Stimulated by Giannini et al 2021, and Szikszay et al 2020.
Botox – botulinum toxin type Akey to acronyms
CG150 – NICE Clinical Guideline 150 (Headaches in over 12s)
GERAC – GERman ACupuncture trial
RR50 – responder rate defined by a 50% reduction in days with headache
OA – Offset Analgesia (surely they could have used a different acronym!)
CPM – Conditioned Pain Modulation
It was only a month ago that I addressed a rather similar topic, but I could not help revisiting it for this rather unique trial. Last time we were concerned with chronic migraine, and so Botox got a look in, but here we are dealing with episodic migraine, and it doesn’t. Instead we have a pragmatic head to head trial pitting 12 sessions of acupuncture against the best medical therapy selected on an individual basis for each patient. As far as I know, this is the first trial to do this, although the large GERAC migraine trial did use a set of three possible drugs in their standard care group.
This trial included a large variety of different drugs, and combinations of drugs with vitamins and other supplements, all apparently following international guidelines. This list is certainly more extensive than what is listed in CG150, but the main drugs are still all represented.
The treatment phase lasted 4 months and then both groups stopped the prophylactic treatments. The main outcomes were measured at this time point but follow up continued for a further 6 months.
Dropouts and withdrawals were a significant factor, especially during follow up. Of the 135 patients randomised, only 103 completed the course of treatment. During follow up most patients withdrew due to the need for on-going treatment. Only 40 made it to the end of follow up, and 30 were from the acupuncture group and 10 from the drug group.
There were no differences in the main outcomes at any time point, although compliance was better for acupuncture and the rate of adverse events was lower.
The overall success was somewhat less than we have seen previously, with an RR50 of 34% overall. The RR50 figures for GERAC migraine were 47%, 39% and 40% respectively for acupuncture, sham and drug prophylaxis. The figures for the ART migraine trial were even better, coming in at 51%, 53% and 15% respectively for acupuncture, sham and waiting list.
So, this is the first trial where there seems to have been a genuine attempt to choose the best pharmacological treatment for individual patients, but it is somewhat unusual in forcing this treatment to stop at the same time as the acupuncture.
The second paper I am highlighting is from last year, and it studies a form of pain modulation in patients with migraine and compares this with age and sex-matched headache-free subjects. The modulation phenomenon is called offset analgesia (OA), and it is defined as a disproportionately large decrease in pain perception in response to a small decrease in painful stimulation.
They recruited 26 subjects to each group and used a thermal stimulus at two different sites for the experiment, one within the distribution of the trigeminal nerve (forehead) and the other outside it (forearm). In the patients with episodic migraine they used the forehead on the side of most frequent headache and the forearm that was contralateral. In the healthy subjects the selection was a random side.
The thermal stimulus was applied over 30 seconds each time and was either constant or stepped up by 1 degree for 5 seconds after the first 5 seconds of constant thermal stimulus. The baseline level of thermal stimulus was individualised and aimed for a subjective level of pain that measured 60 out of 100 – so called Pain60.
A computerised VAS on a 0 to 10 scale was used to measure pain perception throughout the experiments and the subjects were asked to pay attention to even small differences in pain. It is not stated how often they were expected to adjust the rating or how often that rating was sampled, but the graphical results in the paper have data points every second.
The main outcome was the difference in rating between a constant thermal stimulus and the stimulus pattern with an early step for a 10 second period that started at about 17 seconds, well after the step if there was one. The results show a clear difference that demonstrates the OA phenomenon, but the point was not to demonstrate the phenomenon, but to compare the size of the effect in different groups and in different sites.
The main finding was that OA was significantly reduced on the forehead (trigeminal) in patients with migraine, but not on the forearm (extratrigeminal). This implies some abnormality of sensory processing that affects the head but not segments farther away.
Wouldn’t it be interesting to see whether or not a course of acupuncture could improve or normalise this measure in a similar way as CPM has been shown to change in patients with knee osteoarthritis?
That last comment refers to a paper highlighted here previously: Strong EA and CPM in OAK.
1 Giannini G, Favoni V, Merli E, et al. A Randomized Clinical Trial on Acupuncture Versus Best Medical Therapy in Episodic Migraine Prophylaxis: The ACUMIGRAN Study. Front Neurol 2021;11:570335. doi:10.3389/fneur.2020.570335
2 Szikszay TM, Adamczyk WM, Carvalho GF, et al. Offset analgesia: somatotopic endogenous pain modulation in migraine. Pain 2020;161:557–64. doi:10.1097/j.pain.0000000000001739
3 Diener H-C, Kronfeld K, Boewing G, et al. Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol 2006;5:310–6. doi:10.1016/S1474-4422(06)70382-9
4 Recommendations | Headaches in over 12s: diagnosis and management | Guidance | NICE. https://www.nice.org.uk/guidance/cg150/chapter/Recommendations (accessed 9 Jan 2021).
5 Cummings M. Modellvorhaben Akupunktur–a summary of the ART, ARC and GERAC trials. Acupunct Med 2009;27:26–30. doi:10.1136/aim.2008.000281
6 Linde K, Streng A, Jürgens S, et al. Acupuncture for patients with migraine: a randomized controlled trial. JAMA 2005;293:2118–25. doi:10.1001/jama.293.17.2118