Washington, DC, USA. General anesthesia puts patients into unconscious sleep so they do not feel surgical pain, but researchers say it can increase their discomfort once they wake up.

 

The findings provide scientific confirmation for an increasing number of anecdotal observations in clinics.

 

In the Proceedings of the National Academy of Sciences (PNAS), scientists report that "noxious" anesthesia drugs — which includes most of these general anesthetics - activate and then sensitize specific receptors on neurons in the peripheral nervous system. These are the sensory nerves in the inflammation and pain pathway that are not affected by general anesthesia drugs that target the central nervous system – the brain and the spinal cord.

 

---

General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. José A. Matta, Paul M. Cornett, Rosa L. Miyares, Ken Abe, Niaz Sahibzada, and Gerard P. Ahern. PNAS 2008 105(25) 8784-8789. 10.1073 / pnas.0711038105  [ Supporting Info PDF ]

---

 

Research from the Georgetown University Medical Center (GUMC) may lead to wider use of the few anesthetics that don't have this side effect, or to new developments.

 

"The choice of anesthetic appears to be an important determinant of post-operative pain," according to Gerard Ahern, Ph.D., an assistant professor in the GUMC Department of Pharmacology. "We hope these findings are ultimately helpful in providing more comfort to patients."

 

Ahern says that general anesthetics have long been known to cause irritation at the infusion site or in the airways when inhaled.

 

And investigators have also known that while they suppress the central nervous system, they can activate so called "pain-sensing" or nociceptive nerve cells on the peripheral nervous system — in fact, anesthesiologists often first use a drug to suppress inflammation and pain before delivering the anesthesia to put the patient to sleep.

 

But what has not been understood is the specific mechanism by which anesthetics affect sensory neurons, or that they can continue to cause pain and inflammation even as they are being used during surgery, says Ahern, the study's lead investigator.

 

The researchers tested the hypothesis that two specific receptor on the nerves cells (TRPV1 and TRPA1) which are often expressed together and which also react to other irritants, such as garlic and wasabi, were the ones activated by the noxious drugs.

 

"Plants produce chemicals such as capsaicin, mustard and garlic that were meant to stop animals from eating them. When they are eaten, the two main receptors that react to them are TRPV1 and TRPA1," he says. In fact, TRPA1 is more commonly known as the mustard-oil receptor, and is a principal receptor in the pain pathway, Ahern says.

 

Experiments showed that general anesthetics appear to regulate TRPA1 in a direct fashion, and are thus responsible for the acute noxious effects of the drugs. Perhaps the strongest evidence is that mice bred without TRPA1 genes demonstrate no pain when the drugs are administered and used, Ahern says. "Most general anesthetics activate the mustard oil receptor, and animals that don't have the receptor don't have irritation," he says.

 

The research team also found that nerve-mediated inflammation was greater when pungent (chemical irritants) versus non-pungent inhaled general anesthetics were used.

 

What both findings suggest is that sensory nerve stimulation throughout the body just before and during surgery adds to the pain that is felt after the patient is awake, Ahern says. "This is a provocative finding in terms of the clinical setting, because it was not really recognized that use of these drugs results in release of lots of chemicals that recruit immune cells to the nerves, which causes more pain or inflammation."

 

Some general anesthetics do not activate the mustard-oil receptor, but they may not be as effective in other ways, Ahern says. "This tells us that there is room for improvement in these drugs."

 

The study was funded by the National Institutes of Health (NIH) and the National Multiple Sclerosis Society. All co-authors are from Georgetown University.

 

General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. José A. Matta, Paul M. Cornett, Rosa L. Miyares, Ken Abe, Niaz Sahibzada, and Gerard P. Ahern. PNAS 2008 105(25) 8784-8789. 10.1073 / pnas.0711038105  [ Supporting Info PDF ]

Abstract

General anesthetics (GAs) have transformed surgery through their actions to depress the central nervous system and blunt the perception of surgical insults. Counterintuitively, many of these agents activate peripheral nociceptive neurons. However, the underlying mechanisms and significance of these effects have not been explored. Here, we show that clinical concentrations of noxious i.v. and inhalation GAs excite sensory neurons by selectively activating TRPA1, a key ion channel in the pain pathway. Further, these GAs induce pain-related responses in mice that are abolished in TRPA1-null animals. Significantly, TRPA1-dependent neurogenic inflammation is greater in mice anesthetized with pungent compared with nonpungent anesthetics. Thus, our results show that TRPA1 is essential for sensing noxious GAs. The pronociceptive effects of GAs combined with surgical tissue damage could lead to a paradoxical increase in postoperative pain and inflammation.

 

 

Name

Email

Title

Comment

smaller | bigger

I have read and agree to the Terms of Use.

Write the displayed characters

Add Comment