# Mechanistic studies on analgesic effects of terpene enriched extracts from hops

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $204,206

## Abstract

ABSTRACT
Chronic pain affects up to 1/5 of the world population. It is a debilitating health condition with significant socio-
economic costs. Management of chronic pain continues to present therapeutic hurdles, and the utility of opiate
analgesics has reached a plateau as more and more people have fallen victim to opiate addiction, contributing
to the opiate crisis. Plants of the Cannabaceae family, such as Cannabis sativa (cannabis) and Humulus
lupulus (hops), have a long history of traditional use in the mitigation of pain and inflammation, yet the
mechanistic basis for these activities and the identities of the compounds responsible are not well understood.
In the proposed work, we will take a multidisciplinary approach to investigate the analgesic effects of terpenes
from the Cannabaceae family. Rather than use cannabis, whose study and product market is complicated by
conflicting federal and state laws, we will focus on terpenes found in hops, which is a related species and
shares a very similar terpene profile. We will acquire botanically authenticated hops cones materials for
extraction by supercritical CO2 methods to create terpene enriched and depleted hops extracts for study,
enabling assessment of synergy between terpenes. We will also use individual terpene standards in our
proposed studies. Extracts will be chemically characterized by GC-MS and NMR and assessed for bioactivity
using in vitro models to assess the capacity to affect excitability and sensitization of cultured DRG nociceptive
neurons. We will analyze the ability of Hops extracts or candidate terpenes to modulate nociceptor TRPV1
sensitization by inflammatory stimuli using calcium imaging, and examine the capacity of terpenes to modulate
nociceptor excitability use whole cell patch clamp electrophysiology. PCA and Compound Activity Mapping
analyses on chemical features and bioactivities observed will guide selection of the most active constituents,
including consideration of synergistic combinations of terpenes. In the second part of our project, we will
assess the efficacy of the most promising hops terpene-enriched extracts or isolated terpenes to mitigate pain
and immune activation in animal models of inflammatory (CFA) and neuropathic (SNI) pain. Plasma and
tissues from mice will also be assessed for the levels of specific terpenes and their metabolites via a targeted
high-resolution metabolomics approach. In addition to behavioral analysis, we will analyze plantar and DRG
immune activation, as well as microglia and astrocyte activation in the spinal cord. This study is responsive to
the RFA-AT-19-009 objectives to 1) investigate the mechanisms by which terpenes may affect pain pathways,
including ascending and/or descending neural pathways, cellular and molecular signaling pathways,
neuroimmune interactions, or other innovative regulatory pathways related to pain; and to 2) explore analgesic
potential of terpenes for different pain modalities. This interdisciplinary...

## Key facts

- **NIH application ID:** 10018714
- **Project number:** 5R21AT010774-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Isaac Ming-Cheng Chiu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,206
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018714

## Citation

> US National Institutes of Health, RePORTER application 10018714, Mechanistic studies on analgesic effects of terpene enriched extracts from hops (5R21AT010774-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10018714. Licensed CC0.

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