Discover the most talked about and latest scientific content & concepts.

Journal: Journal of pain & palliative care pharmacotherapy


ABSTRACT Rheumatoid arthritis (RA) is a painful, debilitating disease characterized by inflammation of the joints, with the proliferation of the synovium and the progressive erosion of cartilage and bone. The treatment of RA is still unsatisfactory, but a number of powerful disease-modifying antirheumatic drugs have become available, such as methotrexate (MTX). Even in the current era of biological targeted therapies, MTX remains the initial preferred antirheumatic drug and is considered to be the gold standard for treatment of RA. The combination of its perceived efficacy, acceptable safety profile, and low cost, as well as decades of clinical experience, makes MTX the cornerstone of treatment for RA and the anchor drug in combination with various biological agents. In this review, the authors aim to summarize the research done in the field of drug delivery systems of MTX according to its routes of administration for treatment of RA. The last part of the review addresses combination therapy with MTX and future direction in the drug delivery of MTX. This review also provides the reader with a general overview of RA and its therapeutic strategies with respect of MTX, which may bring uniformity in medical practice for effective management of RA.

Concepts: Pharmacology, Medicine, Rheumatoid arthritis, Therapy, Osteoarthritis, Drugs, Methotrexate, Disease-modifying antirheumatic drug


ABSTRACT Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a “main stream” pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. In a single-dose, open-label study, patients inhaled a single 15.1 ± 0.1 mg dose of cannabis using the Syqe Inhaler device. Blood samples for Δ(9)-tetrahydrocannabinol (THC) and 11-hydroxy-Δ(9)-THC were taken at baseline and up to 120 minutes. Pain intensity (0-10 VAS), adverse events, and satisfaction score were monitored following the inhalation. A uniform pharmacokinetic profile was exhibited across all participants (Δ(9)-THC plasma Cmax ± SD was 38 ± 10 ng/mL, Tmax ± SD was 3 ± 1 minutes, AUC0→infinity ± SD was 607 ± 200 ng·min/mL). Higher plasma Cmax increase per mg Δ(9)-THC administered (12.3 ng/mL/mg THC) and lower interindividual variability of Cmax (25.3%), compared with reported alternative modes of THC delivery, were measured. A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs.

Concepts: Pharmacology, Medicine, Distribution, Tetrahydrocannabinol, Pharmacokinetics, Cannabis, Neuropathic pain, Medical cannabis


Harmful and nonmedical use of prescription opioids has increased precipitously in the United States and some other countries in recent years, but not everywhere around the world. Addressing this problem requires attention to scientific data and to objective and balanced consideration of factors driving the problems. Unfortunately, the situation has been blurred by some politicians, health professionals, and the media by their using inadequate concepts, misrepresenting and exaggerating facts, and demonizing pain patients. In this article, we analyze what has occurred and present what we believe to be a balanced view of the problems. We advocate comprehensive drug control policies implemented in a way to reduce harmful use and diversion problems balancing the public health benefits and risks of opioid medications. We make recommendations for responsible prescribing, including implementing the World Health Organization (WHO) policy guidelines and similar United Nations Office of Drug Control (UNODC), which we believe can contribute measurably to the prevention of diversion of prescription opioids while ensuring patient access to the most appropriate medicines. Measures to reduce the risks of nonmedical use of opioid medicines should be based to the greatest extent possible on accurate evaluation of the mechanisms leading to such use, including diversion activities.

Concepts: Pharmacology, Public health, United States, Drug, Opioid, Pharmaceutical drug, Implementation, World Health Organization


ABSTRACT Management of postoperative pain remains an important clinical problem throughout the world. Using the PAIN-OUT acute pain registry database to examine perioperative pain management in orthopedic surgery patients, we compared patient-reported outcomes (PROs) in a pooled sample obtained from four American hospitals (N = 473) with PROs in a pooled sample of 20 European institutions (N = 8799). Most American hospitals consistently assess acute pain in surgical patients due to Joint Commission accreditation guidelines. Therefore, we hypothesized that this practice would create a climate of clinical staff sensitivity to patients' pain and a greater readiness to intervene when pain is higher than one would find in Europe as a whole. American institutions might then provide better control of postoperative pain after orthopedic surgery than European institutions. Because of the large sample sizes, our analyses focused on effect size rather than statistical significance. Evaluation of the pain PROs revealed that European patients reported much lower Worst Pain on the first day after orthopedic surgery than American patients. The mean Worst Pain (± SD) for Europeans was 5.4 (2.5) but for Americans the mean was 7.4 (2.7), p < .0001, a large effect size. Europeans also reported significantly less emotional discomfort, less interference of pain with activity and lower Least Pain. Nonetheless, 98.3% of American patients received opioids on the ward on the first postoperative day compared to 70.2% of European patients, and 41.1% received regional analgesia on the ward while 15.9% of European patients received regional analgesia (both small effect sizes). Overall, the results are clear in demonstrating much better pain control in the ensemble of European countries as compared to the United States.

Concepts: United States, Statistical significance, Opioid, Pain, Effect size, Suffering, Pain management, Statistical power


The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.


Topical analgesics are effective and alternative means to systemic therapy, often minimizing the adverse drug effects and complications of systemic analgesic use. Despite the number of available topical analgesics, there is little direction provided in practice guidelines on their appropriate use and little is known about patterns of their prescribing. To begin understanding these knowledge gaps, we sought provider perspectives on topical analgesic use at a large academic medical center. This electronic survey seeks to explore the perceptions and prescription patterns of topical analgesics among prescribers in a large academic medical center, where the availability of topical analgesics varies. Among topical analgesics, lidocaine (78%) is prescribed more frequently than nonsteroidal anti-inflammatory drugs (NSAIDs; 41%) or morphine (3%). Formulations and indications of use varied between faculty physicians and nonfaculty providers. Reasons for prescribing were largely based on anecdotal experience. Based on the survey results, it is clear that more topical agents are needed to manage pain; however, so too is guidance on appropriate prescribing.


Peripheral nerve hyperexcitability (PNH) syndromes are a rare set of neuromuscular disorders that include cramp-fasciculation syndrome (CFS) and Isaacs syndrome (IS). Successful treatment of these diseases has been achieved with antiepileptic medications; however, chronic pain symptoms can persist. We provide a case report of a 25-year-old female who has suffered from painful severe muscle spasms and fasciculations since childhood. With CFS as our working diagnosis, a treatment regimen using interventional pain techniques, including sympathetic chain blocks, ketamine infusions, and trigger point injections, resulted in a significant decrease in the patient’s chronic pain symptoms. This case offers a novel application of interventional pain procedures and may help further our understanding of PNH syndromes.


Acute pain is a prevalent issue for patients recovering from surgical procedures. Methadone has been recognized as a unique option for treatment of surgical pain due to its multiple mechanisms of analgesia and its potential to decrease tolerance to other opioids. Studies of methadone use in postoperative settings are sparse in part due to safety concerns, such as complex pharmacokinetics, risk of respiratory depression, and association with arrhythmias. In this case study of a 70-year-old male with postsurgical abdominal pain, methadone utilization over a period of 9 days resulted in patient-reported analgesia and aided in de-escalating overall opioid use. More studies are needed to develop guidance on how methadone can be used to relieve pain following surgical procedures.


Opioids are first-line therapy for cancer-related pain. In addition, corticosteroids are commonly utilized as adjuvant analgesics for pain and other symptoms in the oncology setting with limited supporting data. A retrospective analysis was conducted evaluating adult hospitalized patients receiving opioids who received once-daily dexamethasone on the recommendation of a specialty palliative care team during their hospitalization from January 1, 2015, to January 1, 2016. Primary end point was to describe prescribing patterns of dexamethasone in this patient population and secondarily examining any effect on oral morphine equivalent daily dose (MEDD), numeric pain score (NPS), and unwanted effects at 24 and 48 hours after the first dose of dexamethasone. Fifty-nine patients received an average dose of 13 mg (SD = 10) of dexamethasone for cancer-related pain, primarily acute pain (n = 36, 61%). Many died before hospital discharge or soon thereafter (n = 28, 47.5%). Although not statistically significant, our study shows a decrease of 23% and 19% in MEDD and NPS, respectively, without change in WBC after dexamethasone. A specialty palliative care team most often used once-daily dexamethasone for cancer-related pain in patients near the end of life. There were trends toward lower MEDD and NPS, but more robust studies are needed for validation.


Ketamine, lidocaine, and mexiletine are potential nonopioid adjuvant medications for the use of refractory cancer-related pain, particularly when opioids are demonstrating limited objective benefit. This is a case report of a single patient admitted to a large academic medical center in the United States. The patient is a 43-year-old woman with a history of Crohn’s disease complicated by rectal squamous cell carcinoma and complex, progressive, and intractable pelvic and rectal pain. Over the course of hospitalization, her pain demonstrated limited opioid responsiveness despite marked fluctuations of her oral morphine equivalent doses. She also demonstrates variable responsiveness to ketamine. Lidocaine continuous infusion ultimately proves beneficial, and she is discharged after conversion to oral mexiletine. An overview of the hospital system’s protocols for ketamine and lidocaine continuous infusions for pain and considerations for transitioning to mexiletine from lidocaine infusion are included.