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19 Articles in Volume 14, Issue #9
10 Must Have Devices for Your Practice
1. Extracorporeal Shockwave Therapy
2. Pulsed Electromagnetic Fields
3. Class IV Laser
4. H-Wave Electrotherapy
5. Interferential Current Therapy
6. Class IIIb Cold Laser-Auriculotherapy
7. Shortwave Diathermy
8. Microcurrents
9. Infrared Phototherapy
10. Transcutaneous Electrical Neuromuscular Stimulation
Pain and Sleep: Understanding the Interrelationship
The Role of Endogenous Morphine and Nitric Oxide in Pain Management
Treating Pain in Patients With Chronic Kidney Disease: A Review of the Literature
Notalgia Paresthetica: An Enigmatic Condition
Preparing Patients Taking Sublingual Buprenorphine to Treat Addiction for Surgery
Editor's Memo: PAINWeek Going Forward Together
Introducing Practical Pain Management’s Newest Editorial Board Members
Ask the Expert: What are the products to prevent NSAID-related peptic ulcers?

Pain and Sleep: Understanding the Interrelationship

There is a growing awareness that sound restorative sleep is important to allow people to cope. Recent evidence indicates that pain and sleep have a reciprocal, interdependent relationship, and that poor sleep can predict pain and compound the pain experience in certain conditions. Therefore, it is clinically important for all pain providers to assess sleep quality for all patients living with chronic pain.
There is a growing body of research that explores the interrelationship between pain and sleep.1,2 Pain is a signal of bodily harm, and sleep is a behaviorally regulated drive that helps maintain homeostasis. If homeostasis is compromised by pain that results in sleep disruption, negative consequences will impact health and well-being. 


Unidirectional/Bidirectional Effect of Sleep

Do poor sleep patterns influence the development of future chronic pain? To answer this question, Finan et al selected 17 well-designed studies.2 They included 3 large longitudinal studies ranging from 1 to 12 years that indicate that elevated insomnia symptoms increase the risk of headache.4-6 It is important to note that the research was selective to tension-type headache and not migraine. Another population study of 15,350 Norwegian women found that sleep disorders predicted the development of fibromyalgia 10 years later.7 The authors of this study estimated that two-thirds of the patients in the sample who were diagnosed with fibromyalgia had preexisting sleep problems. Finan concluded that sleep problems increase the risk of chronic pain in pain-free individuals, worsens the long-term prognosis of existing headache and chronic musculoskeletal pain, and influences daily fluctuations in clinical pain. Conversely, they also mention that good sleep appears to improve the long-term prognosis of individuals with chronic pain conditions.2

Next, Finan et al evaluated recent prospective studies assessing the bidirectional effects of sleep and pain. They proposed that a trend has emerged suggesting that sleep disturbances may predict pain to a greater degree than pain predicts sleep problems. Their broad analysis of data suggests that sleep and pain appear to be a reciprocally related, but a closer analysis suggests that poor sleep may have a stronger influence on the experience of chronic pain.2

The growing body of research strongly suggests, at the clinical level, that sleep quality should be included in the initial assessment of all patients who present with chronic pain. In my opinion, this is not a difficult task. For the past 25 years, I have included interview questions that assess the quality of a patient’s sleep. If I determine that a sleep problem exists, I will ask the patient to fill out a sleep log that covers 1 week. Further, I will administer the Epworth Sleepiness Scale (ESS).8 This scale is easy to administer, takes 10 minutes to fill out, and provides additional information to help rule out whether a sleep disorder exists. I include this information in my report back to the referring physician, so they can decide if a formal sleep study is indicated. The ESS can be obtained free of charge online.8 

Prevalence of Sleep Problems

One finding consistently stands out based on large community studies from around the world—chronic pain appears to be the main reason why patients sleep poorly (difficulty initiating sleep, disrupted sleep, early morning awakenings, and unrefreshing sleep). Because there has been no uniform methodology in pain/sleep epidemiological studies, the estimated prevalence of sleep problems is quite variable, ranging from 23% in Europe to 89% in the United States.9 Table 1 provides a summary of sleep disturbance findings in patients with chronic pain. Research supports the fact that pain and sleep are interrelated, and the relationship is very complex due to the many factors that can influence both processes.


The Nature of Sleep

Since sleep and pain are reciprocally related, both bidirectionally and unidirectionally, it is important to understand the nature of sleep—the types and patterns of sleep, how sleep is generated by the brain, and the role that sleep plays in an individual’s overall functioning. It is necessary to understand the mechanics and physiology of sleep to be able to appreciate the interrelationship of pain and sleep on physical activity and behavior.

What is sleep and why is it so important to the patient with pain and in the treatment of pain? The average individual spends a considerable amount of time sleeping. About one-third of our life is spent in this endeavor. In the past, it was thought that sleep was quiet time for the brain and body to recuperate from the demands of the day. Recent sleep research, however, has refined that notion and has discovered that sleep is a carefully controlled and highly regulated series of states that occur in a cyclical fashion each night. Sleep is critical in maintaining homeostasis, which reinforces the fact that we need uninterrupted sleep to survive and cope with the demands of every day life. Quality sleep is crucial for the pain patient who deals with the additional demands that pain imposes on maintaining homeostatic balance.

Sleep is divided into 2 separate and distinct states: rapid eye movement (REM) and non-REM sleep. Both are equally important in maintaining physical and mental homeostasis. When a patient undergoes a sleep study, brain wave activity is monitored by an electroencephalogram (EEG). This information helps the sleep physician determine the quality and quantity of both REM and non-REM sleep.

Non-REM Sleep

Non-REM sleep is divided into four stages: Stage I and II are considered “light sleep,” whereas Stages III and IV are considered “deep sleep.” As we progress from Stage I to Stage IV, brain wave activity slows down, as measured by the EEG, from active beta-wave to slow delta-wave sleep. Non-REM sleep is important for both brain and body restoration.

REM Sleep

REM sleep is considered “active sleep” because brain activity and EEG patterns are similar to brain activity when we are awake. During REM sleep, our muscle systems are inactive, unlike heart rate, breathing, and blood pressure, which are highly variable. Also during REM sleep, we experience story-like dream activity. In my opinion, it is our ability to dream that is critical in maintaining mental homeostasis. Dreaming allows us to deal with the demands of life, and when REM sleep is disrupted, mental disturbances can result. I will revisit this issue later when pain and sleep medicines are reviewed.

Sleep Cycles

As mentioned earlier, sleep stages are cyclical. REM and non-REM sleep alternate throughout our time asleep (Table 2). According to Carskadon and Dement, the first half of the night usually is non-REM sleep (Stages III and IV), with brief REM sleep periods.10 As sleep progresses, Stages III and IV decrease and Stage II becomes more evident (non-REM). REM sleep becomes longer, reaching the maximum during the last third of the night. REM sleep periods can range from 4 to 6 minutes, depending upon the length of sleep. Sleep cycles change throughout the total sleep time, with an approximate length of 90 minutes. Healthy adults spend about 75% to 80% of sleep time in non-REM sleep and about 20% to 25% in REM sleep. It is important to appreciate how fragile and critical this cyclic progression (Figure 1) is on our ability to cope with life’s demands and maintain our mental and physical balance.



Sleep Studies

My experience working with a sleep center as a behavioral consultant allowed me to examine sleep studies of patients who experienced chronic pain. I observed consistent patterns of excessive Stage I and Stage II sleep, with little or no Stage III or Stage IV slow delta-wave sleep. This observation made sense to me because pain patients will experience painful episodes throughout the night when they roll over or spend too much time in one position. This observation is probably more relevant to myofascial and joint pain compared to some neuropathic pain conditions. Neuropathic pain can occur independent of movement and is usually described as a burning sensation.

If the sleep cycle is interrupted by pain, the patient will cycle to Stage I or II and will not progress to deeper, slow delta-wave sleep. This pattern will repeat itself throughout the night, which results in a continuous sleep deficit that produces a state of constant daytime fatigue. As days of fatigue accumulate, additional stress is experienced and the patient’s pain threshold will be negatively compromised. In addition, if the pain patient does not sleep well, they will usually spend more time in bed, mostly in light or non-restorative sleep. This pattern also is found in depressed patients with or without pain.

Early in my career, I was fortunate to attend a week-long sleep workshop conducted by Peter Hauri, PhD. Dr Hauri is no longer with us, but during his long career as a sleep psychologist, he was considered a preeminent authority on sleep disorders. For those interested in a comprehensive sleep program, I highly recommend his book No More Sleepless Nights. There also is a workbook available that complements his approach to improving the quality of sleep.11

Neurological Control of Sleep

Recent findings suggest that specific brain regions play a critical role in sleep regulation, as they do in the pain regulation.12 Saper et al found that damage to the anterior hypothalamus caused severe insomnia.13 These findings suggest that the hypothalamus is involved in controlling both waking and sleeping states, as well as in the control of pain. Further, Saper’s work pointed out that the hypothalamus and the basal forebrain generate non-REM sleep. It is pertinent that both of these areas contain active gamma aminobutyric acid (GABA)-
ergic neurons, which have an important role in the control of pain and sleep. These GABAergic neurons are sensitive to changes in body temperature that trigger a “sleep switch” that turns sleep on and off. 13 These findings suggest that GABA is related to both sleep and pain at the neurophysiologic level. REM sleep is controlled primarily by the brain stem, which also overlaps with the neural control of pain.

Additional research has indicated that dopamine may be involved in sleep regulation. Dopamine also is involved in the regulation of pain and mood. Dysregulation of the dopamine system may lead to persistent insomnia or sleepiness.14,15 The above research findings suggest that pain and sleep are related to dopamine levels. This association has important implications for pharmacologic treatment of patients who experience both pain and disrupted sleep.

Factors Influencing Sleep


Opioids. The most frequently prescribed medicines for the management of chronic pain are opioid-based, both short-acting and long-acting formulations. However, a growing body of research has repeatedly demonstrated that opioids disrupt sleep architecture and inhibit REM sleep.16,17 As mentioned earlier, the balance between REM and non-REM sleep is critical in maintaining homeostasis. REM sleep is especially critical in maintaining optimal mental health. Consistent research findings have suggested that sleep disruption is an unwanted side effect of opioid therapy that results in a lower pain threshold.17,18 Therefore, clinicians should re-evaluate the use of opioids in patients with insomnia and pain. This may present challenges, as the undertreatment of pain can also result in difficulty with sleeping.

Non-steroidal anti-inflammatory drugs (NSAIDs). Unfortunately, there are few studies examining the effects of NSAIDs on sleep in either healthy subjects or patients with chronic pain. The few studies that have examined this issue suggest that NSAIDs and acetaminophen do not appear to affect sleep architecture in healthy human subjects.19 In fact, in a small study of patients with rheumatoid arthritis who were prescribed the NSAID tenoxicam for 90 days, 50% of patients reported a reduction in joint pain, with no altered sleep architecture.20 [Editor’s Note: Tenoxicam (Mobiflex) is not available in the United States.]

Andepressants. The results of antidepressant research on pain and sleep are mixed. Some of the tricyclic antidepressants (TCAs), such as amitriptyline, suppress REM sleep.21 The serotonin reuptake inhibitors (SSRIs) also have been found to inhibit REM sleep. 21 When comparing the TCAs and the SSRIs with respect to sleep alone, the SSRIs appear to have little effect on sleep architecture excluding REM sleep, but it is unknown if they have a favorable effect on pain. Conversely, there is research supporting the use of TCAs in the treatment of neuropathic and muscle pain.22 The one antidepressant that appears to have little or no effect on either short beta-wave or REM sleep time is nefazadone (Serzone),23 the sale of which was discontinued in 2004 in the US and Canada due to a rare incidence of liver damage.

In my clinical experience as a pain psychologist, I have found that a trial of the shorter-acting TCAs at a small or homeopathic dose level (much lower than that used to treat depression) at bedtime to be helpful. By starting with a small dose (10-20 mg) of the shorter- acting TCAs, unwanted side effects are minimized. If it is initially helpful, the clinician can slowly titrate the dose upwards. Further, I have found over the years that prescribing physicians often start with too big of a dose of TCAs, which produce immediate unwanted side effects that result in the patient discontinuing the trial prematurely without fully knowing if the TCA would have been helpful. Antidepressants have an important role in contributing to the descending inhibition of the pain signal, especially in patients with comorbid depression. Therefore, based on these 2 findings, a trial of an appropriate antidepressant medicine appears warranted for the pain patient who also experiences a sleep disorder.

Antiepileptics. Recent research has supported the use of antiepileptic medicines in the treatment of neuropathic pain and other chronic pain disorders.24 It appears that some of the older antiepileptic medicines appear to have negative side effects on sleep architecture, but the newer medicines appear to have minimal or even beneficial effects on sleep quality.25 Both gabapentin (Gralise, Neurontin, Horizant, others) and pregabalin (Lyrica) have been found to increase slow wave sleep without affecting REM sleep.26

Table 3 provides a brief summary of analgesic use and subsequent effect on sleep architecture from Cairns.25


Circadian Rhythm and Neurohormones

There is a growing body of sleep research emphasizing the important role of circadian rhythms and the maintenance of homeostatic balance in sleep.13 Further, it is believed that this homeostatic drive for sleep is genetically influenced.27 Homeostatic balance is especially important for the pain patient who does not sleep well. Therefore, we need to briefly discuss the role that the circadian clock plays in influencing the quality of sleep time.

If you disrupt the circadian rhythms in humans, it will have a negative impact on maintaining homeostatic balance that includes the pain experience. Again, it is interesting to note the neural overlap between pain and the regulation of circadian rhythms and sleep by the anterior hypothalamus—more specifically, the supra chiasmatic nucleus (SCN).28

The pineal gland is regulated by the SCN. Melatonin, the primary neurohormone of the pineal gland, plays a critical role in regulating circadian rhythms. Light transmission from the retina stimulates neural signals into the anterior hypothalamus and the SCN. These signals then are relayed to the pineal gland. Brzezinski found that melatonin rises after the onset of darkness, peaks in the middle of the sleep period (between 2 and 4 AM), and then gradually falls during the second half of the night.25 In addition, melatonin has been found to induce sedation and lower core body temperature.29 The other neuromodulator that affects homeostatic sleep drive is adenosine, which is accumulated during the day and eventually activates sleep-promoting neurons.28

Even though the research is mixed on the effectiveness of melatonin, I have found in my own practice that it is helpful in promoting sleep for some patients. It is relatively inexpensive and is classified by the FDA as a dietary supplement. No serious side effects have been associated with the use of melatonin. It also should be noted that melatonin has a short half-life. Therefore, I recommend that patients try a sustained-release formulation. They should take it approximately 30 minutes before bedtime in doses ranging from 1 mg to 10 mg. Also, keep in mind that as a person ages, natural melatonin levels decrease, so age becomes an additional factor to consider. This decrease in melatonin levels, especially in the senior population, is felt to be a factor that decreases sleep quality as we age.

In 2005, the FDA approved a prescription form of melatonin ramelteon (Rozerem) for the treatment of insomnia, especially for difficulty with sleep onset. Initial research results suggest that it has a faster onset of action compared to melatonin supplements and a longer half-life.30 In one well-controlled study examining varying dose levels of ramelteon (4, 8, 16 and 32 mg), all dose levels showed significant results in lowering sleep-onset time.31

Cognitive-Behavioral Factors

There is a growing body of research supporting the role of cognitive-behavioral factors in the association between pain and sleep.2,32,33 These identified factors are: mood disturbance, activity, conditioned hyperarousal, and pre-sleep cognitive rumination. Cognitive-behavioral therapies (CBT) for pain and insomnia usually include relaxation training augmented by biofeedback, coping skills training, cognitive therapy, increasing activity levels, and goal setting. There are newer promising cognitive-based therapies that include mindfulness meditation, movement therapy, and action commitment therapy.


Additional behavioral techniques that I use in my practice when a patient is identified as having both pain and sleep issues include a thorough discussion of sleep hygiene (basic information to improve sleep quality) and the use of a sleep log. Self-monitoring of any behavior is reactive or therapeutic, and, in this case, keeping track of sleep behavior becomes part of the therapy. Another tool that has become available is a portable actigraph, which can be worn on the wrist and is fairly inexpensive. The information gained from using an actigraph can provide useful assessment information and become part of the treatment in the form of self-monitoring.

Psychophysiological Arousal

I would like to reinforce a consistent clinical feature that is common to both pain and insomnia. Psychophysiological arousal is a key component that is common in both conditions. Psychophysiological arousal is the same as sympathetic reactivity and/or clinical anxiety. When a patient is described as anxious, I usually assess sympathetic reactivity by the use of a skin temperature thermistor, which will usually reflect cooler skin readings, suggesting vasoconstriction.

If the patient is cold in the extremities at bedtime, it will take longer for the patient to fall asleep. I also have found that if the patient is cold in the extremities, they usually will report higher pain levels. Note that skin temperature and blood flow are relative. Individually, we have a physiological window that will vary depending on our level of sympathetic reactivity. I have found that skin temperatures below 80 degrees are clinically significant. Mid-80s suggest moderate sympathetic reactivity, and low-90s are ideal. If I can raise a patient’s skin temperature by a couple of degrees using relaxation therapy augmented by temperature biofeedback, the patient usually will report lower pain levels.

This finding also is true for sleep. I instruct the patient to use relaxation techniques in bed, and to check their skin thermistor for increased skin temperature. I also instruct the patient to use positive affirmations of a deep and restful sleep as they progress to a deeper state of relaxation. I encourage them to repeat the above sequence if they awake during the night. More importantly, if they can achieve more restful sleep with behavioral techniques without the use of a sleep aid (medication) they will feel an enhanced sense of self-control or self-efficacy. We are not trying to duplicate core temperature, just skin temperature, which is reflective of sympathetic reactivity.

Further, I propose that control of sympathetic reactivity should be the gold standard for all CBT therapies whether it be progressive relaxation, autogenics, self-hypnosis, or mindfulness meditation. One technique or approach may not fit all patients, so it is important to remain flexible as one explores various treatment options.

Pain and Dream Activity

There are a few published anecdotal reports from the late 19th century and early 20th century discussing the relationship between pain and dreams. These early reports focused on the sensory experiences that could occur in dreams. According to Zadia and Manzini, reference to physical pain was absent from everyday dream reports or were indirectly incorporated into the dream when generated by an external stimulus.34

Today we know that dream activity usually occurs during REM sleep, but it also can occur during other sleep stages. Research findings from sleep studies suggest that sensory stimuli applied during REM can influence dream activity. Further, these sleep studies suggest that patients who participated (over 300 dream reports) do not incorporate physical pain in their dreams. The authors conclude that based on these reports, the dreaming mind is unable to incorporate physical pain sensations.34

Recent work by Damasio explored the relationship of dreaming and consciousness.35 Damasio found that consciousness also is depressed during REM sleep. But during REM sleep, dream content can enter consciousness by learning or subsequent recall.35 In my opinion, REM sleep and dreaming are important for the pain patient in maintaining a sense of self and promoting mental homeostasis.

I have found in my clinical practice that some patients can dictate their dream activity. This can be a useful tool in helping the patient cope with their pain. I often ask the patient about the themes of their dream activity and whether they can construct positive approaches to cope with their pain on a daily basis. Relaxation therapy can be helpful in the patient’s home environment. I ask the patient to dream about some of the goals we are focusing on in therapy and how those goals can improve the quality of his or her life. In a deep relaxed state, the mind is more open, or “absorbent,” to self-directed thoughts.


It has been established that having quality sleep is critical for the pain patient to maintain mental and physical homeostasis. There is a growing awareness within the pain community that sound restorative sleep is important to allow the pain patient to cope with persistent discomfort on a daily basis. Recent evidence indicates that pain and sleep have a reciprocal, interdependent relationship. In addition, recent research has established that poor sleep can predict pain in certain conditions and that poor sleep compounds the pain experience. Therefore, it is clinically important for all pain providers to assess sleep quality for all patients living with chronic pain. And if sleep problems are diagnosed, pain practitioners should help establish good sleep hygiene practices and, when needed, prescribe treatments to help patients initiate and maintain restorative sleep.

Last updated on: May 18, 2015

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