Evaluating ghost pipe (monotropa uniflora) as a potential source of novel analgesic compounds

The National Center for Complementary and Integrative Health, part of the Department of Health and Human Services National Institutes of Health, awarded The Pennsylvania State University $145,520 on October 3, 2025, under the Research and Training in Complementary and Integrative Health program (CFDA 93.213).

The award funds research to identify novel analgesic compounds from ghost pipe (Monotropa uniflora), a North American medicinal plant historically used for pain management. The project involves chemical profiling of ghost pipe extracts and fractions to establish a metabolomic baseline, evaluation of binding affinity to human neuro-receptors via radioligand binding assay, construction of a biochemometric model to identify receptor-binding compounds, assessment of anti-inflammatory activity in in vitro systems, and testing of analgesic effects in murine in vivo models. Active compounds will be isolated and characterized using high-resolution mass spectrometry and nuclear magnetic resonresonance.

Performance is located in State College, Pennsylvania. The period of performance extends from the award date through July 31, 2027. This is a project grant providing research training in pharmacognosy and analgesic screening methods to support the development of pain management alternatives to opioid pharmaceuticals and surgical interventions.

Abstract

Chronic pain is one of the most common reasons for seeking medical care, affecting 50 million americans. While often treated with opioid pharmaceutical or surgical interventions, complementary traditional health approaches to pain management may offer safer, more effective, and cost-efficient options. Ghost pipe (monotropa uniflora, ericaceae) is a north american medicinal plant that has been used historically for its analgesic effects and is still popular today. Yet, there are zero modern publications on either the phytochemistry or efficacy of the plant. Based upon our extensive survey of ghost pipe consumers, and preliminary data suggesting pain response modulation in a murine model, i hypothesize that ghost pipe is a botanical analgesic capable of exerting effects on neurological and analgesic responses via novel bioactive compounds. This proposal provides novel research training in pharmacognosy and analgesic screening methods to identify compounds from ghost pipe that modulate pain. Ghost pipe extracts and fractions will be chemically profiled to provide a metabolomic baseline and insight into the chemical diversity of this plant. They will be evaluated for their binding affinity for a panel of human neuro-receptors in a radioligand binding assay, after which a biochemometric model will be constructed to deduce which compounds are primarily responsible for the receptor binding. In addition, the ghost pipe extracts and fractions will be examined in in vitro systems to establish anti-inflammatory activity, as well as a murine in vivo models to determine potential analgesic effects. The bioassay data will be concatenated with the metabolomic profiling to identify the compounds responsible for observed activity. Active compounds will be isolated and characterized using high-resolution mass spectrometry (hrms) and nuclear magnetic resonance (NMR). This research sets the stage for future in-depth mechanistic studies and assaying the addictive potential of ghost pipe metabolites. This will advance the understanding and characterization of herbal analgesics, while the experimental design experience, collection of data, development of phytochemical interventions, and professional development activities described herein will result in the development of a well-rounded, independent researcher.