Researchers investigate potential use of plant as a pain killer
Washington, DC -- Researchers at the National Institutes of Health have enlisted one of the oldest known medicinal plants as a potent painkiller. Euphorbia resinfera, a cactus-like plant, is a member of the euphorb family, of which there about 2000 species. The active ingredient, resiniferatoxin, was isolated in the 1970s. It is a potent analogue of capsaicin, the substance that gives chilli peppers their pungency.
The work is a novel approach to pain management because it elliminates nerve cells involved in chronic pain but does not damage other nerve cells. Opioid analgesics, currently the main tool for treating moderate to severe chronic pain, do not provide relief in all cases.
“We need something better,” said Michael Iadarola speaking at a workshop in new advances in pain control held at the National Institutes of Health. A few years ago Dr Iadarola and his associates at the National Institute of Dental and Craniofacial Research found that resiniferatoxin can disable and ultimately kill the neurones that convey to the nervous system sensations of heat and inflammation. It does this by binding to a protein called vanilloid receptor 1 that is present on the surface of certain types of heat-pain sensing neurones. Resiniferatoxin attaches to the receptor and prompts an influx of calcium but only by those cells that manufacture the ion channel.
Nerve cells in the peripheral nervous system transmit their signals to the spine, where they are processed and then routed to the brain. They bundle in dorsal root ganglia near the spine. The researchers argued that if resiniferatoxin was applied directly to the ganglia this would selectively delete the neurones such as C fibres that have large amounts of vanilloid protein on their surface and so shut off the chronic pain signals in conditions such as severe arthritis, peripheral neuromas, and advanced cancer.
This indeed proved to be the case. In two studies in pet dogs affected by osteosarcoma, osteoarthritis, or both, and treated intrathecally with resiniferatoxin, the animals became more active and walked with no sign of limps. None had any side effects from their treatment. The dogs’ temperaments improved and the need for other pain controlling medications was eliminated or greatly reduced.
Dr Iadarola describes the technique as a molecular scalpel. “It deletes certain neurones but leaves others untouched. So the nervous system functions normally. A spectrum of pain responsiveness has been deleted.” The results are sufficiently promising that the investigators are now planning a clinical study on terminally ill patients with osteosarcoma.
BMJ 2005;331:1104 (12 November).
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