(Please welcome Tim Vaughan to Health Rising’s team of bloggers as he digs deeper into issues raised in earlier blogs and outlines an intriguing theory about the nature of pain in fibromyalgia, chronic fatigue syndrome and other disorders.)
Touch the tip of your forefinger to the tip of your thumb so that you are almost making that sign for, “all’s well”. Now imagine that when the two tips touch, it hurts. A lot! Now, imagine that any light touch of your fingers produces the same results: typing, petting an animal, tapping the screen of your smart phone/tablet… the list can go on and on.
This is allodynia, a dysfunction of the sensation of touch which has long been associated with Chronic Regional Pain Syndrome, but is nowadays recognized in the medical community as a prominent feature of fibromyalgia, migraine and even chronic fatigue syndrome (ME/CFS). Almost 80% of FM patients tested positive for allodynia in one study.
A Wide Reach
Allodynia is not confined to the fingertips, it can occur anywhere on the body. It can make wearing clothing, or hugging a nightmare. Still trying to conceptualize the hypersensitivity associated with allodynia? Think of the last time you bruised your toes or fingers. They became inflamed and swelled. When you lightly touched them they hurt like hell. When your clothing brushed against that spot, it was almost unbearable! That’s allodynia.
If you have ever read about fibromyalgia, one of the primary concepts is the existence of “tender points”. My guess is that these tender points are just spots displaying the hypersensitivity of allodynia. Allodynia is a relatively new term in the medical field but several different types have been identified:
1. Mechanical/Tactile allodynia
- Static mechanical allodynia – pain in response to light touch/pressure
- Dynamic mechanical allodynia – pain in response to brushing
2. Thermal allodynia – pain from mild hot or cold temperature applied to the skin.
Mechanical allodynia is possibly the most persistent disabling symptom I experience. Often considered a nervous system phenomenom and labeled as nerve pain, some evidence suggests, it may be more due to muscular ischemia-reperfusion and autonomic system dysfunction than actual nerve injury.
I recently learned about ischemia-reperfusion injury when, after a stroke, my father was diagnosed as having Transient Ischemic Attacks (mini strokes). It was difficult for me to get my mind around this concept of ischemia-reperfusion injury until I read this explanation from Cort’s recent blog on exercise, muscle pain, and ischemia:
‘Ischemia’ occurs when blood flows to a tissue are low enough to reduce the level of oxygen and glucose needed for cellular energy production. The problem is actually not the ischemia per se but what comes after it; in what must be one of nature’s weirdest tricks, re-infusing tissues that have been deprived of oxygen with oxygen again can cause a serious problem called ‘reperfusion injury’.
It turns out that the absence of oxygen – which means the switching on of anaerobic metabolism and the production of toxic-by products – creates an environment posed for inflammation. Oxygen is a mild free radical and throwing it back into an oxygen deprived environment can result in an explosion of stronger free radicals such a nitric oxide, superoxide and finally peroxynitrite (e.g. Dr. Pall’s). Bizarrely, as that’s going on white blood cells may also bind to the endothelial cells lining the small blood capillaries, once again blocking the flow of the blood….Depriving your cells of oxygen is not something you want to do, even temporarily.
The Ischemia-Reperfusion Allodynia Connection
What does muscle-ischemia have to do with pain so severe that the lightest touch can cause extreme pain? Perhaps a lot…That explanation above sets the stage for a look at a 2008 paper on mechanical allodynia, “Cutaneous Tactile Allodynia Associated with Microvascular Dysfunction in Muscle”.
Canadian researchers at McGill University investigated whether an ischemia-reperfusion (IR) injury produced allodynia in rats, and whether that allodynia was associated with micro-vascular dysfunction in muscles. First they induced allodynia symptoms in the hind foot of the rats, and then showed that micro-vascular dysfunction leads to persistent muscle ischemia and allodynia. Their statements ring similar to some in Cort’s “ischemia” blog:
…it is likely that allodynia depends on ischemia-reperfusion injury and resultant micro-vascular dysfunction, which may include arterial vasospasms and capillary slow flow/no-reflow. Arterial vasospasms occur due to a reduction in nitric oxide-induced vasodilatation and hyper-responsiveness of arterial smooth muscle cells to norepinephrine.
Capillary slow flow/no-reflow is the phenomenon that Cort mentioned in his “ischemia” blog where the capillary walls become clogged with platelets and white blood cells, thus blocking oxygen from reaching the muscle. Now the muscle has to deal with lack of oxygen and the inflammation cascade from reperfusion. As Cort mentioned, this sets up a great environment for the generation of pain.
Next, the McGill group measured lactate levels associated with the muscle ischemia and found evidence that increased lactate was associated with ischemia induced muscular allodynia in the rat’s hind paws. Cutaneous nerve abnormalities were not associated with the muscle ischemia, meaning this was not a dysfunction of the nerves per se, instead, it appeared to result from ischemia-reperfusion, vasospasms and the resulting lactate buildup.
“A Strong Reluctance to Exercise”
They also found that these rats exhibited, “a strong reluctance to exercise” presumably because exercise made their allodynia and muscle pain worse. They suggested that muscle ischemia results in the generation of a higher basal (at rest) level of lactate in these rats contributing to pain and allodynia at rest.
After forcing these poor rats to exercise they found high levels of lactate and exercise-induced persistent pain and allodynia occurring days later. Maybe I should repeat that for emphasis…the rats experienced increased pain days after the exercise. That sure sounds a lot like a form of postexertional malaise to me.
Anybody else perplexed by the elevated pain and misery you experience the next day and the day after performing some sort of muscular exertion? Could these ‘allodynic’ rats experiencing the same thing people with ME/CFS are?
The Muscle -Central Sensitization Link
Then the McGill group turned to looking at the “central sensitization” of allodynia in these rats. They noted that other researchers could induce allodynia for several hours by injecting nerve pain-producing substances (capsaicin or carrageenan) into the skin
Injecting these substances into rat muscles produced a very different story; this time the central sensitization and allodynia lasted much longer, up two weeks. Something about muscle induced as opposed to skin induced allodynia causes a much longer period of ‘system reset’.
The McGill researchers believe the micro-vascular changes associated with ischemia constantly prime the phenomenon of “central sensitization of pain”, resulting in prolonged long-term central nervous system sensitization that shows up in allodynia, muscle dysfunction and way too much pain.
Anybody out there have tight, ropey, hard-feeling muscles that become fatigued and painful (with associated allodynia) way, way too easily?
These authors take on the central sensitization (and the resulting pain) in fibromyalgia is different than most researchers who concentrate on the brain and changes in the brain from sensitization. The brain researchers have relied on brain imaging studies and measuring catecholamine (serotonin, dopamine, norepinephrine, etc.) changes in the brain’s chemistry. The McGill University’s researchers maintain changes in the micro-vascular structures of the muscles cause a cascade of events that constantly sensitize the muscles and the skin to pain, resulting in ever continuing central sensitization. As this diagram of theirs shows:
Figure 1. Laferriere, et al., “Schematic diagram indicating proposed mechanisms for initiation/maintenance of cutaneous tactile allodynia after IR injury”, figure 7, October 2008, Molecular Pain,4:49.
Considering the information in this McGill University study, an alternative clinical approach to try to alleviate allodynia might to focus on the autonomic system rather than relying on the commonly used approach of brain drugs (Cymbalta, Savella, Gabapentin, etc.).
What is causing this micro-vascular ischemia and reperfusion? One possibility is an autonomic system is in disarray resulting in too much constriction of the micro-vascular system resulting in ischemia and the resultant reperfusion damage. Do you have postural orthostatic tachycardia syndrome (POTS)? You have a dysfunctional autonomic system. You have allodynia? You might have a dysfunctional autonomic system as well. Do you have have muscle pain? You might have a dysfunctional autonomic system as well.
- Find ways to increase blood volume and perhaps avoid some ischemia in Enhancing Blood Volume in Chronic Fatigue Syndrome and Fibromyalgia
After years of work it’s time to attempt what we’ve never been able to do before – get Congress to force the NIH to double its funding for ME/CFS. Support the historic bill to increase research funding, add new ME/CFS research centers, require the development of a strategic plan, etc.. It will take less than 5 minutes.