Source: The Times
Date: 4 October 2007

Chemical that gives chilli its bite is hot stuff at killing pain without numbness

Mark Henderson, Science Editor

An anaesthetic that can block pain without impairing movement, touch or mental awareness has been developed using the chemical that gives chilli peppers their kick.

The drug cocktail, based on capsaicin, promises to transform pain management by relieving the pain itself without disrupting other biological functions. It is likely to prove useful as an alternative to epidurals during childbirth, as it would not cause numbness or paralysis, allowing mothers to remain responsive to their bodies and more aware of the experience.

Other applications could include postoperative pain relief - particularly after joint surgery, when sensation can help rehabilitation - as well as in dentistry and in fighting the pain caused by chronic and terminal illness.

Unlike strong painkillers such as morphine, which are used in the later stages of cancer, it would not affect patients’ mental function. It could also be useful in sports medicine, allowing injured players to take part in important matches.

At present, most anaesthetics, including local anaesthetics such as lidocaine, work by shutting down activity in all types of neurons, causing numbness and paralysis. This is not normally a problem during general anaesthesia for major surgery, in which muscle relaxants are often given to prevent sudden involuntary movements. But it can be problematic when patients remain conscious or require relief from chronic pain. Numbness can be uncomfortable in itself, and the loss of touch, movement, co-ordination or mental alertness can be distressing or medically damaging.

The new anaesthetic, developed by scientists at Harvard Medical School in Boston, Massachusetts, uses a combination of two chemicals to target only pain-sensing neurons, or nocireceptors, while leaving other types, such as motor neurons, untouched.

The first element of the cocktail is QX-314, a derivative of lidocaine, which blocks electrical activity in neurons. On its own, however, it cannot get through cell membranes to cause this anaesthetic effect.

The second element, capsaicin, targets pain-sensing neurons, opening pores known as TRPV1 channels that are found in these nerve cells but not in other kinds. This means that QX-314 enters only nocireceptors, blocking pain without affecting movement or touch.

In a study published in the journal Nature, a team led by Professor Clifford Woolf and Professor Bruce Bean has shown that the combination therapy works well in rats. When injected near the sciatic nerves, which run down the hind limbs, the anaesthetic eliminated pain in their paws.

Five out of the six animals injected continued to move and behave normally, indicating that there had been no impairment of other neurological functions.

Professor Woolf said: “Surgical pain is the obvious first application for this treatment. 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.” Professor Bean added: “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.”

Story Landis, director of the US National Institute of Neurological Disorders and Stroke, which funded the study, said: “The holy grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, co-ordination, or other vital functions of the nervous system.

“This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major future breakthroughs for the millions of persons who suffer with disabling pain.”

Professor Woolf said: “Eventually this method could completely transform surgical and postsurgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis. In fact, the possibilities seem endless. I could even imagine using this method to treat itch, as itch-sensitive neurons fall into the same group as pain-sensing ones.”