Safer Nerve Blocks--A Promising Combination Local Anesthetic

I have a great deal of experience in this area of medicine--providing spinal blocks, epidurals, regional nerve blocks etc. Most persons in the profession of anesthesia or pain treatment have wanted a local anesthetic with the properties claimed for this experimental combination drug:

“We’ve introduced a local anesthetic selectively into specific populations of neurons,” explains Harvard Medical School Professor Bruce Bean, an author on the paper, which appears in Nature on Oct. 4. “Now we can block the activity of pain-sensing neurons without disrupting other kinds of neurons that control movements or non-painful sensations.”

“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,” adds Professor Clifford Woolf of Massachusetts General Hospital, who is senior author on the study.

Despite enormous investments by industry, surgical pain management has changed little since the first successful demonstration of ether general anesthesia at MGH in 1846. General and local anesthetics 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.

“We’re offering a targeted approach to pain management that avoids these problems,” says Woolf.

...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 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.

...The team must overcome several hurdles before this method can 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 tinker with the formulation to prolong the effects of the drugs. Both Bean and Woolf are confident they’ll succeed.

“Eventually this method could completely transform surgical and post-surgical analgesia, allowing patients to remain fully alert without experiencing pain or paralysis,” says Woolf. “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.”

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I am looking forward to such an anesthetic becoming available.