Knowledge Center

Resiniferatoxin: Using Extreme “Heat” to Treat Pain

by William Stuart

At the 2nd Annual Future of Intrathecal Drug Delivery Conference (2012), I had the pleasure of hearing a lecture by Dr. Tony Yaksh regarding the intraspinal administration of resiniferatoxin (RTX) – a very potent analogue of capsaicin. I was introduced to the topic about seven years ago, and I wanted to learn more – so after the conference I reached out to the doctor. We had an intriguing conversation regarding resiniferatoxin, pure capsaicin, and chili peppers.

Capsaicin is an ingredient used in topical preparations for pain management; what is interesting about capsaicin is that it is the active component of chili peppers. Being an irritant to humans by causing a burning sensation in any tissue it touches, capsaicin works by depleting or interfering with Substance P, a chemical involved in transmitting pain impulses to the brain. RTX, which is derived from the Euphorbia resinifera plant, is similar as it interacts with a TRPV-1 receptor in afferent nerves to produce prolonged analgesia.

In 1912, American Pharmacist Wilbur Scoville developed the Scoville Organoleptic Test – an assessment that made it possible to directly measure capsaicinoid content. In Scoville’s test, an alcohol extract of the capsaicin oil from a measured quantity of dried pepper is incrementally added to a solution of sugar water until the piquance (spice “heat”) is detectable by a panel of tasters. The degree of dilution determines the rating on the Scoville scale. Bell peppers, for example, contain no capsaicin and have a rating of zero on the scale – meaning there is no “heat” detectable, while the hottest peppers of the world, the Trinidad Scorpian Butch T and Trinidad Moruga Scorpion, have Scoville ratings between 1.4 million and 2 million Scovilles.

In the world of pharmaceuticals, the Scoville Scale means more than just an eye-watering, mouth-burning, smoke-coming-out-of-the-ear pepper. This rating system has been applied to chemicals derived from pepper extracts as well – extracts that are used in topical pharmaceuticals for pain management. Pure Capsaicin – which is a hydrophobic, colorless, odorless, crystalline to waxy compound – has a rating of 16 million Scoville Units . . . eight times the “heat” of the world’s hottest chili pepper. Resiniferatoxin, however, reaches up to 16 billion Scovilles – 1,000 times “hotter” than pure capsaicin.

The extreme “heat” of RTX works to relieve pain by activating the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (the transmission of physiological pain). RTX binding opens the calcium channel causing excessive activation. This prolonged calcium influx specifically deletes sensory neurons that contain the TRPV receptor – evoking a permanent removal of the receptor potential followed by desensitization and resulting in analgesia. Dr. Yaksh mentioned a clinical study conducted by Dorothy C. Brown, DVM, et al. that demonstrated significant pain relief in companion dogs diagnosed with bone cancer through the intraspinal use of RTX.

Though Scoville units are still used today, for pharmaceuticals the Scoville Organoleptic Test has been widely replaced by the use of High Performance Liquid Chromatography (HPLC) – the most accurate method for measuring concentrations of chemical compounds. In this procedure, chili pods are dried and then ground, the chemicals responsible for the pungency are extracted, and the extract is injected into the HPLC device for analysis. This method is more costly than the Scoville test, but much more accurate.

Hartley Medical endorses HPLC testing as we use it for quality control. Utilizing this type of advanced testing, we are able to quantify such things as the number of milligrams per unit of volume,  the accuracy of final compounding of products for patient administration, and  the exact levels of compounded pharmaceutical preparations – and not to the standard plus or minus 10%, but plus or minus 2 to 5%, etc. It is always fascinating to learn more about how this cutting-edge technology is used to advance quantitative analytical chemistry. For more information on HPLC, visit our blog entry entitled HPLC – Our Latest Example Of Leadership In Quality Assurance.

For more drug reviews, visit Hartley Medical’s Knowledge Center by clicking here.