# Treatment of cancer pain by lipid mediator Resolvin D1: role of Prostaglandin and Endocannabinoid signaling

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $422,825

## Abstract

Pain associated with primary and metastatic bone tumors is often severe and difficult to manage. Opioids are
first-line treatment for severe cancer pain, but their side effects, including tolerance, addiction and respiratory
depression, limit their use. The search for opioid alternatives with high analgesic efficacy and low adverse
effects has yielded limited success. Long-term goal is to identify novel, effective, and safe alternatives to
opioids for pain treatment. This project is focused on Resolvin D1 (RvD1), an endogenous derivative of -3
polyunsaturated fatty acids, as a possible therapeutic for cancer pain. Using a mouse model of bone cancer
pain. Preliminary data show that systemic administration of RvD1 decreased cancer-evoked hyperalgesia,
attenuated sensitization of nociceptors and nociceptive dorsal horn neurons, and reduced descending
facilitation while increasing descending inhibition of nociceptive transmission from the rostral ventromedial
medulla (RVM). RvD1 did not impair motor function and did not produce place preference, suggesting it is not
addictive. The overall objective in this proposal is to determine peripheral and central underlying mechanisms
of RvD1 exerts analgesia. The central hypothesis is that systemic administration of RvD1 inhibits enzymes
involved in the biosynthesis of pronociceptive prostaglandins (PGs) and the hydrolysis of antinociceptive
endocannabinoids (eCBs) that reduce sensitization of nociceptive neurons and inhibit descending facilitation.
Preliminary data suggest that increased PGs and decreased eCBs in the DRG, spinal cord and RVM
contribute to neuronal sensitization and pain during cancer. Because RvD1 increased eCBs, role of different
types of cannabinoid receptors in RvD1 produced antinociception will be elucidated. The central hypothesis will
be tested in three specific aims. 1) Identify molecular mechanisms of RvD1 antinociception in the peripheral
and central nervous system; 2) Determine functional effects of RvD1 on nociceptive primary afferent and spinal
neurons during cancer-induced bone pain; and 3) Determine functional effects of RvD1 on descending
facilitation and inhibition from the RVM. For the first aim biochemical and molecular approaches will be used to
determine changes in prostaglandin and endocannabinoid signaling during the development of cancer- pain
and the effects of Resolvin D1. The second aim will investigate the effects of Resolvin D1 on sensitization of
nociceptors and dorsal horn neurons using in vivo electrophysiological and in vitro [Ca2+]i-imaging
approaches. The third aim will evaluate the effects of RvD1 on descending facilitation and inhibition by
determining if RvD1 reduces activity of ON cells and increases activity of OFF cells in the RVM and how it
affect nociceptive transmission in spinal dorsal horn neurons. The proposed research is innovative because it
will uncover novel mechanisms by which RvD1 reduces cancer pain. This project is significant because it...

## Key facts

- **NIH application ID:** 10894859
- **Project number:** 5R01CA263777-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sergey G Khasabov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $422,825
- **Award type:** 5
- **Project period:** 2021-08-05 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894859

## Citation

> US National Institutes of Health, RePORTER application 10894859, Treatment of cancer pain by lipid mediator Resolvin D1: role of Prostaglandin and Endocannabinoid signaling (5R01CA263777-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894859. Licensed CC0.

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