Saturday, December 19, 2009

stealth sensation and idle speculation

In skimming the medical news in preparation to comment on the now slightly less insane coverage of both influenza and the new USPSTF mammography guidelines, I was distracted by this headline from Science Daily: "Hidden Sensory System Discovered in the Skin." Hidden sensory systems, eh? Casting a dubious eye, I proceeded to read onward to see what anatomists might have been missing over the last several hundred years:
The human sensory experience is far more complex and nuanced than previously thought, according to a groundbreaking new study published in the December 15 issue of the journal Pain. In the article, researchers at Albany Medical College, the University of Liverpool and Cambridge University report that the human body has an entirely unique and separate sensory system aside from the nerves that give most of us the ability to touch and feel. Surprisingly, this sensory network is located throughout our blood vessels and sweat glands, and is for most people, largely imperceptible. (full story at ScienceDaily.com)

So far, so good, if a bit sensationally described. The existence of nerves that wire our glands to secrete the substances they produce, and blood vessels expand or contract in response to certain signals, is certainly not news. The interesting thing here is the idea that they may be somehow involved in detecting sensation from the skin, which is something that's never been considered before - after all, we already have an extensive set of nerves in place that do just that.

This particular research came about when two unrelated patients were evaluated by the paper's authors due to their similar, and previously unsubscribed, constellation of symptoms. Both had a congenital inability to feel pain, as manifested by the patients being unaware of significant injuries, such as broken bones, exposure to severe cold, and burns. In addition to other symptoms, both patients did have some degree of sensation to non-painful stimuli, which allowed them to accomplish their daily tasks and employment without any difficulties. The subjects underwent a detailed clinical neurological exam, as well as nerve biopsies and DNA analysis. The results show that there was an almost total absence of normal sensory nerves to the skin, but with no genetic mutations present that have been associated with other "congenital absence of pain" syndromes. The journal authors concluded:
...Our findings suggest three hypotheses: (1) that development or maintenance of sensory innervation to cutaneous vasculature and sweat glands may be under separate genetic control from that of all other cutaneous sensory innervation, (2) the latter innervation is preferentially vulnerable to some environmental factor, and (3) vascular and sweat gland afferents may contribute to conscious cutaneous perception. (abstract from Pain, 2009; 147 (1-3): 287; full article requires subscription)

Translation: (1) the genes that control different nerve systems are more complex and separate than previously thought, (2) the nerves that directly wire for sensation in the skin may be affected specifically by things in the environment that might not effect other nerve systems, and (3) the nerves that control blood vessel dilation and gland function may have a role in skin sensation as well. These are very interesting, as well as appropriately conservative, conclusions - based on two patients with extremely rare conditions, we have some new ideas about how the nervous system works. This will likely spur on more research to investigate how these different nerves intersect in terms of sensory input, and the potential genes involved.

Of course, the very preliminary nature of these observations doesn't prevent the authors from speculating to the media on what these findings might mean for specific diseases. From the Science Daily report:
"Problems with these nerve endings may contribute to mysterious pain conditions such as migraine headaches and fibromyalgia, the sources of which are still unknown, making them very difficult to treat." (full story at ScienceDaily.com)

The implications of this discovery for migraine headaches in particular is, admittedly, tantalizing. What causes the pain in migraines is not fully understood, and several theories involve the abnormal responses of blood vessels in the brain and surrounding tissues. Certainly, the idea that nerves connected to said blood vessels could themselves be generating pain signals might have significant importance for managing and treating such headaches.

All that said, any speculation at this point as to how this discovery may relate to specific diseases is just that - idle speculation. Much like the recent poorly reported and overblown "association" of XMRV with chronic fatigue syndrome, it is inappropriate to draw any clinical conclusions about poorly understood syndromes like fibromyalgia based on the actual content of this study. What is important is that through the description of these two rare patients, we have made a fascinating discovery at a very basic level about how our nervous system may work normally, or at least attempt to compensate when a genetic change has happened. How this plays out in the future in terms of pain disorders remains to be seen.

[Journal reference: Bowsher et al. Absence of pain with hyperhidrosis: A new syndrome where vascular afferents may mediate cutaneous sensation. Pain, 2009; 147 (1-3): 287 DOI: 10.1016/j.pain.2009.09.007]

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