R21AT013164

From traditional medicine to innovation: Discovering novel analgesics targeting calcium modulation from Cameroonian phytochemicals - 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.

University Of Kentucky Research Foundation

TO EVALUATE COMPLEMENTARY AND INTEGRATIVE HEALTH APPROACHES. THE FOLLOWING OBJECTIVES SUPPORT THIS GOAL: (1) COORDINATE AND FACILITATE THE INVESTIGATION OF COMPLEMENTARY AND INTEGRATIVE HEALTH APPROACHES THROUGH PEER-REVIEWED GRANT SOLICITATIONS, (2) INTERFACE WITH THE NCCIH NATIONAL ADVISORY COUNCIL, (3) CONDUCT TECHNOLOGY ASSESSMENT CONFERENCES FOR THE PURPOSE OF ESTABLISHING AREAS OF CLINICAL AND PRE-CLINICAL RESEARCH THAT NEED TO BE FURTHER DEVELOPED WITHIN COMPLEMENTARY HEALTH APPROACHES, AND (4) MAINTAIN A COMPREHENSIVE BIBLIOGRAPHIC DATA BASE IN CONJUNCTION WITH THE NATIONAL LIBRARY OF MEDICINE. THE NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH (NCCIH) REGULARLY EXAMINES AND REDEFINES ITS RESEARCH PRIORITIES. IN SETTING RESEARCH PRIORITIES, NCCIH CONSIDERS ITS EXISTING RESEARCH PORTFOLIO, ITS 5-YEAR STRATEGIC PLAN, THE RECOMMENDATIONS OF THE NATIONAL ADVISORY COUNCIL FOR COMPLEMENTARY AND INTEGRATIVE HEALTH, CURRENT SCIENTIFIC ADVANCES, THE PLANS OF OTHER NIH INSTITUTES AND CENTERS, AND INPUT FROM EXPERT PANELS AND STAKEHOLDERS. RESEARCH CONSTITUTING A RIGOROUS EVIDENCE BASE FOR COMPLEMENTARY HEALTH APPROACHES WILL BE DEVELOPED THROUGH A RANGE OF RESEARCH STRATEGIES INCLUDING BASIC AND TRANSLATIONAL RESEARCH, AND CLINICAL INVESTIGATION. PRIORITY SETTING ALSO TAKES INTO ACCOUNT: 1)SCIENTIFIC PROMISE, 2)AMENABILITY TO RIGOROUS SCIENTIFIC INQUIRY,3) POTENTIAL TO CHANGE HEALTH PRACTICES, AND 4) RELATIONSHIP TO USE AND PRACTICE. RESEARCH APPROACHES BASIC, TRANSLATIONAL, EFFICACY/EFFECTIVENESS, AND IMPLEMENTATION RESEARCH FOR COMPLEMENTARY AND INTEGRATIVE HEALTH APPROACHES NEED TO BE STUDIED ACROSS THE RESEARCH CONTINUUM. NCCIH CONTINUES TO EMPHASIZE BASIC RESEARCH THAT DEFINES BIOLOGICAL EFFECTS AND MECHANISMS OF ACTION, THIS RESEARCH IS AIMED AT UNDERSTANDING THE NATURE OF COMPLEMENTARY HEALTH APPROACHES SUCH AS THEIR BIOLOGY, PHYSIOLOGY, AND PHYSICAL, CHEMICAL AND BEHAVIORAL PROPERTIES. NCCIH ALSO SUPPORTS THE DEVELOPMENT OF TOOLS, MODELS, AND METHODOLOGIES FOR STUDYING THESE APPROACHES. NCCIH CONTINUES TO ENCOURAGE EFFICACY STUDIES TO DETERMINE SPECIFIC CLINICAL EFFECTS OF COMPLEMENTARY HEALTH APPROACHES UNDER CAREFULLY CONTROLLED CONDITIONS THAT MINIMIZE NONSPECIFIC AND CONTEXTUAL EFFECTS. THERE IS ALSO THE NEED TO STRENGTHEN TRANSLATIONAL AND PRELIMINARY CLINICAL RESEARCH REQUIRED TO DESIGN AND IMPLEMENT DEFINITIVE CLINICAL RESEARCH AND ""REAL WORLD"" OUTCOMES AND EFFECTIVENESS RESEARCH THAT CAPITALIZES ON THE REALITY THAT MANY COMPLEMENTARY HEALTH APPROACHES ARE IN WIDESPREAD PUBLIC USE. NCCIH'S SUPPORT OF TRANSLATIONAL RESEARCH ADDRESSES THE NEED FOR VALID, RELIABLE AND RELEVANT RESEARCH TOOLS, OUTCOME MEASURES, AND INNOVATIVE METHODOLOGY TO ENHANCE THE RIGOR OF COMPLEMENTARY HEALTH APPROACHES WITHIN CLINICAL STUDIES AND TO ENSURE THAT THEY ARE MAXIMALLY INFORMATIVE. NCCIH EMPHASIZES STUDIES THAT INFORM THE DESIGN OF FUTURE TRIALS SUCH AS THOSE THAT WILL: DEVELOP AND VALIDATE OUTCOME MEASURES, STANDARDIZE TREATMENT PROT

93.989 - International Research and Research Training

National Center for Complementary and Integrative Health (NCCIH) [HHS - NIH]

Fogarty International Center (FIC) [HHS - NIH]

Lexington, Kentucky 405360596 United States

Single Zip Code

Global Brain and Nervous System Disorders Research Across the Lifespan (R21 Clinical Trial Optional) (PAR-22-098)

Amendment Since initial award the total obligations have increased 7110% from $5,000 to $360,514.