Pain relief hinges on killing cells

Practitioners might soon rely on a new procedure to alleviate severe chronic pain resulting from cancer, osteoarthritis or surgery. Resiniferatoxin (RTX), first isolated in the 1970s, has been administered during a series of clinical studies to kill specific nerve cells while leaving others untouched.

The procedure works when the potent agonist RTX is injected to neuronal perikarya, which induces calcium cytotoxicity and selectively ablates nociceptive neurons. The RTX intervention removes the C-fiber line of communication but is not equivalent to drugs that block one of the multiple neuroactive substances that these neurons release or respond to.

"We think this approach has great utility in the veterinary setting," says Dr. Michael Iadarola, senior author and National Institutes of Heath researcher. "This procedure requires one treatment; you apply it once, and it lasts forever because the cells do not regenerate."

No side effects or abnormal scratching occurred at the injection sites, he says.

Clinical coup

Thus far, the treatment is understood to block experimental inflammatory hyperalgesia and neurogenic inflammation in rats and mitigates naturally occurring cancer pain and arthritic pain in dogs. Sensations of touch, heat and movement remained intact in both species, according to the study, commissioned by the National Institute of Dental and Craniofacial Research, a branch of NIH. The University of Pennsylvania's veterinary school also played a role in the work, which was published May 1 in the Journal of Clinical Investigation.

"It was very gratifying that we realized the therapeutic response, but we also were able to view the disposition and quality-of-life issues in the dogs in a way that was not possible in the rats," Iadarola says. "It restored their function."

All eight dogs later walked with little or no limp; temperaments improved, and the need for other pain-controlling medication was eliminated or greatly reduced, according to the report.

"We were looking for something that worked rapidly, and this procedure works in about 40 minutes," Iadarola says. "We're planning to work on a more formal, phase-one trial, and our goal is to manufacture a drug related to this find."

Afferon Corp., a U.S. pharmaceutical company, currently owns the rights to RTX, which the company markets to treat urinary incontinence in humans.

Researchers are optimistic about the treatment's practicality and effectiveness, and the report indicates that the RTX treatment could improve the way practitioners treat severe chronic pain.

"The data presented here suggests that cellular excision by molecular neurosurgery would confer several advantages over neurosurgical, chemical or radiofrequency neuroablative techniques in terms of selectivity, efficacy and lack of side effects," the report says. "RTX removes one class of neurons, whereas the other treatments lack sensor modality selectivity, and if motor axons are compromised, bring about loss of muscular control. Conventional ablative approaches often yield incomplete relief or evolve into a deafferentation pain syndrome."

The full report can be read online at http://www.nidr.nih.gov