# Evaluation of peripheral cannabinoid receptors as a target for pain management

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2021 · $66,390

## Abstract

ABSTRACT
Chronic pain impacts 11.2% of the U.S. population, and leads to considerable disability. Current
pharmacotherapies for chronic pain are largely ineffective and rely heavily on opioids. Over-prescription of
opioid-based compounds for pain disorders has contributed to an opioid overdose epidemic in the U.S.,
highlighting the urgent need to develop safer and more effective therapeutics for pain. The endocannabinoid
system, which consists of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, has emerged
as an alternative therapeutic target to currently available pain medications. Exogenously administered
cannabinoids (CBs) display mixed outcomes in clinical trials for chronic pain suggesting the therapeutic
potential of CB-based therapies in pain disorders is largely unknown. CB agonists also exhibit unwanted side-
effects (e.g. tolerance and psychoactivity) largely due to central CB1R activation. Dorsal root ganglion (DRG)
contain the cell bodies of primary afferents responsible transmitting peripheral nociceptive signaling to the
spinal cord. Activation of peripheral CB1R receptors in DRG has been viewed as a potential means to harness
the therapeutic actions of CB1Rs while circumventing unwanted CNS-related side-effects. Yet, there have been
few investigations regarding antinociceptive effects of peripheral CB ligands. In the present proposal I plan to
incorporate pharmacological and novel genetic-based approaches to elucidate the contributions of peripheral
CB1R receptors in reducing sensory and non-reflexive components of pain in both male and female mice. The
mentor's lab previously demonstrated functional differences of metabotropic glutamate receptor 2/3 receptors
activity in cultured neurons derived from mouse and human dorsal root ganglion. This suggests the
mechanistic basis of other pharmacological targets, such as CBs, may differ between species. Human and
mouse CB1 exhibit differential signaling in hippocampal autaptic cultures. Only one report to-date investigated
CB signaling in human-derived DRG and no comparative studies regarding CB receptor signaling have ever
been conducted between rodent and human in this tissue. To better understand the clinical validity of targeting
peripheral CB1Rs I will take advantage of an extremely unique opportunity to conduct comparative studies of
CB receptor function in mouse and human DRG. These studies have potential to generate transformative data
in understanding transability of preclinical findings regarding peripheral antinociceptive effects of CBs. The
central hypothesis that CB1R present on nociceptors in DRG are responsible for the antinociceptive effects of
peripheral CB administration observed in mice and that this mechanism will translate to humans will be
evaluated in the present proposal. The data generated from the proposed experiments will greatly aid in our
understanding of the underlying mechanisms in which peripheral CB1R activation promotes antinociceptive l...

## Key facts

- **NIH application ID:** 10294223
- **Project number:** 5F32DA051160-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Richard Slivicki
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294223

## Citation

> US National Institutes of Health, RePORTER application 10294223, Evaluation of peripheral cannabinoid receptors as a target for pain management (5F32DA051160-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10294223. Licensed CC0.

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