Over the past two decades, as the prevalence of chronic pain and health care costs have exploded, an opioid epidemic with adverse consequences has escalated. Efforts to increase opioid use and a campaign touting the alleged undertreatment of pain continue to be significant factors in the escalation. Many arguments in favor of opioids are based solely on traditions, expert opinion, practical experience and uncontrolled anecdotal observations. Over the past 20 years, the liberalization of laws governing the prescribing of opioids for the treatment of chronic non-cancer pain by the state medical boards has led to dramatic increases in opioid use. This has evolved into the present stage, with the introduction of new pain management standards by the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) in 2000, an increased awareness of the right to pain relief, the support of various organizations supporting the use of opioids in large doses, and finally, aggressive marketing by the pharmaceutical industry. These positions are based on unsound science and blatant misinformation, and accompanied by the dangerous assumptions that opioids are highly effective and safe, and devoid of adverse events when prescribed by physicians. Results of the 2010 National Survey on Drug Use and Health (NSDUH) showed that an estimated 22.6 million, or 8.9% of Americans, aged 12 or older, were current or past month illicit drug users, The survey showed that just behind the 7 million people who had used marijuana, 5.1 million had used pain relievers. It has also been shown that only one in 6 or 17.3% of users of non-therapeutic opioids indicated that they received the drugs through a prescription from one doctor. The escalating use of therapeutic opioids shows hydrocodone topping all prescriptions with 136.7 million prescriptions in 2011, with all narcotic analgesics exceeding 238 million prescriptions. It has also been illustrated that opioid analgesics are now responsible for more deaths than the number of deaths from both suicide and motor vehicle crashes, or deaths from cocaine and heroin combined. A significant relationship exists between sales of opioid pain relievers and deaths. The majority of deaths (60%) occur in patients when they are given prescriptions based on prescribing guidelines by medical boards, with 20% of deaths in low dose opioid therapy of 100 mg of morphine equivalent dose or less per day and 40% in those receiving morphine of over 100 mg per day. In comparison, 40% of deaths occur in individuals abusing the drugs obtained through multiple prescriptions, doctor shopping, and drug diversion. The purpose of this comprehensive review is to describe various aspects of crisis of opioid use in the United States. The obstacles that must be surmounted are primarily inappropriate prescribing patterns, which are largely based on a lack of knowledge, perceived safety, and inaccurate belief of undertreatment of pain.

Opioid Epidemic in the United States

Background Long-term opioid therapy for chronic noncancer pain is becoming increasingly common in community practice. Concomitant with this change in practice, rates of fatal opioid overdose have increased. The extent to which overdose risks are elevated among patients receiving medically prescribed long-term opioid therapy is unknown. Objective To estimate rates of opioid overdose and their association with an average prescribed daily opioid dose among patients receiving medically prescribed, long-term opioid therapy. Design Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at the time of overdose. Setting HMO. Patients 9940 persons who received 3 or more opioid prescriptions within 90 days for chronic noncancer pain between 1997 and 2005. Measurements Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes--nonfatal and fatal overdoses--were identified through diagnostic codes from inpatient and outpatient care and death certificates and were confirmed by medical record review. Results 51 opioid-related overdoses were identified, including 6 deaths. Compared with patients receiving 1 to 20 mg/d of opioids (0.2% annual overdose rate), patients receiving 50 to 99 mg/d had a 3.7-fold increase in overdose risk (95% CI, 1.5 to 9.5) and a 0.7% annual overdose rate. Patients receiving 100 mg/d or more had an 8.9-fold increase in overdose risk (CI, 4.0 to 19.7) and a 1.8% annual overdose rate. Limitations Increased overdose risk among patients receiving higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation. Conclusion Patients receiving higher doses of prescribed opioids are at increased risk for overdose, which underscores the need for close supervision of these patients. Primary funding source National Institute of Drug Abuse.

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Opioid prescriptions for chronic pain and overdose: a cohort study.

As long-term opioid therapy for chronic noncancer pain is becoming more common in community practice, rates of fatal opioid overdose have increased. Dunn and coworkers found that 51 of 9940 adults ...

https://rsds.org/wp-content/uploads/2015/02/DunnKM_AnnInternMed_2010.pdf

Opioid Prescriptions for Chronic Pain and Overdose

Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or might be different from the original underlying pain. OIH appears to be a distinct, definable, and characteristic phenomenon that could explain loss of opioid efficacy in some patients. Findings of the clinical prevalence of OIH are not available. However, several observational, cross-sectional, and prospective controlled trials have examined the expression and potential clinical significance of OIH in humans. Most studies have been conducted using several distinct cohorts and methodologies utilizing former opioid addicts on methadone maintenance therapy, perioperative exposure to opioids in patients undergoing surgery, and healthy human volunteers after acute opioid exposure using human experimental pain testing. The precise molecular mechanism of OIH, while not yet understood, varies substantially in the basic science literature, as well as clinical medicine. It is generally thought to result from neuroplastic changes in the peripheral and central nervous system (CNS) that lead to sensitization of pronociceptive pathways. While there are many proposed mechanisms for OIH, 5 mechanisms involving the central glutaminergic system, spinal dynorphins, descending facilitation, genetic mechanisms, and decreased reuptake and enhanced nociceptive response have been described as the important mechanisms. Of these, the central glutaminergic system is considered the most common possibility. Another is the hypothesis that N-methyl-D-aspartate (NMDA) receptors in OIH include activation, inhibition of the glutamate transporter system, facilitation of calcium regulated intracellular protein kinase C, and cross talk of neural mechanisms of pain and tolerance. Clinicians should suspect OIH when opioid treatment's effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the original pain, and increased levels of pain with increasing dosages. The treatment involves reducing the opioid dosage, tapering them off, or supplementation with NMDA receptor modulators. This comprehensive review addresses terminology and definition, prevalence, the evidence for mechanism and physiology with analysis of various factors leading to OIH, and effective strategies for preventing, reversing, or managing OIH.

A comprehensive review of opioid-induced hyperalgesia.

Pharmacological Management of Persistent Pain in Older Persons

Medications which bind to opioid receptors are increasingly being prescribed for the treatment of multiple and diverse chronic painful conditions. Their use for acute pain or terminal pain is well accepted. Their role in the long-term treatment of chronic noncancer pain is, however, controversial for many reasons. One of the primary reasons is the well-known phenomenon of psychological addiction that can occur with the use of these medications. Abuse and diversion of these medications is a growing problem as the availability of these medications increases and this public health issue confounds their clinical utility. Also, the extent of their efficacy in the treatment of pain when utilized on a chronic basis has not been definitively proven. Lastly, the role of opioids in the treatment of chronic pain is also influenced by the fact that these potent analgesics are associated with a significant number of side effects and complications. It is these phenomena that are the focus of this review. Common side effects of opioid administration include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and addiction are clinical concerns that may prevent proper prescribing and in turn inadequate pain management. Less common side effects may include delayed gastric emptying, hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. The most common side effects of opioid usage are constipation (which has a very high incidence) and nausea. These 2 side effects can be difficult to manage and frequently tolerance to them does not develop; this is especially true for constipation. They may be severe enough to require opioid discontinuation, and contribute to under-dosing and inadequate analgesia. Several clinical trials are underway to identify adjunct therapies that may mitigate these side effects. Switching opioids and/or routes of administration may also provide benefits for patients. Proper patient screening, education, and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events. Opioids can be considered broad spectrum analgesic agents, affecting a wide number of organ systems and influencing a large number of body functions.

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Opioid complications and side effects.

Background: Epidural injection of corticosteroids is one of the most commonly used interventions in managing chronic spinal pain However, there has been a lack of well-designed randomized, controlled studies to determine the effectiveness of epidural injections Consequently, debate continues as to the value of epidural steroid injections in managing spinal pain Objective: To evaluate the effect of various types of epidural steroid injections (interlaminar, transforaminal, and caudal), in managing various types of chronic spinal pain (axial and radicular) in the neck and low back regions Study Design: A systematic review utilizing the criteria established by the Agency for Healthcare Research and Quality (AHRQ) for evaluation of randomized and non-randomized trials, and criteria of Cochrane Musculoskeletal Review Group for randomized trials were used Methods: Data sources included relevant English literature performed by a librarian experienced in Evidence Based Medicine (EBM), as well as manual searches of bibliographies of known primary and review articles and abstracts from scientific meetings within the last 2 years Three reviewers independently assessed the trials for the quality of their methods Subgroup analyses were performed among trials with different control groups, with different techniques of epidural injections (interlaminar, transforaminal, and caudal), with different injection sites (cervical/thoracic, lumbar/sacral), and with timing of outcome measurement (short- and long-term) Outcome Measures: The primary outcome measure is pain relief Other outcome measures were functional improvement, improvement of psychological status, and return to work Short-term improvement is defined as 6 weeks or less, and long-term relief is defined as 6 weeks or longer Results: In managing lumbar radicular pain with interlaminar lumbar epidural steroid injections, the evidence is strong for short-term relief and limited for long-term relief In managing cervical radiculopathy with cervical interlaminar epidural steroid injections, the evidence is moderate The evidence for lumbar transforaminal epidural steroid injections in managing lumbar radicular pain is strong for short-term and moderate for long-term relief The evidence for cervical transforaminal epidural steroid injections in managing cervical nerve root pain is moderate The evidence is moderate in managing lumbar radicular pain in post lumbar laminectomy syndrome The evidence for caudal epidural steroid injections is strong for short-term relief and moderate for long-term relief, in managing chronic pain of lumbar radiculopathy and postlumbar laminectomy syndrome Conclusion: There is moderate evidence for interlaminar epidurals in the cervical spine and limited evidence in the lumbar spine for long-term relief The evidence for cervical and lumbar transforaminal epidural steroid injections is moderate for long-term improvement in managing nerve root pain The evidence for caudal epidural steroid injections is moderate for long-term relief in managing nerve root pain and chronic low back pain

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Epidural steroids in the management of chronic spinal pain: a systematic review.

BACKGROUND\nOpioid abuse has continued to increase at an alarming rate since our last opioid guidelines were published in 2005. Available evidence suggests a continued wide variance in the use of opioids, as documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration.\n\n\nOBJECTIVES\nThe objectives of opioid guidelines by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to bring consistency in opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion.\n\n\nDESIGN\nA broadly based policy committee of recognized experts in the field evaluated the available literature regarding opioid use in managing chronic non-cancer pain. This resulted in the formulation of the review and update of the guidelines published in 2006, a series of potential evidence linkages representing conclusions, followed by statements regarding the relationships between clinical interventions and outcomes.\n\n\nMETHODS\nThe elements of the guideline preparation process included literature searches, literature synthesis, consensus evaluation, open forum presentations, formal endorsement by the Board of Directors of the American Society of Interventional Pain Physicians, and peer review. Based on the criteria of the U.S. Preventive Services Task Force, the quality of evidence was designated as Level I, II, and III, with 3 subcategories in Level II, with Level I described as strong and Level III as indeterminate. The recommendations were provided from 1A to 2C, varying from strong recommendation with high quality evidence to weak recommendation with low-quality or very low-quality evidence.\n\n\nRESULTS\nAfter an extensive review and analysis of the literature, which included systematic reviews and all of the available literature, the evidence for the effectiveness of long-term opioids in reducing pain and improving functional status for 6 months or longer is variable. The evidence for transdermal fentanyl and sustained-release morphine is Level II-2, whereas for oxycodone the level of evidence is II-3, and the evidence for hydrocodone and methadone is Level III. There is also significant evidence of misuse and abuse of opioids. The recommendation is 2A - weak recommendation, high-quality evidence: with benefits closely balanced with risks and burdens; with evidence derived from RCTs without important limitations or overwhelming evidence from observational studies, with the implication that with a weak recommendation, best action may differ depending on circumstances or patients' or societal values.\n\n\nCONCLUSION\nOpioids are commonly prescribed for chronic non-cancer pain and may be effective for short-term pain relief. However, long-term effectiveness of 6 months or longer is variable with evidence ranging from moderate for transdermal fentanyl and sustained-release morphine with a Level II-2, to limited for oxycodone with a Level II-3, and indeterminate for hydrocodone and methadone with a Level III. These guidelines included the evaluation of the evidence for the use of opioids in the management of chronic non-cancer pain and the recommendations for that management. These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Because of the changing body of evidence, this document is not intended to be a \"standard of care.\

Opioids in the management of chronic non-cancer pain

Background Opioid abuse has continued to increase at an alarming rate since our last opioid guidelines were published in 2005. Available evidence suggests a continued wide variance in the use of opioids, as documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration. Objectives The objectives of opioid guidelines by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to bring consistency in opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion. Design A broadly based policy committee of recognized experts in the field evaluated the available literature regarding opioid use in managing chronic non-cancer pain. This resulted in the formulation of the review and update of the guidelines published in 2006, a series of potential evidence linkages representing conclusions, followed by statements regarding the relationships between clinical interventions and outcomes. Methods The elements of the guideline preparation process included literature searches, literature synthesis, consensus evaluation, open forum presentations, formal endorsement by the Board of Directors of the American Society of Interventional Pain Physicians, and peer review. Based on the criteria of the U.S. Preventive Services Task Force, the quality of evidence was designated as Level I, II, and III, with 3 subcategories in Level II, with Level I described as strong and Level III as indeterminate. The recommendations were provided from 1A to 2C, varying from strong recommendation with high quality evidence to weak recommendation with low-quality or very low-quality evidence. Results After an extensive review and analysis of the literature, which included systematic reviews and all of the available literature, the evidence for the effectiveness of long-term opioids in reducing pain and improving functional status for 6 months or longer is variable. The evidence for transdermal fentanyl and sustained-release morphine is Level II-2, whereas for oxycodone the level of evidence is II-3, and the evidence for hydrocodone and methadone is Level III. There is also significant evidence of misuse and abuse of opioids. The recommendation is 2A - weak recommendation, high-quality evidence: with benefits closely balanced with risks and burdens; with evidence derived from RCTs without important limitations or overwhelming evidence from observational studies, with the implication that with a weak recommendation, best action may differ depending on circumstances or patients' or societal values. Conclusion Opioids are commonly prescribed for chronic non-cancer pain and may be effective for short-term pain relief. However, long-term effectiveness of 6 months or longer is variable with evidence ranging from moderate for transdermal fentanyl and sustained-release morphine with a Level II-2, to limited for oxycodone with a Level II-3, and indeterminate for hydrocodone and methadone with a Level III. These guidelines included the evaluation of the evidence for the use of opioids in the management of chronic non-cancer pain and the recommendations for that management. These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Because of the changing body of evidence, this document is not intended to be a "standard of care."

/pdf/opioids-in-the-management-of-chronic-non-cancer-pain-an-2m7snzivvw.pdf

Rajive Adlaka

Papers

Opioid complications and side effects.

Epidural steroids in the management of chronic spinal pain: a systematic review.

Opioids in the management of chronic non-cancer pain

Opioids in the management of chronic non-cancer pain: an update of American Society of the Interventional Pain Physicians' (ASIPP) Guidelines.