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Principal Investigator: BENEDICT J KOLBER
Organization: UNIVERSITY OF KENTUCKY
Fiscal Year: 2024
Award: $360,514
Funding agency: National Center for Complementary and Integrative Health
PROJECT SUMMARY/ABSTRACT
There is a pressing need to identify and validate new targets for chronic pain and new sources for novel
compounds. This proposal will use novel extracts and pure compounds from multiple Cameroonian plants
namely Paullinia pinnata, Petersianthus macrocarpus and Acacia sieberiana to probe the biology and therapeutic
potential of an exciting non-opioid target for pain, focusing on calcium homeostasis especially through sigma 2
(σ-2) (aka transmembrane protein 97 (TMEM97)). “Agonists” for σ-2/TMEM97 reduce neuropathic and
inflammatory pain in mice. Our primary research goal is to use a focused interdisciplinary approach to isolate
bioactive compounds from traditional medicine and utilize these new tools in Cameroon to address research and
education disparities that contribute to poor pain outcomes in Central Africa. This goal will be pursued with a
unique collaboration that we have developed between researchers at the University of Dschang (Cameroon; Dr.
Nguelefack), the University of Texas at Dallas (USA; Dr. Kolber) and the University of Kentucky (USA; Dr.
Tidgewell). Preliminarily, the Nguelefack lab has shown that crude extracts of P. Pinnata, P. macrocarpus and
A. sieberiana significantly decrease inflammatory and neuropathic pain in rats. The Tidgewell/Kolber groups
have shown that the methanol extracts of P. pinnata show in vitro binding affinity to σ-2/TMEM97 and modulate
primary sensory neurons. This proposal will utilize our interdisciplinary and international approach with in vitro
evaluation of plant extracts, followed by fractionation, in vitro testing of σ-2/TMEM97 binding, and additional in
vitro validation at UT Dallas and Dschang with pure compounds. In addition to the research focus on Ca2+
homeostasis, this proposal aims to build research and clinical capacity for the study of pain in Cameroon and
surrounding countries. This will be accomplished using a mixture of capacity building initiatives including the
training of Cameroon trainees in the US and Cameroon, the building of Dschang University as a center for pain
research in central Africa, and the hosting of local workshops at Dschang to support the spread of research
knowledge in Cameroon and surrounding countries.
Terms: <Acacia><Address><Afferent Neurons><Affinity><African><African Traditional Medicine><Agonist><Analgesic Agents><Analgesic Drugs><Analgesic Preparation><Analgesics><Animals><Anodynes><Antinociceptive Agents><Antinociceptive Drugs><Area><Assay><Autoregulation><Barbasco><Binding><Bioassay><Biological Assay><Biology><Blinded><Botanical medicine><Calcium><Cameroon><Carbinol><Cell Body><Cells><Central Africa><Chemical Fractionation><Chemistry><Clinical><Collaborations><Common Rat Strains><Complex Extracts><Computing Methodologies><Country><Crude Extracts><Development><Disparities><Disparity><Dorsal Root Ganglia><Dysfunction><Education><Educational aspects><Educational workshop><Elements><Europe><Evaluation><FRACN><Fluorescence><Fractionation><Fractionation Radiotherapy><Functional disorder><Goals><Homeostasis><Human><Human Resources><Image><In Vitro><Integral Membrane Protein><International><Intrinsic Membrane Protein><Investigators><Kentucky><Knowledge><Locust Tree><Lytotoxicity><Manpower><Mediating><Medicinal Plants><Membrane><Methanol><Methyl Alcohol><Mice><Mice Mammals><Microscopy><Modern Man><Modernization><Molecular><Molecular Interaction><Murine><Mus><Natural Products><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurosciences><Neurosciences Research><New Agents><Outcome><Pain><Pain Centers><Pain Clinics><Pain Relief Units><Pain Research><Painful><Paullinia pinnata><Peripheral><Peripheral Nervous System><Physiological Homeostasis><Physiology><Physiopathology><Phytochemical><Phytomedicines><Phytotherapeutics><Plant Extracts><Plants><Poison><Process><Psychoactive Agents><Psychoactive Compound><Psychoactive Drugs><Psychopharmaceuticals><Psychotropic Drugs><Rat><Rats Mammals><Rattus><Receptor Protein><Research><Research Infrastructure><Research Personnel><Research Resources><Researchers><Resources><Rodent><Rodentia><Rodents Mammals><Sensory><Sensory Neurons><Site><Source><Spinal Ganglia><Surface><Testing><Texas><Therapeutic><Toxic Chemical><Toxic Substance><Traditional Medicine><Training><Transmembrane Protein><Transmembrane Protein Gene><Triage><Universities><Validation><Wattle Tree><Wood Alcohol><Work><Workshop><alleviate symptom><ameliorating symptom><calcium metabolism><chronic neuropathic pain><chronic pain><complex extract><computational methodology><computational methods><computer based method><computer methods><computing method><cytotoxicity><decrease symptom><developmental><dorsal root ganglion><drug development><drug discovery><experiment><experimental research><experimental study><experiments><fewer symptoms><imaging><improved><in vitro Assay><in vitro testing><inflammatory pain><inhibit pain><innovate><innovation><innovative><interdisciplinary approach><interest><membrane structure><multidisciplinary approach><naturally occurring product><neuronal><neuropathic pain><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><non-narcotic analgesic><non-opiate analgesic><non-opioid><non-opioid analgesic><non-opioid therapeutics><nonnarcotic analgesics><nonopiate analgesic><nonopioid><nonopioid analgesics><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><pain inhibition><pain killer><pain medication><pain model><pain outcome><pain reduction><pain reliever><pain-related outcome><painful neuropathy><painkiller><pathophysiology><personnel><pharmacologic><plant compound><plant derived compound><receptor><reduce pain><reduce symptoms><relieves symptoms><screening><screening program><screenings><symptom alleviation><symptom reduction><symptom relief><targeted agent><therapeutic outcome><therapy outcome><tool><toxic compound><training opportunity><validations>