Histamine Inhibitory??? Back to the drawing board.

Here is a real shocker. Histamine, a pain player, can inhibit pain. Those of you who have completed the survey informed us aspirin and acetaminophen don’t help your central pain. Turns out you were ahead of your time.


Ask any physician about histamine, and you will get a popular, packaged lecture about its important role with proinflammatory cytokines in the immune process, which is partly responsible for the pain that comes with injury or infection. Even fake doctors and movie stars can lament histamine on TV ads. The lecture you get will be authoritative, organized, and spoken with learned assurance. Since doctors have histamine down cold, giving out antihistamines every day, the explanation will be correct about Histamine as it acts on the H1 and H2 receptors (Knocking out H2 receptors in the stomach has made several drug companies fabulous amounts of money). The only problem is the lecture will be dead wrong about Histamine 3 receptors. New research has rudely interrupted our comfortable positions of long held knowledge. H3 receptors inhibit pain.

What the pain chemicals????

It’s true, The unthinkable has happened. As it turns out, the evil little monster histamine that serves no good purpose we knew of, in the same philosophical category as why god invented mosquitoes, this little histamine molecule does something GOOD!!!.

We have emphasized elsewhere that the nature of the transmitter is not nearly so important as the nature of the receptor on which it acts. We never expected histamine to fall into this category and are just as dumbfounded as everyone else to learn that the Histamine 3 receptor is inhibitory.

Histamine reduces pain when it activates the H3 receptor. Once again, the survey comes to our rescue,however. Histamine 3 receptor stops pain from things like tail pinch in the rat, or in other words phasic pain, However, it has absolutely no inhibitory effect on thermal pain, and the kinds of pain associated with central pain. This is what the survey has told us for years. OTC pain meds against histamine aren’t helpful in CP, eg. aspirin and acetaminophen. Aspirin works on cyclooxygenase while acetaminophen works on prostaglandin synthase (downstream from histamine).

Despite this terribly iconoclastic revelation about H3, there are other studies that hint these two drugs do help pain if you really tank up on them, far exceeding the common dosages, at which level they even inhibit the proinflammatory effects of TNF alpha administered in the spihal fluid. (TNF alpha is a growth factor that is involved in repair of nerve injury and which is linked to nerve injury hypersensitization). Do NOT go out and alter your dose, since you can cause ulcers, bleeding, and interference with other meds. You must always consult your doctor. If you have been following, you see a contradiction. Aspirin and acetaminophen are not likely to help central pain, but they may help ordinary pain. Somewhere, somehow, drugs to stimulate H3 activity may HELP pain, but not central pain. This has not been worked out, so wait for proper study.

Thus, we see that the pain system is anything but simple. Cannon and Hough, the authors of the article are even suggesting that drugs similar to immepip, an H3 agonist (acts like H3) would be useful to treat pain, but only certain types of pain. The world is an amazing place. We wish we could claim we saw this coming, but we simply did not. We continue to find out more about pain, about what works and about what does not work. And just for the record, it doesn’t pay to get cocky about what we think we know about pain, or what ought to relieve it. The nervous system is what it is, with utter disregard for anyone’s theories, no matter how much sense theories make or how many people subscribe to them So don’t feel bad if your doctor isn’t bullseyeing your pain. No one is really on firm ground for nerve injury pain right now. We include this article to emphasize that the authors are NOT claiming benefit from H3 stimulators for THERMAL type pain.

See J Pain. March 2005 Inhibition of chemical and low-intensity mechanical nociception by activation of histamine H3 receptors. by Cannon KE, Hough LB.