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Letters to the Editor

PPM Editorial Board answers letters from readers. Can nitrous oxide potentiate pain management or eliminate pain altogether?

Question: Pain Relief After Dental Procedure

I had an unusual occurrence. A patient of mine with back pain (thought to be due to mercury poisoning) was receiving methadone for pain management and stimulants to treat attention deficit/hyperactivity disorder (ADHD). 

The gentleman went to his dentist for a dental extraction and received meperidine (Demerol) and nitrous oxide as part of the sedation during the extraction experience. When I saw him again, he reported that after the dental procedure he had complete relief of his back pain and believed that the nitrous oxide and/or Demerol played a role in his relief.  His relief lasted for 3 months, at which time he repeated the sedation, and again reported the pain was gone and was able to stop all other opioids. 

What, if any, is your experience with nitrous oxide as a facilitator for chronic pain relief?  There may be some data suggesting that it may affect the N-methyl-D-aspartate (NMDA) receptors and, in theory, could decrease pain wind up.  Any thoughts?

Scott Hompland, DO

Dear Dr. Hompland,

As you acknowledged, there is much research in the area of nitrous oxide and various pain pathways.1-5 Nitric oxide affects pain signaling associated with NMDA and tyrosine kinase proteins, but counterintuitive to your experience, it is an activator. Therefore, nitrous oxide would more likely increase pain by this mechanism. Nevertheless, some literature suggests that nitrous oxide can be helpful for inflammatory pain locally, and there are evidence utilizing nitrous oxide inhibitors to reverse hyperalgesia and opioid tolerance.

Jeff Fudin, BS, PharmD

Your experience isn’t really unexpected or, in some ways, not unusual. What you really touch upon is the theory of “re-set”. This theory, principally expounded by practitioners of electromagnetic medicine, is that some challenge to the neurophysiologic systems may cause re-programming. Nitrous oxide and meperidine are both potent agents that can have an immediate effect on receptors and neurotransmission. For example, a local anesthetic, such as lidocaine, procaine, or bupivacaine, when given as a local ”trigger point” injection or topical application may “re-set” electrical transmission and provide temporary or even permanent “cure of pain” because the nerve membrane electrical potentials are altered. 

I assume that you have witnessed a re-set of receptors and electrical transmission due to nitrous oxide and/or meperidine. Perhaps it is worth noting that meperidine may produce pain relief in an occasional patient when no other agent will do so.  All in all, I very much appreciate your observation since it makes us all “think outside the box.”  Do you know of anyone who has given nitrous oxide at low doses in an ambulatory clinic?  Perhaps someone should try it.  Thanks for sharing your stimulating observations.

Forest Tennant, MD, DrPH

I know of nitrous oxide being used to help in labor for pain, as well as an adjunct in interventional procedures (ie, cryoablation), but I’ve never heard of it being used, and more importantly, having effects lasting 3 months, for chronic lower back pain.

Gary Jay, MD

Nitrous oxide use goes back to the 1840s, when a dentist named Horace Wells (associate of William Morton of ether fame) began using it for pain relief and anesthesia during dental procedures. Demerol has been taken off formulary in many hospitals because of the rare seizure side effects. At Scripps, for example, meperidine can only be used for the treatment of shivering. The combination of nitrous oxide and meperidine could have a synergistic effect—Demerol also has a local anesthetic effect and this could also play a role in this case.

Joseph Shurman, MD

Last updated on: May 19, 2015
First published on: December 1, 2013