Resiniferatoxin: Using Extreme "Heat" to Treat Pain

Introduction to Resiniferatoxin

At the 2nd Annual Future of Intrathecal Drug Delivery Conference (2012), I had the pleasure of hearing a lecture on the intraspinal administration of resiniferatoxin (RTX), a very potent analogue of capsaicin. Intrigued by the topic, I reached out to the speaker for further discussion. Our conversation delved into resiniferatoxin, pure capsaicin, and their origins in chili peppers.

Capsaicin and Its Derivatives

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

The Scoville Scale

In 1912, American Pharmacist Wilbur Scoville developed the Scoville Organoleptic Test, which measures capsaicinoid content. In this test, an alcohol extract of 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. For example, bell peppers have a rating of zero on the scale, while the hottest peppers, such as the Trinidad Scorpion Butch T and Trinidad Moruga Scorpion, have ratings between 1.4 million and 2 million Scovilles.

Capsaicin and RTX in Pharmaceuticals

In pharmaceuticals, the Scoville Scale has been applied to chemicals derived from pepper extracts used in topical pain management products. Pure capsaicin, a hydrophobic, colorless, odorless compound, has a rating of 16 million Scoville Units. Resiniferatoxin, however, reaches up to 16 billion Scovilles, making it 1,000 times "hotter" than pure capsaicin.

Mechanism of Action

The extreme "heat" of RTX relieves pain by activating the vanilloid receptor in a subpopulation of primary afferent sensory neurons involved in nociception (pain transmission). RTX binding opens the calcium channel, causing excessive activation. This prolonged calcium influx specifically deletes sensory neurons containing the TRPV receptor, resulting in permanent receptor removal, desensitization, and analgesia. A clinical study demonstrated significant pain relief in companion dogs with bone cancer through the intraspinal use of RTX.

High Performance Liquid Chromatography (HPLC)

Though Scoville units are still used today, the Scoville Organoleptic Test has been largely replaced by High Performance Liquid Chromatography (HPLC) for pharmaceuticals. HPLC is the most accurate method for measuring chemical compound concentrations. In this procedure, chili pods are dried and ground, the pungent chemicals are extracted, and the extract is analyzed using an HPLC device. This method, while more costly than the Scoville test, offers much greater accuracy.

Hartley Medical's Commitment to Quality

Hartley Medical endorses HPLC testing for quality control. Utilizing advanced testing, we quantify milligrams per unit volume, ensure the accuracy of final product compounding, and determine exact levels of compounded pharmaceutical preparations with a precision of plus or minus 2 to 5 percent. This cutting-edge technology advances quantitative analytical chemistry, ensuring the highest standards in our products.