A Closer Look At The Relationship Between Sleep Disturbances And Chronic Pain

Stephen Barrett DPM FACFAS

It was unusual for the Midwestern summer to have an afternoon with such cool breezes as the winds rippled the wheat fields of the surrounding farms. I was stretched out on the bench seat of my uncle’s red 1964 Ford Fairlane. I had just finished one of those midday naps, which probably indicate some disturbance in my “sleep architecture” (that’s what the sleep experts call it).

While still in that not completely coherent, alert state, I was mentally wrestling with one of the true conundrums of medicine while drifting between that state of full wakefulness and that of level one sleep. Does chronic pain (and acute pain for that matter) interrupt normal sleep, or does a sleep disturbance increase one’s pain or propensity for pain? Does lack of sleep lower the pain tolerance of patients, which leads to chronic pain for some insomniacs? Should you talk with your patients about how they sleep?

Stretching out comfortably in my uncle Bob’s old flivver (this could never happen in our modern cars with consoles and bucket seats and yes — my God — seatbelts), I was staring down at my cowboy boot-shod feet, transfixed on the incongruity of color within my new “Lucky Brand” jeans. (No, I have no financial interest in the company and in fact probably paid more because there was not a perfect uniform color in them to begin with.) I realized that maybe there was something about gene incongruity (Get the play on words?) and gene expression, which made us all different and susceptible or not to insomnia and pain, and the delicate dance between them.

Now what we are talking about here is interesting stuff. This is partly because we know virtually jack about it and partly because in the next 10 years, we are going to be drawing blood or collecting some other bodily fluid, which will allow us to know who is going to sleep well after our surgery and who will not.

Why is this important for a foot and ankle surgeon, you may ask? Good question. We know for a fact that there is a definite relationship between sleep and its importance in maintaining inhibitory suppression of afferent nociception and insomnia, and interrupted sleep. Folks with chronic pain have more problems with sleep. Folks with sleep problems have more pain.

Now what does the real science say? First, the more you read, you realize there is this gargantuan incongruity among studies just like the incongruity of gene expression, even between identical twins. Researchers have identified genetic expression in the neural pathways that involve sleep and pain, and mutations of these genes lead to sleep disturbance and altered pain control.

Genetic studies in mice found genes called “clock genes” that control the mice’s circadian rhythm.1 Perhaps with further study in humans, we will find that the good sleepers have “Rolex” genes and the poor ones will have “Timex” genes. (I probably will get some nastygram from the folks at Timex for this analogy but I really like their product. In fact, I have some Times watches. They actually keep better time than my Submariner. Uh oh, now I’ve made both watchmakers mad. I am not PC but at least fair in my horological incorrectness.) This really is very interesting and may likely shed light in the near future on why some people are destined for the pain clinic and some are not.

Another study to support this contention was on restless leg syndrome in which researchers found from epidemiologic genetic mapping there was a place on chromosomes 12 and 14 that made folks susceptible to the disease.2 (Is restless leg syndrome really a disease? Sometimes it is nothing more than a common peroneal nerve entrapment but I guess anything is a disease now. I have Failure To Meet Deadlines Disease. We call it FTMDD in the lab.) What the authors also discovered was that geography could play a role in the genetic expression of restless leg syndrome as there was a 10 percent incidence in Eastern Canada in comparison to an incidence of 2.5 percent throughout the rest of the world.

We spend about a third of our lives sleeping. Insomniacs spend maybe a little less. That is a lot of time consumption of a human’s life not to know more about it.

So what is sleep, really? Well, first it is complex and made up of rapid eye movement (REM) and non-REM phases with four levels of non-REM and one level of REM. You will die without sleep. Studies of sleep deprivation in fruit flies and mammals have proven that.3 Sleep really is genetic and researchers have discovered that a single gene mutation in the fruit fly can reduce the time it sleeps by more than half.4 Gene mutation also contributes to major sleep disorders.3

Recognizing The Impact Of Sleep On Pain Treatment

So if sleep is genetic, one may ask, “What can I do to help my post-op patient sleep?” The simple answer may be to just give them 5-10 mg of zolpidem tartrate, that cute little GABA agonist, but that doesn’t give a true overall perspective. By the way, in January, the FDA recommended lowering the dose of zolpidem (Ambien, Sanofi Aventis) from 10 mg to 5 mg for women and from 12.5 mg to 6.25 mg for the extended release.5 But not so fast, Rx writer.

Kern Olson, PhD, is a pain psychologist at the Oregon Health and Science University Pain Management program. He states: “My own clinical experience with adults confirms a dual presentation of pain and sleep disorders occurs quite often with an estimated incidence of 60 percent to 80 percent.”6 So what this means is that nearly all of our patients on whom we operate, or at least the huge majority, are likely to have a sleep disturbance. Maybe we should start spending some time thinking about this or maybe we should really sleep on it.

Sleep is complex but it is categorized neatly based on brain waves from the electroencephalography (EEG). Light sleep is composed of Stage I and II, and deep sleep is stage III and IV. Then we get into REM sleep. The ideal sleeper goes nicely from Stage I to II, then to III and IV, and then into REM. Each cycle lasts about 90 minutes and if you are lucky, you will get four to six sessions of REM every night. The length of time spent in REM increases throughout the night, providing you do not have some type of arousal such as pain.1

Researchers have discovered that patients in chronic pain have an imbalance in their stages of sleep, spending nearly all their nodding in I and II, and very little in III and IV (deep sleep).6 Now if you want to destroy patients’ REM, give them an opiate.1 Interestingly, opiates also mess up the non-REM sleep.

This is very problematic for the practitioner. The opiate controls the pain and interrupts sleep. Sleep mitigates pain. Pain interrupts sleep. It is a difficult balance indeed.

I’m starting to nod off now. I love this bench seat. Before I drift off to level I, I just want to give you a laundry list of why sleep is so important. Sleep provides for energy conservation, reduces the oxidative stress of free radicals you built up during the day, builds your immune system and allows for neural plasticity, which aids learning, memory and protein synthesis. Protein synthesis? Yes, sleep has been shown to increase the expression of genes.1 Lucky Brand, of course.

References

1. Lavigne G, Sessle BJ, Choiniere M, Sja PJ (eds.). Sleep and Pain, first edition. IASP Press, Seattle, 2007, p.5-6.
2. Bonati MT, Ferini-Strambi L, Aridon P, Oldani A, Zucconi M, Casari G. Autosomal dominant restless legs syndrome maps on chromosome 14q. Brain. 2003; 126(Pt 6):1485-1492.
3. Bastien CH, Morin CM. Familial incidence of insomnia. J Sleep Res. 2000; 9(1):49-54.
4. Nall AH, Sehgal A. Small molecule screen in adult Drosophila identifies VMAT as a regulator of sleep. J Neurosci. 2013; 33(19):8534-40.
5. Available at www.medscape.com/viewarticle/777431 .
6. Olson KA. Pain and Sleep: A Delicate Balance. In: Practical Pain Management, volume 13: Vertical Health; 2012.

Comments

Your well done article in Practical Pain Management on neuroma decompression brought attention to innovators in the field who leave the confines of podiatry generated material. Finally, a podiatrist who looks outside the foot. Sleep anomalies directly impact the adrenal hypothalamic pituitary axis and failure to review sleep patterns can be perilous in pain patients, especially those patients suffering CRPS, malignancies or other pain generators. Thanks for pointing out the foot IS attached to the often podiatric-ly ignored body.

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