CHILI PEPPERS--A REVOLUTIONARY NEW INJECTABLE TREATMENT FOR PAIN

Despite enormous investments by industry, surgical pain management has changed little since the first successful demonstration of ether general anesthesia at MGH in 1846. These work by interfering with the excitability of all neurons, not just pain-sensing ones. Thus, these drugs produce dramatic side effects, such as loss of consciousness in the case of general anesthetics or temporary paralysis for local anesthetics. Childbirth, surgery, and trips to the dentist might be less traumatic in the future, thanks to researchers at Massachusetts General Hospital and Harvard Medical School who have succeeded in selectively blocking pain-sensing neurons in rats without interfering with other types of neurons.

The new method exploits a membrane-spanning protein called TRPV1, which is unique to pain-sensing neurons. TRPV1 forms a large channel, where molecules can enter and exit the cell. But a “gate” typically blocks this opening. The gate opens when cells are exposed to heat or the chili-pepper ingredient capsaicin. Thus, bathing pain-sensing neurons in capsaicin leaves these channels open, but non-pain sensing neurons are unaffected because they do not possess TRPV1. The new work builds on research conducted since the 1970s showing how electrical signaling in the nervous system depends on the properties of ion channels, that is, proteins that make pores in the membranes of neurons. This new method then takes advantage of a special property of the lidocaine derivative QX-314. Unlike most local anesthetics, QX-314 can’t penetrate cell membranes to block the excitability of the cell, so it typically lingers outside neurons where it can’t affect them. For this reason it is not used clinically.

When pain-sensing neurons are exposed to capsaicin, however, and the gates guarding the TRPV1 channels disappear, QX-314 can enter the cells and shut them down. But the drug remains outside other types of neurons that do not contain these channels. As a result, these cells fully retain their ability to send and receive signals. Eventually, this method could completely transform surgical and post-surgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis. In fact, the possibilities seem endless. We could even imagine using this method to treat itching, as itch-sensitive neurons fall into the same group as pain-sensing ones.