Researchers from Massachusetts General Hospital and Harvard Medical School have found a way to target only pain-sensing neurons when injecting a local anesthetic. The technique blocks pain without affecting motor function or sensitivity to non-pain stimulus.
While current local and general anesthetics work well for controlling pain, since they work by interfering with the excitability of all neurons and not just pain-sensing neurons, they produce dramatic side effects—loss of consciousness for general anesthetics, and loss of motor function for local anesthetics.
The experimental results were achieved in rats by combining a normally inactive lidocaine derivative (QX-314) with capasicin, the "hot" ingredient in chili peppers.
According to the researchers, the results of their new technique were achieved by taking advantage of 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. In this case, that gate is opened when the cells are exposed to the heat of the capsaicin. Non-pain sensing neurons are unaffected because they do not possess TRPV1.
The lidocaine derivative QX-314 is not used clinically because it can’t penetrate cell membranes to block the excitability of the cell, so it typically remains outside the neurons. In this case, that property is a benefit to the new pain management technique. When pain-sensing neurons are exposed to capsaicin, however, 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 so they retain their ability to send and receive signals.
"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," says the study’s senior author, Professor Clifford Woolf of Massachusetts General Hospital. "Eventually this method could completely transform surgical and post-surgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis."
The study appears in the October 4, 2007 issue of Nature.
Source: Harvard Medical School