Fibromyalgia and Excessive Peptidergic Sensory Innervation of Cutaneous Arteriole-Venule Shunts (AVS) in the Palmar Glabrous Skin

This morning MDLinx® Rheumatology directed my attention to the following study. P.J. Albrecht and colleagues published in May: “Excessive Peptidergic Sensory Innervation of Cutaneous Arteriole-Venule Shunts (AVS) in the Palmar Glabrous Skin of Fibromyalgia Patients: Implications for Widespread Deep Tissue Pain and Fatigue.” Link: http://www.ncbi.nlm.nih.gov/pubmed/23691965.

As fibromyalgia isn’t primarily a peripheral disease, it might not be a good idea to search there for clues. As peripheral pathologies are to expected in chronic pain conditions, one might not be too astonished to find such pathologies in fibromyalgia patients. The authors “hypothesized that this vascular location may be a potential site of pathology and/or serotonergic and norepinephrine reuptake inhibitors (SNRI) drug action.” But their study didn’t test this hypothesis.

“Twenty-four female FM patients and nine female healthy control subjects were enrolled for study, with 14 additional female control subjects included from previous studies.” N=24 and a “control” group with subjects from pervious studies is quite a toad to swallow, when it comes to “Implications for Widespread Deep Tissue Pain and Fatigue”.

“Importantly, the sensory fibers express α2C receptors, indicating that the sympathetic innervation exerts an inhibitory modulation of sensory activity.” I would expect this, too, as central inhibitory modulation isn’t working correctly any more in fibromyalgia patients, this is a way of adapting to the new condition.

The authors conclude: “… SNRI compounds may provide partial therapeutic benefit by enhancing the impact of sympathetically mediated inhibitory modulation of the excess sensory innervation.” But this isn’t a conclusion; it’s a repetition of the hypothesis!

I don’t want to question the results of this study, but the implications are farfetched. In this way the study may do harm. You can already see the resonance of this study on the net: “Once again, evidence that FMS includes a peripheral neuropathy”. The study nurtured the hope that with treating a peripheral neuropathy you can treat fibromyalgia. SNRI compounds are already used to treat fibromyalgia, but the effect size is very low.

To sum it up, the study annoyed me.

Addendum 08.07.2013:
Paul Sufka, rheumatologist and twitter friend supplied the following link: http://www.intidyn.com/Newsroom/article-0008.html.
Frank L. Rice, PhD, of Integrated Tissue Dynamics (INTIDYN) published an article on the company’s hompage concerning the cited study above: “Women with Fibromyalagia Have A Real Pathology Among Nerve Endings to Blood Vessels”.
The article dwells a lot on textbook knowledge instead of commenting on the findings. Here’s what I’ve found in his article: “…discovered that the skin in fibromyalgia patients has a major pathology involving nerve endings to a key type of blood vessel called arteriole-venule shunts.” The problem lies in the selection of patients and the small number (N=24). Who knows if this is only found in fibromyalgia patients and not also in patients suffering from hypertension, other forms of chronic pain, and so on? “… “and the discovered pathology involving the nerve endings to the shunts provides a logical explanation for the widespread deep pain and fatigue symptomatic of fibromyalgia.” It isn’t a logical explanation, it’s one hypothesis of more possible ones – and an unproven one.
“These molecular characteristics explain why some drugs such as Cymbalta and Savella provide some relief to some fibromyalgia patients.” Well, that’s the reason behind, to give a somatic construct to convince physicians to prescribe drugs, that have an effect, but the effect size is so small that I don’t recommend the use of the above mentioned drugs. Have a look at the study by F. Wolfe and colleagues: Longitudinal patterns of analgesic and central acting drug use and associated effectiveness in fibromyalgia. Link: http://www.ncbi.nlm.nih.gov/pubmed/23169685.