Kindai University reveals the mechanism behind analgesic effect of organic germanium, a health supplement: Expectations for use as drugs for intractable pain

The research group of Professor Atsufumi Kawabata, Associate Professor Fumiko Sekiguchi, and Lecturer Maho Tsubota of the Laboratory of Pharmacology and Pathophysiology, Division of Pharmacology & Pathophysiology, Faculty of Pharmacy, Kindai University, along with Professor Genzoh Tanabe of the Laboratory of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Kindai University, Yasuhiro Shimada and Takashi Nakamura of Asai Germanium Research Institute Co., Ltd., and Professor Hiroaki Yamaguchi of the Faculty of Medicine, Yamagata University, has shown that organic germanium, which is commercially available as a health supplement, has an analgesic (pain‐reliving) effect from trapping and inhibiting sulfide, which has the effect of stimulating sensory nerves in vivo.

According to Professor Kawabata, "More than 10 years ago, it was shown that sulfides produced in vivo are involved in the onset of intractable pain that doesn't respond to morphine. Then, a few years ago, we received a request from Asai Germanium Research Institute to clarify the action mechanism for germanium, which works well for pain, which was the impetus for starting our research."

The research group first used structural analysis to show that organogermanium hydrolyzates (THGP: a decomposition product obtained via the compound's reaction with water) react with sulfides to produce a reaction product that incorporates sulfur. In addition, electrophysiological studies demonstrated that THGP inhibits sulfide‐induced increases in the activity of T‐type calcium channels. From this, the research group found that the hydrolyzed organogermanium traps sulfides and suppresses increased activity by T‐type calcium channels. Furthermore, the research group revealed that, in mice, THGP showed a strong inhibitory effect on pain caused by sulfide injections and on visceral pain associated with cystitis and pancreatitis, which is caused by excessive sulfide production in the body.

These research results have revealed that hydrolyzed organogermanium suppresses a variety of pain types that are caused by increased T‐type calcium channel activity from sulfides, suggesting that they may be useful as a therapeutic agent for intractable pain.

Professor Kawabata said, "Currently, we are investigating the preventive and therapeutic effects of organic germanium on pain caused by the side effects of anticancer drugs, for which there are no effective treatments."

■ Sulfides: A general term for sulfur compounds that have a sulfur atom with the lowest oxidation number of ‐2. In an aqueous solution, they hydrolyze and exist as hydrogen sulfide ions, HS^‐.

■ T‐type calcium channel: One of the pathways in the cell membrane through which calcium ions existing outside the cell flow into the cell. When there is a slight rise in the cell membrane's potential (voltage), the channel opens and excites nerve cells.

Journal Information
Publication: Redox Biology
Title: A hydrolysate of poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) suppresses Ca_v3.2-dependent pain by sequestering exogenous and endogenous sulfide
DOI: 10.1016/j.redox.2022.102579