Researchers investigate potential use of plant as a pain killer
BMJ 2005; 331 doi: http://dx.doi.org/10.1136/bmj.331.7525.1104-c (Published 10 November 2005) Cite this as: BMJ 2005;331:1104- Charles Marwick
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
