Cluster Attack

Jurgens TP, Busch V, Opatz O, Schulte-Mattler WJ & May A. (2008) “Low-frequency short-time nociceptive stimulation of the greater occipital nerve does not modulate the trigeminal system” Cephalalgia 28:842-846 (Click author to see paper)

Dr. Sewell’s comment:

2007 was a big year for occipital nerve stimulation. Drs Burns and Goadsby in San Francisco published their long-term follow-up of occipital nerve stimulation in eight medically intractable patients; Dr. Magis and the Belgian team implanted occipital nerve stimulators in eight drug-resistant chronic cluster headache patients to good effect; and Dr. Schwedt at the Mayo xxx. So as we return to the May lab for our final look at the theory behind occipital nerve effects on cluster headache, we fast-forward another year to see that they, too, have decided to take a look at occipital nerve stimulation (which you would think would do the opposite from occipital nerve block, but strangely, does not):

AUTHORS’ ABSTRACT:    Occipital stimulation in a small group of refractory chronic migraine and cluster headache patients has been suggested as a novel therapeutic approach with promising results. In an earlier study we have shown that a drug-induced block of the greater occipital nerve (GON) inhibits the nociceptive blink reflex (nBR). Now, we sought to examine the effects of low-frequency (3 Hz) short-time nociceptive stimulation of the GON on the trigeminal system. We recorded the nBR responses before and after stimulation in 34 healthy subjects. Selectivity of GON stimulation was confirmed by eliciting somatosensory evoked potentials of the GON upon stimulation. In contrast to an anaesthetic block of the occipital nerve, no significant changes of the R2-latencies and R2-response areas of the nBR can be elicited following GON stimulation. Various modes of electrical stimulation exist with differences in frequency, stimulus intensity, duration of stimulation and pulse width. One explanation for a missing modulatory effect in our study is the relatively short duration of the stimulation.

Having shown a year earlier that occipital nerve block produces an abnormality in the reflex that causes people to blink in pain (the “nociceptive blink reflex”), thus demonstrating a link between the occipital nerve and the trigeminal nerve, which is what hurts in cluster attacks, Dr. Jürgens (who is on the same team as Dr Busch and Dr. May) decided to see if occipital nerve stimulation caused the same abnormality in the blink reflex. If it did, then we would be one step closer to understanding why occipital nerve stimulation was helpful for cluster headache as well.

So Dr. Jürgens took 34 healthy people—not headache sufferers—and inserted two electrodes in the back of their heads, midway between that bump you can feel in the middle of the back of the head (the occipital protuberance) and the bony bump behind you can feel behind your ear (the mastoid process). This corresponds to the location of the occipital nerve. He then stimulated their occipital nerves and measured R2, which as you will recall, is the part of the blink reflex that appears to mark the junction between the trigeminal and occipital nerves.

Much to everyone’s surprise, nothing happened! Dr. Jürgens cranked up the amperage to “maximum discomfort but not yet unbearable”, but the R2 did not so much as budge. He checked the occipital somatosensory evoked potential—check, the electrodes were in the right place. He checked sensory perception thresholds and pinprick sensation on the forehead—no change. Damn strange! Even stranger, several hours later, two of the subjects came down with stabbing one-sided headaches that lasted six hours—and remember these were healthy people who didn’t tend to get headaches. So something was going on—but what?

Science doesn’t always give you the answers you expect—that’s what distinguishes it from religion, and also what makes it fun. Clearly, whatever’s going on with occipital nerve stimulation is NOT what’s going on with occipital nerve block. Dr. Jürgens came up with a number of explanations for his experiment’s unexpected non-results.

The first is that he didn’t stimulate long enough. In rat models of inflammatory pain, fifteen minutes or an hour of stimulation causes long-lasting pain relief, but a minute does not. Dr. Jürgens stimulated his subjects from between 45 seconds to four minutes; perhaps not long enough. The first guy to promote electrical nerve stimulation, Dr. Melzack back in 1975, did it for twenty minutes, and most scientists since then have stuck to that. Most people (including the subjects in this study) aren’t (and weren’t) willing to put up with “maximum discomfort” for that long though.

Another possibility is that there’s something different about the brains of migraineurs or cluster headache patients that makes them respond to electrical nerve stimulation in a way that healthy normals do not. Well, could be!

And yet another possibility is that the frequency was just too low. Dr. Jürgens picked 3 Hz (three pulses a second) because rats have more analgesia at 3 Hz than they do at 15 Hz or 100 Hz, but the fact is that most human therapeutic studies use much higher frequencies (more than 100 Hz), so this study might have been looking for apple seeds in an orange.

But the most likely explanation, in my book, comes from the observation that although pain relief from occipital nerve stimulation tends to come pretty much straight away in migraineurs, in cluster headache patients stimulation generally has to be maintained for weeks to months before it starts to work. What’s going on? Neurons in the trigeminal pain system sprouting new branches, pruning others? Probably, and nothing that’d you’d pick up in an afternoon’s experiment.

Which leads us to the paper of three months ago that stimulated this brief detour into the history of occipital nerve stimulation: http://www.clusterattack.com/blog/wp-content/uploads/2009/09/burns-2009-treatment-of-intractable-chronic-cluster-headache-by-occipital-nerve-stimulation-in-14-patients.pdf. We don’t know why it works, but it works. And you can say that about most treatments for cluster headache!

This entry was posted on Wednesday, December 23rd, 2009 at 3:25 am and is filed under Theory, Treatment. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.