Pain: A Bridge Linking Anesthesiology and Sleep Research

FOCUSING ON SLEEP IN RELATION TO ANESTHESIA AND PAIN. I thank Editor-in-Chief, Thomas Roth, for the invitation to serve as guest editor. Particular thanks go to the authors and their reviewers for contributing to this thematic issue. The emerging dialog concerning sleep, anesthesia, and pain is a recently appreciated research opportunity. The novelty represented by the articles in this issue of Sleep is easily illustrated. For example, from Volume 1 in 1978 to October 2000, Sleep has published about 15,440 pages. These pages comprise 1669 articles in which “pain” appears four times as a title word. In addition to this special issue, the recent interest in sleep as it relates to pain and anesthesia spans from outstanding Ph.D. thesis1 to international symposia.2,3 Effective analgesia and pain management will become increasingly relevant to clinical and basic sleep researchers. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) published Pain Assessment and Management Standards in 1999, and in 2001 all accredited health care organizations will be required to comply with those standards.4 Compliance will include documenting the efficacy of pain treatment plans and educating patients and their families about pain. The close but inverse relationship between sleep and pain means that compliance with the JCAHO standards presents novel investigative and educational opportunities for sleep research. The JCAHO standards can be downloaded at URL (www.jcaho.org/standard/pm_ac.html#ri127). Pain is a complex psychophysiological experience produced by nociceptive stimuli. Leading textbooks on pain management note that sleep disruption is a key complaint of patients experiencing pain.5 From a longer evolutionary perspective, the mutually exclusive relationship between pain and normal sleep has existed throughout hominid development. Contemporary humans are indistinguishable from Homo sapiens of 50,000 years ago,6 so the neurobiology of sleep and pain must have a common evolutionary history. Thus, there is both a clinical relevance and a biological foundation for combining studies of sleep and pain. Two articles in this issue present data characterizing the mechanisms through which sleep alters nociception (Mason) and spinoreticular sensory processing (Soja). Anesthesiology, similar to sleep medicine, is a relatively recent development. Oliver Wendell Holmes is credited with the term “anesthesia” but patients commonly are informed that anesthetic drugs will put them to sleep. Anesthesiologists recognize that this use of “sleep” is only metaphoric.7 While sleep and anesthesia do share a number of similar traits, Table 1 emphasizes that sleep and anesthesia are distinctly different states.8 In 1999 general anesthesia was delivered 15.7 million times in the United States9 yet in no case do we understand exactly how the brain causes states of general anesthesia.10 Neural systems that evolved to generate traits characterizing sleep are likely to play a key role in generating anesthetic states.8 The article by Antognini in this issue shows how efforts to understand the mechanism of anesthesia must specify drug action at different levels of the brain and spinal cord. Opioids have been used for medicinal purposes by Eastern cultures since antiquity. Opioids still provide the most commonly used pharmacological tool for the clinical management of pain. Unfortunately, opioids have a number of unwanted side effects including inhibition of rapid eye movement (REM) sleep.11,12 Independent of pain, opioids disrupt sleep.13-15 The article by Cronin focuses on non-opioid factors contributing to post-surgical sleep disruption. Another opioid side effect considered in this issue by Rose et al., is impairment of immune function and host defense.16,17 Opioid actions on immune function may be direct and/or be secondary to the impairment of immune function known to be caused by sleep deprivation.18 Elucidating the mechanisms of opioid action is another opportunity for sleep research. Opioids decrease cholinergic neurotransmission in pontine regions regulating sleep19 and endogenous opioids have been suggested to contribute to regulation of electrocortical activity.20 Endogenous opioids modulate ventilation21 and postsynaptic inhibition of lumbar motoneurons.22 Although endogenous morphine now is recognized as a key signaling molecule,23 opioid actions on sleep regulating neurons remain poorly understood. In this issue, Tanase et al. show that opioid and adenosine agonists interact to activate G proteins in brain regions regulating sleep and nociception. In November 1999, the U.S. Institute of Medicine (IOM) released data showing that medical errors are a leading cause of death and injury. This report indicated that more people in the U.S. die from medical mistakes each year than from highway accidents, breast cancer, or AIDS.24 During the early 1950s, about the same time that REM sleep was discovered, the potential for harm from anesthesia was several times greater than the odds of death from polio.25 Today, anesthesiology has become so safe that deaths resulting from anesthetics delivered in the operating room have fallen to about 1:250,000.26 Continued advances in monitoring anesthetic depth will likely produce further improvements in patient safety and comfort. Some anesthesiologists, similar to some sleep researchers, are interested in ways to achieve “higher throughput.” Most patients are anesthetized without electroencephalographic (EEG) monitoring. Analogous