Cactus-Like Plant Shows Promise as Treatment for Intractable Cancer Pain

By Pat Anson

Throughout history, humans have often turned to plants and herbs for pain relief. Poppy plants gave us opium, aspirin was derived from willow trees, and peppermint oil is used to relieve everything from migraines to joint pain. Turmeric, ginger, lavender, eucalyptus and capsaicin are staples in many topical analgesics.

Researchers at the National Institutes of Health (NIH) say a cactus-like shrub native to Morocco also shows promise as a treatment for severe cancer pain and other types of intractable pain.

In a small pilot study recently published in the journal NEJM Evidence, they reported that injections of resiniferatoxin (RTX), a molecule derived from resin spurge (Euphorbia resinifera), provided durable pain relief to patients with terminal end-stage cancer.

"The effects are immediate," lead author Andrew Mannes, MD, chief of the NIH Clinical Center Department of Perioperative Medicine, said in a press release. "This is a potential new therapy from a new family of drugs that gives people with severe cancer pain an opportunity to return some normality to their lives."

The study involved 19 patients with terminal end-stage cancer who did not get adequate pain relief from opioids and other pharmaceutical drugs. But after a single injection of RTX, their worst pain intensity fell by 38% and their use of opioids by 57%. Quality of life also improved, allowing the patients to reengage with family and friends in their final days.

NIH scientists believe RTX has the potential to treat other pain conditions, including other types of cancer pain, neuropathy, post-surgical pain, trigeminal neuralgia, and chronic nerve pain caused by chemotherapy.

"Targeting specific nerves brings many pain disorders into the range of RTX and allows physicians to tailor the treatment to the patient's pain problem. This interventional approach is a simple path to personalized pain medicine," said senior author Michael Iadarola, PhD, a research scientist in the NIH Clinical Center Department of Perioperative Medicine.

RTX acts similarly to capsaicin, the active molecule in chili pepper, by numbing nerve fibers in damaged tissue and blocking them from sending pain signals to the brain. RTX enters the TRPV1 ion channel in the peripheral nervous system, allowing an overload of calcium to flood into the nerve fiber. Patients are still able to feel mild sensations like touch, pressure and pin pricks, but more severe pain signals are blocked.

"Basically, RTX cuts the pain-specific wires connecting the body to the spinal cord, but leaves many other sensations intact," Iadarola said. "These TRPV1 neurons are really the most important population of neurons that you want to target for effective pain relief."

"What makes this unique from all the other things that are out there is that it is so highly selective," Mannes said. "The only thing it seems to take out is heat sensation and pain."

People in North Africa knew this thousands of years ago. The first written record of Euphorbia resinifera being used for pain control dates back to the time of the Roman Emperor Augustus, when dried latex from the plant was used as medicine.

The NIH is planning further studies of RTX in clinical trials.