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. This proposal will use novel extracts and pure compounds from multiple Cameroonian plants,like Paullinia pinnata, to probe the biology and therapeutic potential of an exciting non-opioid target for pain, Sigma 2 (aka transmembrane protein 97 (Tmem97)). This project will focus on examining the impact of these phytoichemicals on Ca+2 homeosotasis within DRG neurons, specifically via the Sigma 2 receptor. Agonists for Sigma2/Tmem97 reduce neuropathic pain in male mice. As a protein that is found in both dorsal root ganglia (DRG) and central nervous system (CNS) neurons, our primary research goal is the study and validation of Sigma2/Tmem97 in neuropathic pain. 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 (i.e. aqueous and methanol) of P. pinnata significantly decrease arthritis-like pain and inflammation in rats. The Tidgewell/Kolber groups have shown that the methanol extracts show in vitro binding affinity to Sigma2/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 Sigma2/Tmem97 binding, and additional in vitro validation at UT Dallas and Dschang with pure compounds. In addition to the research focus on Sigma2/Tmem97, this proposal also aims to build research and clinical capacity for pain in Cameroon and surrounding countries. This will be accomplished using a mixture of capacity building initiatives including the training of Cameroon Post-docs in the US and Cameroon, the building of Dschang University as a center for pain research in central Africa, and the hosting workshops at Dschang to support the spread of research knowledge in Cameroon and surrounding countries.