PHILADELPHIA—Many patients’ sleep complaints are comorbid with pain disorders, and disturbed sleep can exacerbate pain, according to an overview presented at the 66th Annual Meeting of the American Academy of Neurology. Managing sleep problems can help reduce patients’ pain, but certain drugs may disrupt sleep and thus increase pain.
The literature suggests a bidirectional relationship between sleep disturbances and pain, said Alon Avidan, MD, MPH, a neurologist at the Ronald Reagan University of California, Los Angeles, Medical Center. A 2011 article in the Clinical Journal of Pain showed that patients’ pain scales and pain ratings increased on the day after a night of poor sleep. In addition, a day of increased pain was followed by a night of poor sleep.
A study published in 2009 found a direct association between impaired sleep and reduced activation of inhibitory pain pathways. Furthermore, data from animal and human studies suggest that sleep deprivation leads to hyperalgesic changes.
“Morning headaches are three times more common in patients with obstructive sleep apnea [OSA] syndrome,” said Dr. Avidan. “Asking patients about sleep, choking at night, snoring, waking up with a headache, and excessive daytime sleepiness is really helpful. Once you treat the underlying sleep-disordered breathing, the pain scales improve.”
Alon Avidan, MD, MPH
Certain Drugs Disrupt Sleep and May Increase Pain
Although alleviating pain may improve sleep, certain analgesics, such as opioids, can disturb sleep. Specifically, opioids reduce sleep time, decrease sleep efficiency, increase sleep latency, increase arousals, and reduce restorative slow wave sleep. Impaired sleep often increases pain and creates a need for more analgesics. Opioids also can worsen sleep-disordered breathing.
Opioids may be an appropriate treatment for pain in patients with OSA who are well managed with positive airway pressure. Patients with significant pain who may be candidates for opioid therapy should be screened for OSA with the STOP BANG Questionnaire. Patients who report snoring, daytime sleepiness, and apneic spells should undergo sleep testing. For patients with OSA who have not been tested or treated, neurologists should analyze the risks and benefits of opioid therapy, said Dr. Avidan.
Selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors (SNRIs) also degrade sleep architecture. Venlafaxine, an SNRI, significantly worsens restless legs syndrome (RLS), and many antidepressants reduce or eliminate REM sleep. But psychiatric symptoms may justify the use of these medications. “We don’t treat a sleep study. We treat a patient,” said Dr. Avidan.
Drug Classes Treat Specific Types of Insomnia
In approximately two-thirds of patients with insomnia, the condition is comorbid with another primary sleep disorder, primary medical condition, psychiatric condition, or pain. Difficulties with sleep maintenance are often related to chronic pain, nocturia, sleep apnea, and motor disturbances of sleep such as periodic leg movement disorder, which is common in patients with Parkinson’s disease or multiple sclerosis. Data show that increased pain sensitivity, which is directly attributed to disruption of sleep architecture, results when primary sleep disorders are undiagnosed or untreated.
When combined with cognitive behavioral therapy, hypnotic agents such as benzodiazepine receptor modulators (eg, zolpidem and eszopiclone) and the melatonin receptor agonist ramelteon may be suitable for the management of insomnia and target the underlying hyperarousal associated with it. Additional treatment with pain medications such as alpha-2-delta ligands may be helpful if the patient has sleep initiation insomnia in the context of RLS or painful peripheral neuropathy, said Dr. Avidan. This adjunctive therapy can manage the pain and allow for sedation.
Melatonin is considered a dietary supplement and is not regulated by the FDA. Consequently, the amount of active ingredient in a tablet of a given strength can vary widely. Although melatonin receptor agonists are more expensive, they may be more effective because the dose is regulated, and their selectivity to the endogenous melatonin receptors is greater than that of over the counter melatonin.
Treating RLS May Improve Sleep and Reduce Pain
Sleep medicines can be effective in reducing pain. In one 2012 study of patients with fibromyalgia and pain, treatment with sodium oxidate, a hypnotic medication, decreased patients’ pain scores and improved sleep, compared with placebo. The literature also indicates a high prevalence of RLS in patients with fibromyalgia. If a patient presents with rheumatoid arthritis and fibromyalgia, the neurologist should screen the patient for RLS, said Dr. Avidan. Treating RLS may also improve fibromyalgia symptoms, he added.
Three primary first-line therapies for RLS, ropinirole, pramipexole, and rotigotine, are dopamine agonists. The main side effects of dopamine agonists are impulse-control problems, sleepiness, and augmentation (ie, the spread of RLS symptoms to other body parts and the emergence of RLS symptoms earlier during the day). These side effects may emerge with long-term use, said Dr. Avidan. The other first-line therapy for RLS, gabapentin-enecarbil, is an alpha-2-delta ligand that can be helpful for RLS comorbid with pain.