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Pain management epitomizes the value of a multidisciplinary approach to caring for patients, yet regrettably, the term pain management has too often become synonymous with prescribing opioids only. Optimal chronic pain management requires a skillset most conducive to a multidisciplinary team approach and should be performed in a scientifically and clinically sound manner. It is with these facts in mind that we offer our view of the Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain.

The ongoing media maelstrom regarding opioids and classification of an "opioid crisis" during the initial decade of this millennium has stirred awareness, outrage and action among regulatory and other government agencies, professional clinician organizations, community pharmacy policies, legislators, patient advocacy groups, anti-opioid advocate groups, and others. However, mass media reports often skew or misdirect the aggregate facts in a possible effort to abridge or sensationalize stories. 1 Discernable distinctions, for example, are rarely drawn between licit pharmaceutical fentanyl, illicit fentanyl analogues, and certain highly potent analogues approved only for ungulates. The omission of this information has resulted in distorted public information that has far reaching consequences in medicine and policy development, as it leads to misunderstanding and misinterpretation of the facts by politicians, lay people and many clinicians. 2 It is particularly relevant today, as pharmaceutical fentanyl is often an essential drug for intubation regularly required for ventilation procedures in declining patients that may succumb to novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These distinctions are critical in the shifting landscape of the opioid crisis as prescriptions for opioids decrease yet overdose deaths remain alarmingly prevalent and continue to rise.Licit fentanyl was first synthesized in the 1950s via manipulation of another phenylpiperidine, meperidine, in an effort to develop a novel analgesic agent and laying the groundwork for pharmaceutical fentanyl and multiple analogues. Only a small percentage of those analogues are actually approved for medical use. 2 The remainder are dangerously potent with high binding affinity to opioid receptors and rapid entry to the CNS. These characteristics make them particularly hazardous when added to other illicit substances such as heroin, unbeknownst to the end-user with potentially deadly consequences. 3 Illicit fentanyl has had a dramatically increasing impact on opioid overdose deaths in the US over the past decade. According to provisional data from the 2018 Centers for Disease Control and Prevention, over half of the opioid-related overdose deaths in 2018 involved non-methadone synthetic opioids; the most common of which was illicitly manufactured fentanyl. 4 Perhaps more telling are the annual data released by the New Hampshire Department of Justice, with the most recent of which indicating that less than 7% of 2019 opioid overdose deaths in the state were due to prescription opioids. 5 These illicit opioids have affected the landscape of opioid abuse to the extent that the Drug Enforcement Agency (DEA) chose to emergently schedule all fentanyl-related substances (FRS) to schedule I as of February 2018.

This study compares the pharmacokinetic (PK) profile, adhesion, and safety of lidocaine topical system 1.8%, a novel lidocaine topical system approved to treat postherpetic neuralgia, under conditions of heat and exercise vs normal conditions. Materials and Methods: This open-label, 3-period, 3-treatment crossover study randomized 12 healthy adults to receive three lidocaine topical systems 1.8% during each of three treatment periods, with 7-day washouts between treatments. The product was applied to the mid-lower back and was removed after 12 hours. During Treatment A, subjects exercised on a bicycle for 30 minutes at 0, 2.5, 5.5, and 8.5 hours. During Treatment B, heat (temperature set at 36.7-40.3°C) was applied at 0 and 8.5 hours. Treatment C was normal conditions. The PK profile of each subject under exercise and heat conditions was compared to normal conditions. Skin irritation, adhesion, and adverse events were assessed. Results: Twelve subjects completed the study. Exposure to external heat resulted in increased peak plasma concentration of lidocaine with a mean C max of 160.3±100.1 ng/mL vs 97.6±36.9 ng/mL under normal conditions, with no effect on the extent of exposure (AUC). Concentrations returned to normal within 4 hours after the heat was removed. No clinically relevant differences in absorption were observed under exercise conditions with a mean C max of 90.5±25.4 ng/mL and no effect on the extent (AUC) of lidocaine exposure was observed relative to normal conditions. No systems detached during the study. Adverse events were mild, with none leading to discontinuation. Conclusion: Transient heat exposure resulted in increased lidocaine plasma concentrations compared to normal conditions, whereas exercise had no effect. The effects of heat appear to be immediate, reversible, and below systemic therapeutic threshold in antiarrhythmic treatment (1000-1500 ng/mL), and well below the safe systemic threshold of 5000 ng/mL. Lidocaine topical system 1.8% remained adhered to the skin and was well tolerated under all conditions. ClinicalTrials.gov: NCT04150536.

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The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain. The use of leucovorin in this patient decreased pain scores, which were clinically significant and increased functionality. This case demonstrates the importance of pharmacogenetics testing in patients, as this can help direct providers to better therapeutic options for their patients.

As a means of mitigating the now concluded prescription opioid crisis in the United States, the Drug Enforcement Administration (DEA) has, in its infinite wisdom, embarked on a campaign of annually reducing the Aggregate Production Quota (APQ) of opioids each year since 2017. According to the DEA, they began reducing the APQ because there was no longer the need for a 25% "buffer" of excess opioids due to decreases in prescribing each year. 1 In 2017, production of almost every opioid manufactured in the United States was reduced by at least 25%. 1 In 2018, APQs of opioids-including oxycodone, hydrocodone, oxymorphone, hydromorphone, morphine, codeine, meperidine, and fentanyl-were reduced by 20% compared to 2017 production. 2 For 2019, DEA reduced APQs only of "more commonly prescribed schedule II opioids, including oxycodone, hydrocodone, oxymorphone, hydromorphone, morphine, and fentanyl". 3 The 2020 production decreases affected 5 commonly-used opioids: Oxycodone production was decreased by 9%, hydrocodone by 19%, hydromorphone by 25%, fentanyl by 31%, and oxymorphone by 55%. 4 Given, in response to the need for increased availability of opioids associated with the COVID-19 crisis, DEA made small adjustments (increases of 10-15%) in production APQs in April of 2020 of analgesics including codeine, fentanyl, hydromorphone, and morphine. 5 Unfortunately, this action was too little, too late. Hospitals that had already been sounding the alarm for the past several years regarding routine shortages of parenteral opioids suddenly were faced with inadequate supplies essential for treating patients on ventilators amidst COVID-19, with the need for IV formulations increasing more than twofold. 6 By 2020, DEA reported that total domestic opioid production had decreased by 53% since 2016. 4 Irrespective, DEA recently released its proposed production decreases for 2021, which include an additional 20% reduction of fentanyl, a 15% reduction of oxycodone, a 12% decrease of hydrocodone, and a 9% reduction of hydromorphone, all compared to the original figures for 2020. Curiously, the proposed APQ of oxymorphone actually increased by 13% compared to the original APQ for 2020, keeping its level of production unchanged from the April, 2020 adjustment. 7 This most recent proposed APQ is bewildering, given that half a year ago, DEA felt compelled to adjust its APQs in response to a pandemic which is hardly over, with no certainty regarding the course that it will take. While April's manufacturing increase may have provided a temporary fix, concern has been raised