In my last column I used the ancient metaphor from Homer's Odyssey of being caught between the two monsters of Scylla and Charybdis to describe the predicament of contemporary physicians treating chronic pain. These clinicians are, to use the more modern phrase, between a rock and a hard place when trying to relieve pain in patients while avoiding the harm of aiding and abetting addiction. After reviewing the contradictory regulatory, public health, and ethical messages bombarding already harried physicians, I suggested that psychiatrists might be the ideal pilots to navigate a compassionate and competent course between the beast of pain and the vortex of addiction. In this column, I provide some directions for surviving the straits of pain management in an era of near epidemic prescription drug abuse. Four major landmarks derived from contemporary scholarship in public policy, neuroscience, pharmacology, and epidemiology can guide that journey.
The first signpost is the recognition so poignantly captured in Emily Dickinson's poem that was used as the epigram for this essay—pleasure and pain are not the opposites of conventional thinking but have an intimate and deep affinity that intensifies the agony of the patient and complicates care by the clinician. While mystics and poets have always intuitively understood this hidden kinship, neurobiologists are increasingly explaining the underlying common pathology. The most fundamental fact is that nearly all drugs of abuse also have some medicinal, generally analgesic, properties.1 Ironically, the history of drugs of abuse from Hippocrates onward is a story of substances being touted as miracle cures to treat pain, fatigue, malaise, and a host of other nebulous but quotidian human illnesses, with the dark side that destroys lives only gradually being revealed, followed by protective regulation.2 The political debate about medical marijuana in many respects recapitulates earlier controversies surrounding alcohol, cocaine, morphine, amphetamines, and even heroin.3 Psychiatry, as the specialty that is trained to bridge biology and spirituality, public health, and clinical medicine, is in the most optimal position to take a middle way between opiophobia and the irresponsible prescription of narcotics.
The shared neuroanatomical substrate of pain and addiction constitutes the second point of orientation. The heroin addict in the proverbial back alley who is injecting to obtain euphoria or to stave off withdrawal, and the executive who is in an ICU receiving intravenous morphine after coronary artery bypass surgery, are both undergoing activation of the dopamine- mediated, reward-laden mesolimbic pathways.4 Positron emission tomography scans of the opioid receptors of both individuals will indistinguishably light up with bright color in the amygdala and locus coeruleus. The ever-growing sophistication of psychiatrists as neuroscientists enables us to appreciate the clinical implications and applications of this rapidly progressing area of discovery.
The third marker to follow when traversing the territory of pain and addiction can be recognized not only from personal experience but also from clinical practice—stress (however ill-defined), sleep disorders, depression, and anxiety all exacerbate pain and reduce both natural pain tolerance and the efficacy of pain-relieving interventions.5 Epidemiology tells us these same psychological disturbances are also risk factors for addiction, highlighting the important role psychiatrists and other mental health clinicians have to play in the management of pain and co-occurring disorders.6 Duloxetine (Cymbalta) is the first medication to be approved for the "physical symptoms of depression"7 and its very real utility in comorbid pain and depressive conditions is an example of the underused potential of many of the adjunctive medications commonly used in psychiatry, such as anticonvulsants. As a whole, the developments outlined in this column are tantamount to a minor paradigm shift from the established division of pain and addiction as separate silos to Venn diagrams of overlapping human afflictions (Figure).
This new conceptual configuration of pain and addiction was codified in a groundbreaking 2001 collaboration of the American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine to generate consensus definitions related to the use of opioids for the treatment of pain.8 In contrast to earlier DSM and other classification systems, this document is an implicit acknowledgment that withdrawal, tolerance, and dependence are not the categorical hallmarks of addiction once postulated and are still too often misused to stigmatize and deny legitimate care.
A fourth compass point follows on the third and is known by most clinicians working in addiction or pain medicine—persons with substance abuse disorders tend to have lower pain thresholds and tolerance for physical and psychic pain. Experimental evidence supports this empirical observation; Compton and colleagues9 showed that compared with controls, patients taking methadone (Dolophine, Methadose) have a lower tolerance to cold pressor tests. The clinical corollary of this is that a person addicted to heroin who is admitted to a hospital for an incision and drainage of shooter's abscess is very likely not drug-seeking when he or she insistently and consistently reports being in terrible pain, despite being given what would be considered more than adequate analgesia.
The fourth and final area of guidance for traveling between pain and addiction is a synopsis of all the others. Hyperalgesia is a relatively nascent phenomenon, which gives proof to the wisdom of the 16th-century philosopher-physician Paracelsus: "Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy." A complex and not yet completely understood process, hyperalgesia describes the increased pain sensitivity resulting in decreased potency of analgesia that unfortunately seems to accompany much chronic opioid administration. The mechanism is theorized to be one of N-methyl-d-aspartate-mediated neuroplastic changes in opioid receptors and may also undergird tolerance.10
This blurring of the lines of pain and addiction first surfaced in Weisman's now well-known concept of "pseudo-addiction" to designate behaviors (such as taking too much medication or needing early refills) that might appear to be aberrant signs of addiction but are actually plaintive attempts to assuage inadequately controlled pain.11 Alford and colleagues12 added 2 other allied but less familiar terms to assist clinicians in further evaluating the motivations of patients with chronic pain. The first is a reframing of "drug-seeking" actions as forms of "therapeutic dependence," in which patients with adequate pain relief fear an onset of withdrawal symptoms or recurrence of nociception should they run out of or be refused medications. I frequently see this in patients who call before their prescription refills are due because they are concerned about holidays, physician unavailability, or the capriciousness of postal delivery. The second term is "pseudo-opioid resistance," which refers to continued complaints of pain despite appropriate analgesia, driven by anxiety regarding the cessation of what is now adequate treatment. Just a few weeks ago, I had a grandfather throw his crutches at me when his morphine was once again bureaucratically delayed. Even the most well-meaning practitioner will lock up his or her prescription pad when confronted with these predictive signs of trouble unless an honest and open conversation with the patient discloses prior negative experiences in obtaining pain treatment, which, unlike in true compulsive drug abuse, respond to reassurance and reason.
A final tool that may be the most useful in handling the challenge of pain and addiction is the partial opioid agonist buprenorphine (Suboxone, Subutex), approved in 2003 for the treatment of opioid dependence.13 Clinicians should be aware that the use of sublingual formulations of buprenorphine for off-label treatment of pain outside the context of opioid dependence has not received FDA approval. Waivered physicians can safely and effectively use this medication to treat illicit and prescription opioid addiction in the medical mainstream of their offices.14 Buprenorphine is a promising tool for treating comorbid pain and addiction as well as for treating traditional patients with dual diagnoses.15 Cicero and Inciardi16 showed that buprenorphine had far less potential for abuse than methadone or oxycodone (Endocodone, OxyContin, Roxicodone).
Psychiatrists are ideally suited to ferret out and fruitfully engage the multidetermined motivations and often subconscious intentionality of patients and providers struggling with issues of pain, depression, anxiety, possible misuse, and potential abuse of the most powerful drugs ever known. During our training and careers we have been taught the psychodynamic skills to identify and sublimate the transference and countertransference that bedevil substance abuse and chronic pain. Mental health professionals of all stripes encounter Gordian medical-legal dilemmas on a regular basis and have internalized the ethical attitudes required to restrain the often-disabled autonomy of the stricken patient to prevent harm to individuals and society alike.
The final instructions for psychiatric sailors come from Odysseus, who was so intent on not being engulfed in the obvious whirlpool of addiction that he did not discern the more subtle threat of pain and, not regarding the mutual dangers with equal vigilance, sacrificed members of his crew. "Sallow fear seized the men. We looked toward her in fear of our destruction. Meanwhile Scylla snatched off of the hollow ship six of my companions who were mightiest in strength."17
1. DuPont RL. The Selfish Brain: Learning from Addiction. Washington, DC: American Psychiatric Press; 1997.
2. White WL. Slaying the Dragon: The History of Addiction Treatment and Recovery in the America. Bloomington, Ill: Chestnut Health Systems/Lighthouse Institute; 1998.
3. Annas GJ. Jumping frogs, endangered toads, and California's medical-marijuana law. N Engl J Med. 2005; 353:2291-2296.
4. Fields HL. Understanding how opioids contribute to reward and analgesia. Reg Anesth Pain Med. 2007;32:242-246.
5. Compton P, Gebhart GF. The neurophysiology of pain and interfaces with addiction. In: Graham AW, Schultz TK, Mayo-Smith MF, et al, eds. Principles of Addiction Medicine. 3rd ed. Chevy Chase, Md; American Society of Addiction Medicine; 2003:1385-1404.
6. Fishbain DA, Cutler RB, Rosomoff HL, Rosomoff RS. Comorbid psychiatric disorders in chronic pain patients with psychoactive substance use disorders. Pain Clinic. 1998;11:79-87.
7. Delgado PL. Common pathways of depression and pain. J Clin Psychiatry. 2004;65:16-19.
8. American Academy of Pain Medicine, American Pain Society, American Society of Addiction Medicine. Definitions related to the use of opioids for the treatment of pain. 2001. Available at: http://www.ampainsoc.org/advocacy/opioids2.htm. Accessed October 3, 2007.
9. Compton P, Charuvastra VC, Kintaudi K, Ling W. Pain responses in methadone-maintained opioid abusers. J Pain Symptom Manage. 2000;20:237-245.
10. Pud D, Cohen D, Lawental E, Eisenberg E. Opioids and abnormal pain perception: new evidence from a study of chronic opioid addicts and healthy subjects. Drug Alcohol Depend. 2006;82:218-223.
11. Weissman DE. Understanding pseudoaddiction. J Pain Symptom Manage. 1994;9:74.
12. Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med. 2006;144: 127-134.
13. Johnson RE, Fudala PJ, Payne R. Buprenorphine: considerations for pain management. J Pain Symptom Manage. 2005;29:297-326.
14. Loxterkamp D. Helping "them": our role in recovery from opioid dependence. Ann Fam Med. 2006;4:168-171.
15. Gerra G, Leonardi C, D'Amore A, et al. Buprenorphine treatment outcome in dually diagnosed heroin dependent patients: a retrospective study. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:265-272.
16. Cicero TJ, Inciardi JA. Potential for abuse of buprenorphine in office-based treatment of opioid dependence. N Engl J Med. 2005;353:1863-1865.
17. Homer. The Odyssey. Cook A, ed. New York: Norton; 1967.