A new combination of compounds blocks pain without affecting other sensations or motor function.
Anesthetics used for local and regional anesthesia block pain signals from pain-sensing (nociceptive) neurons. However, they also affect the function of other sensory neurons and (in the case of regional anesthesia) of autonomic neurons and motor neurons as well. They do so because current anesthetics easily diffuse through the lipid membranes of all types of neurons.
Recently, nociceptive neurons have been found to have unique ion channels, called TRPV1 channels, that open in response to a few stimuli, including the irritating molecule capsaicin (the substance that makes chili peppers "hot"). A team from Harvard Medical School combined a lidocaine derivative called QX-314, which cannot pass through lipid membranes on its own, with capsaicin. TRPV1 ion channels opened by capsaicin allowed QX-314 to enter nociceptive neurons, blocking their function. When the combination was injected into the feet or near the sciatic nerves of live rats, it inhibited the response to pain for several hours but did not inhibit motor neurons.
Comment: This discovery could lead to selective inhibition of pain by local and regional anesthesia, without the unwanted side effects of inhibiting other sensations or autonomic and motor function. Recurrent application also might help treat various chronic pain syndromes mediated by chronic low-level stimulation of nociceptive neurons. This novel and simple technique now needs to be tested in humans.
Published in Journal Watch General Medicine October 11, 2007
Binshtok AM et al. Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 2007 Oct 4; 449:607.