Although a detailed description of pain pathways and relevant medical interventions is beyond the scope of this paper, it suffices to say that much of our understanding of pain pathophysiology is recent, and that the field remains in infancy but rapidly evolving. Before 1800, clinicians regarded pain as an existential phenomenon, a consequence of aging . There was no regulation on the use of cocaine and opioids, resulting in widespread marketing and prescribing for many ailments ranging from diarrhea to toothache . The Harrison Narcotic Control Act of 1914, passed in response to the sudden emergence of street heroin abuse as well as iatrogenic morphine dependence, influenced both physician and patient alike to avoid opiates . Patients with unexplained pain in the 1920s were regarded as deluded, malingering, or abusers, and cancer patients through the 1950s were encouraged to wean themselves off opioids until their lives “could be measured in weeks” .
This attitude persisted into the latter half of the twentieth century; a general world-wide “opiophobia” is thoroughly detailed in contemporary literature. Morgan in 1985 and Zenz and Willweber-Strumpf in 1992 both describe a state of under-reliance of opioid analgesics and a resultant under-treatment of pain in Europe and North America [10, 11]. Several developments over this era served to increase awareness of pain under-treatment. A 1973 manuscript from Marks and Sachar in the Annals of Internal Medicine described a failure to treat patients in severe pain with adequate doses of opioid analgesics . Two decades later, Max  decried the same failure, invoking the conventional wisdom of the day that “therapeutic use of opiate analgesics rarely results in addiction.” This widespread belief was based upon two small retrospective publications from the 1980s: the first, published as a one paragraph letter to the editor without detailing any scientific rigor, described low (0.03%) addiction rates for inpatients receiving opioids for acute pain; the second, a retrospective review of 38 patients, demonstrated that only 2 of 38 patients with chronic pain developed misuse or abuse issues when receiving opioids [14, 15]. The scientific background for the use of opioids for non-malignant pain was therefore not based upon any demonstrable outcomes or safety studies.
The World Health Organization addressed the under-treatment of postoperative and cancer pain in 1986 with their Cancer Pain Monograph . A rapid improvement in the treatment of cancer pain soon unfurled in many countries, though not entirely, as many countries even today suffer from poor access to opioids . This further prompted a number of publications in the 1990s that questioned the state of pain under-treatment. Notably, Ronald Melzack in 1990  published an article in Scientific American that questioned why opioids were reserved solely for cancer pain and avoided entirely in chronic pain states. The newfound interest bore misconceptions, drawn largely by cancer pain specialists lacking expertise on other chronic, non-cancer pain, that equated the etiologies of malignant and non-malignant pain . This dangerous conflation disregards the complex biopsychosocial phenomena that is chronic pain, and despite many cautions to this effect, opioids grew into the primary modality of chronic non-cancer pain treatment in the USA .
Alongside this opioid evolution, the American Pain Society launched their influential “pain as the fifth vital sign” campaign in 1995, with intent to encourage proper, standardized evaluation and treatment of pain symptoms . The Veteran’s Health Administration lent support to the campaign with their 1999 adoption of pain as the fifth vital sign initiative .
Solidifying the national response to the aforementioned efforts, the Joint Commission (TJC) published standards for pain management in 2000, emphasizing the need for organizations to conduct quantitative assessments of pain as recommended by the Institute of Medicine . The Federation of State Medical Boards and the Drug Enforcement Agency also issued statements promising less regulatory scrutiny over opioid prescribers, thereby assuaging physician reluctance to prescribe more liberal amounts of opioid analgesics .
The rapid institution of strict standards for pain management in hospital systems culminated in several unintended consequences. Physicians were now mandated to provide adequate pain control by the TJC, resulting in a heavy reliance on opioid medications. The fear among hospital administration was that if new TJC benchmarks were not met, then they were unlikely to receive federal healthcare funds. Indeed, hospitals that invested more readily in opioid therapy generally received better satisfaction rates among their patient population . Pharmaceutical companies heavily pushed the use of opioids as a humane treatment option, often using paid physician consultants to expound on the safety and benefits of opioids use. Not prescribing opioids for a patient with pain risked being labeled as inhumane, often even to the extent of litigation for the under-treatment of pain . Trainees in pain medicine as well as other medical specialties were taught to rely more on opioids for pain treatment. Concurrently, pharmaceutical companies introduced new formulations, such as extended release oxycodone (OxyContin), which were frequently prescribed because of a presumed lower likelihood of abuse, while in reality were heavily abused. From 1997 to 2002, OxyContin prescriptions increased from 670,000 to 6.2 million . Overall opioid consumption continued to climb throughout the 2000s in the USA, rising from 46,946 kg consumed in the year 2000 to a peak of 165,525 kg in 2012 .
The initial response was favorable, and the push for better pain control appeared successful. One study found that the mean consumption of opiates per patient in the postanesthesia care unit (PACU) increased from 40.4 mg of morphine equivalent to 46.6 mg from 2000 to 2002 with no associated increase in length of stay, naloxone use, or nausea and vomiting . However, concerns soon began to surface regarding overzealous opioid treatment. One report found that the incidence of opioid oversedation more than doubled from 11.0 to 24.5 per 100,000 inpatient hospital days with the implementation of a new standardized, numerical pain treatment algorithm . The Institute for Safe Medication Practices began to establish a link between overaggressive pain management and substantial increases in the incidence of oversedation and associated fatal respiratory depression. The culture change, driven by intent to ensure access to pain relief, had opened the floodgates to the current opioid climate. In just the past 15 years, there has been a proportionate quadrupling of prescription opioid sales and mortality in both men and women based on National Vital Statistics System mortality statistics from the Centers for Disease Control and Prevention . Perplexingly, in addition to the increasing mortality, no study to this date has established level I evidence for the long-term safety and efficacy of opioid therapy in reducing chronic pain intensity and improving function. Instead, numerous other ills arising from opioid medication, such as hyperalgesia, increasing disability, and a host of other formidable problems, including endocrine and psychological co-morbidities, have emerged in relation to chronic opioid use.
It must be noted that pharmaceutical companies contributed significantly to the rise of the opioid epidemic, receiving considerable reprimands as a consequence. In 2007, as the opioid epidemic began to inflict profound damage, Purdue Pharma pleaded guilty to federal charges related to the misbranding of OxyContin. Purdue agreed to pay a total of $634.5 million to resolve Justice Department investigations, as well as a $19.5 million settlement to 26 states and the District of Columbia . Allegations accuse Purdue of intentionally downplaying the risk of addiction posed by OxyContin and misleading both physicians and the healthcare industry as a whole by overstating the benefits of opioids for chronic pain. At the time of this publication, at least 14 states have submitted lawsuits against the privately held Purdue, and the company has announced that it will cut its sales force in half and stop promoting opioids to physicians in a stark reversal of policy from recent decades.