM MOR signaling on neuropathic pain by using CRISPR/Cas9 to delete MOR in glutamatergic or GABAergic RVM neurons. We found that MOR knockout in glutamatergic and GABAergic RVM neurons precipitates early neuropathic pain onset with no effect on chronic pain intensity. These results suggest that RVM MOR signaling modulates hypersensitivity in the early phase of injury, but chronic neuropathic pain is largely independent of mu opioid receptor signaling.
ER -