OUP user menu

Opioid-Based Multimodal Care of Patients with Chronic Pain: Improving Effectiveness and Mitigating Risks

Scott Fishman MD
DOI: http://dx.doi.org/10.1111/j.1526-4637.2009.00676.x S49-S52 First published online: 1 July 2009

Chronic pain, pain that persists beyond the normal tissue healing time, is a complex neurobiologic condition requiring multimodal treatment [1]. By definition a subjectively unpleasant experience, pain is an untestable hypothesis that requires predefined functional goals against which to objectively measure progress and treatment success [2,3]. Comprehensive assessment of chronic pain is necessarily multidimensional, requiring attention across multiple biological, psychological, and social domains [4,5]. First, characterizing patient complaints and functional impairment helps define realistic treatment goals. Second, identifying objective signs, patient-reported symptoms, and phenomenology of the syndrome, from which pathophysiology may be inferred, can shape mechanism-based therapies. Third, examining psychosocial and medical comorbidities can further optimize individualized therapy. Although pain may be initiated by acute tissue damage and adaptive nociceptive signaling, it is deep in the cortical areas of the brain where chronic and maladaptive pain signals are interpreted, assigned affective meaning, and ultimately perceived [6]. Treatment, especially with opioids, requires a vigilant and transparent relationship between clinician and patient, so that each understands the challenges and responsibilities inherent in treating a complex and often debilitating condition [7]. Only by integrating this information may we, as clinicians, tailor therapy consistent with the pain profile, goals of therapy, and with the level of risk.

In this series of articles, clinicians across the continuum of care—pain specialists, primary care clinicians, nurse practitioners, pharmacists, and psychologists—share their best practices and contribute important insights into pain management. Together, we hope they provide a practical framework within which clinicians may improve their diagnostic skills and opioid-based multimodal treatment of chronic pain syndromes.

It is generally accepted that chronic pain is not a unitary phenomenon; rather, clinical and laboratory studies have shown that the pain experience is governed by multiple pathophysiologic mechanisms. Normal sensation requires an appropriate balance among inhibitory and excitatory signals; alterations in this balance likely contribute to the development of acute and chronic pain [8]. In the first article of this supplement, Charles Argoff, MD, Phillip Albrecht, PhD, Gordon Irving, MD, and Frank Rice, PhD, discuss the roles of keratinocytes and the epidermis in the modulation of neural activity. Recent studies suggest that hyperexcitable epidermal nerve endings in the periphery—typically damaged by noxious stimuli—and their neighboring keratinocytes contribute to the abnormal reorganization of the central nervous system underlying various chronic pain states [9]. Delineation of neural pathways through which pain is transduced, transmitted, modulated, and interpreted has established a cogent, yet still-emerging, rationale for multimodal therapy [8]. Still, only two multidrug studies for chronic pain have been published to date, each of which evaluated the safety, tolerability, and efficacy of regimens, combining opioids and gabapentin for patients with neuropathic pain [10,11]. The data are encouraging; the questions they raise are explored in this supplement.

Like pain and risk management in all special populations, optimizing care in older adults requires heightened vigilance [12]. As the US population continues to age—underscored by a recent report finding that nearly 40% of adults aged 65 or older experience daily pain [13]—the challenges of treating chronic pain will become increasingly common. In their article “Special Issues in the Management of Chronic Pain in Older Adults,” Patricia Bruckenthal, PhD, RN, ANP-C, M. Carrington Reid, MD, PhD, and Lori Reisner, PharmD, evaluate these challenges and their implications for treatment. Prevalence rates of noncancer chronic pain syndromes such as chronic low back pain, postherpetic neuralgia, diabetic neuropathy, osteoarthritis, osteoporosis, and other degenerative joint and disk diseases continue to rise [14]. Worse yet, older patients—and occasionally even their clinicians—believe that chronic pain is a normal consequence of aging, dismissing many pain complaints and thereby unknowingly contributing to the underassessment and undertreatment of pain [3,15]. Compounding their resignation, older patients may characterize their pain as merely an ache or discomfort rather than pain per se, an ambiguity that requires additional time and effort to elucidate [16]. Furthermore, older patients with post-stroke complications, mild cognitive impairment, or other types of age-related dementia are often noncommunicative, underscoring the need for improved assessment strategies and validated screening tools [15]. Older patients often present with medical comorbidities, requiring the clinician to consider, among other issues, potential drug–drug interactions. Age-related changes in hepatic and renal function may complicate the choice of medications, practical guidance for which is provided by the Beers Criteria [17]. Special attention also is required to manage the gastrointestinal and cardiovascular risks of nonsteroidal anti-inflammatory drugs, as well as opioid-related constipation, somnolence, and nonmedical use (misuse/abuse). Selecting appropriate medications and interventional and nonmedical therapies also requires due sensitivity to the fixed income of many older patients.

Four general principles, originally suggested by Russell K. Portenoy, MD, have been outlined to facilitate the decision-making process for opioid-based therapy, and include an evaluation of the following: 1) conventional treatment for the pain syndrome; 2) risk–benefit ratios of all potential interventions; 3) impact of the potential adverse consequences of prescribing opioids; and 4) risk of nonmedical use [18].

Careful consideration of these and related issues may improve appropriate selection of patients for opioid therapy. However, there is little, if any, evidence supporting this selection process, nor is there guidance on how best to initiate, titrate, and maintain these medications for maximal analgesia and minimal risk. For instance, surprisingly few studies have directly compared the relative efficacy of short- and long-acting formulations of opioids [19–22]. Perry G. Fine, MD, Gagan Mahajan, MD, and Mary Lynn McPherson, PharmD, in their article “Long-Acting Opioids and Short-Acting Opioids: Appropriate Use in Chronic Pain Management,” discuss clinician reliance on judgment and experience in formulating opioid-based therapeutic plans. The authors explore the respective roles of short- and long-acting opioids and best practice recommendations for their use in combination with other modalities.

As part of a multidisciplinary, multimodal regimen, opioids have helped some patients with noncancer pain syndromes achieve clinically meaningful analgesia and important functional gains [11]. Still, increased opioid prescribing has led to a correspondingly steep increase in their nonmedical use [23]. Most alarmingly, as discussed by Aaron M. Gilson, MS, MSSW, PhD, and Paul G. Kreis, MD, in their article “The Burden of the Nonmedical Use of Prescription Opioid Analgesics,” data from the National Survey of Drug Use and Health (NSDUH), the Drug Abuse Warning Network (DAWN), and other epidemiologic sources show that adolescents are the fastest growing subpopulation of recreational abusers. Despite its heterogeneity and limitations, the data clearly demonstrate the magnitude and far-reaching impact of nonmedical opioid abuse on patients, prescribers, payors, and public health [24]. Risk mitigation strategies are urgently needed. Differential diagnosis of patient behavior has become an essential, if still emerging discipline that requires ongoing assessment, particularly of patient motivation, and may help discriminate among such phenomena as abuse, addiction, pseudoaddiction, and tolerance [25]. Artful use of prescription monitoring programs may help monitor potential diversion as well [26].

As the prevalence of chronic pain and nonmedical opioid use continue to grow, a significant clinical burden increasingly will fall upon primary care practitioners. Steven D. Passik, PhD, and Pamela Squire, MD, CCFP, in their article “Current Risk Assessment and Management Paradigms: Snapshots in the Life of the Pain Specialist” share their views on this important development, as well as on resolving the dilemmas presented by opioids in chronic pain management. Using case studies, they illustrate best practices in risk stratification, differential diagnosis, and the initiation, maintenance, and discontinuation of opioid-based plans.

Douglas L. Gourlay, MD, MSc, FRCP, FASAM, and Howard A. Heit, MD, FACP, FASAM, in their thought-provoking article “Universal Precautions Revisited: Managing the Inherited Pain Patient”, discuss universal precautions, and the responsibilities and trust required to optimize care. Benefits of triaging patients into low-, medium-, or high-risk groups are evaluated as well. Interestingly, the authors apply their pain and risk management approaches to the “inherited” pain patient, an increasingly important medical and societal issue [27]. Many of the prevailing challenges in pain medicine are addressed in this article, including interpretation of results of urine drug screening; current prescribing regulations and the importance of “pill-load” in risk mitigation; longitudinal monitoring for opioid-induced hyperalgesia, and endocrine and immune dysfunction; when and how to rotate, taper, and discontinue opioids; and opioid treatment agreements and “termination of controlled substances” agreements.

In the final and forward-looking article, “Update on Abuse-Resistant and Abuse-Deterrent Approaches to Opioid Formulations,” Lynn Webster, MD, discusses investigational short- and long-acting opioid formulations designed to reduce problematic opioid consumption. Currently, the partial opioid-receptor agonist buprenorphine is available in the United States for use with or without naloxone (Suboxone and Subutex, respectively) for the treatment of opioid dependence. Data suggest that buprenorphine and its combination formulations have low rates of abuse compared with hydromorphone [28,29]. Currently available formulations of OxyContin were once thought to be less easily abused, until epidemiologic and clinical studies established that abusers could easily defeat the controlled-release mechanism and experience euphoria from the significant (38%) immediate-release component [29–31]. Clinical and preclinical studies are presently underway for the development of abuse-resistant opioid formulations that employ physical barriers to withstand chemical and physical challenges, and abuse-deterrent formulations that include naltrexone, niacin, or other pharmacologic agents to discourage inappropriate use [32–35]. Upon approval, epidemiologic studies will be needed to determine the impact of these drugs on the extent of nonmedical opioid use across the United States.

This series of articles makes important contributions to the pain medicine literature. The long-term opioid-based care of patients with cancer-related and noncancer pain syndromes presently surpasses available supporting evidence [36]. Anecdotal reports, case studies, and the sound clinical judgment of pain and primary care clinicians predominate the available evidence. Robust and well-designed clinical studies investigating multimodal strategies are needed to supplement practice-based evidence and to help clinicians individualize care and minimize risk.


The author has no disclosures to report.

This supplement has been sponsored by an unrestricted grant from King Pharmaceuticals®, Inc. Editorial support was provided by Megan Fink, Ariel Buda-Levin MS, John Lapolla MS, Maggie Van Doren PhD, Jim Kappler PhD, as well as Innovex Medical Communications.


View Abstract