Capsaicin, the active ingredient in chilli peppers, has been combined with QX-314, the normally inactive derivative of the local anaesthetic lidocaine, and has been found to selectively block pain-sensing neurons in rats without interfering with other types of neurons, such as motor neurons. The pain relief market is currently worth $25bn-plus (€17.7bn) and the researchers at Harvard Medical School and Massachusetts General Hospital believe childbirth, surgery and trips to the dentist could be less traumatic in the future as a result of their findings. "We've introduced a local anaesthetic selectively into specific populations of neurons. Now we can block the activity of pain-sensing neurons without disrupting other kinds of neurons that control movements or non-painful sensations," Harvard Medical School Professor Bruce Bean, an author on the paper that appears in Nature on October 4, said. Most surgical pain management using general and local anaesthetics work by interfering with the excitability of all neurons, not just the pain-sensing ones, thereby leading to the side effects of temporary paralysis for local anaesthetics and loss of consciousness in the case of general anaesthetics. While still in its infancy, the new combination is being seen by the researchers as somewhat of a breakthrough. "We're optimistic that this method will eventually be applied to humans and change our experience during procedures ranging from knee surgery to tooth extractions," Massachusetts general hospital Professor Clifford Woolf, a senior author on the study. The new drug combination builds on research done since the 1970s and effectively uses capsaicin in an innovative drug delivery role for QX-314. QX-314 does not have the ability to penetrate cell membranes, unlike other anaesthetics, and typically lingers outside neurons without having any effect. But if QX-314 can enter cells it has the same anaesthetic powers. This is where capsaicin comes in. The chilli ingredient acts on a certain membrane-spanning protein, TRPV1, which is only found on pain-sensing neurons. TRPV1 is a gated channel allowing molecules to enter and exit the cell but controls the flow of molecules by whether the "gate" has been opened or not. In the presence of capsaicin, or when the cells are exposed to heat, the gate will open. Once the gates are open, QX-314 is able to enter the pain-sensing cells and initiate its anaesthetic effect. Because QX-314 has not been able to enter the other neurons, they retain their full and normal function. In vitro studies found the combination of capsaicin and QX-314 selectively blocked the excitability of pain-sensing neurons, leaving the others unaffected. In rat models, the same was seen to be true. The researchers still have to develop the formulation before it could be applied to humans. They must figure out how to open the TRPV1 channels without producing even a transient burning pain before QX-314 enters and blocks the neurons and they must experiment with the formulation to prolong the effects of the drugs. "Eventually this method could completely transform surgical and post-surgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis," Woolf said. Capsaicin is currently used to relieve pain as a topical ointment and cream.