Pharmacology/Drug Development

Fibromyalgia (FM) is a chronic pain syndrome associated with fatigue, insomnia, dyscognition, and emotional distress. Critical illness mechanisms include central sensitization to nociceptive and non-nociceptive stimuli often resulting in hypersensitivity to all sensory input.

The opioid epidemic in the U.S has gotten payers, prescribers, and policymakers alike interested in trends in opioid use. Despite no recognized opioid crisis in Europe, several countries have reported an increase in opioid-related deaths, which has further prompted discussion on the need of monitoring of opioid prescriptions. This study was conducted to offer information on opioid use during the escalation of the U.S. opioid epidemic in Finland, a Nordic country with universal tax-based health care. This is a nationwide retrospective register-based cohort study on all individuals in Finland who were dispensed opioids in 2009-2017 (n of unique patients = 1,761,584). By using the unique personal identification code assigned to every Finnish resident, we linked data from nationwide registers on dispensed drugs, medical history, and socio-demographic parameters. We report a wide set of patient demographics, dispensing trends for all opioid Anatomical Therapeutic Chemical (ATC) classes, and reasons for opioid initiation based on diagnostic coding for the most recent health care visit. For a cohort of incident opioid users with a four-year wash-out period (n = 1 370 057), we also present opioid use patterns in a three-year follow-up: the likelihood of becoming a persistent user or escalating from weak to strong opioids. A steady 7% of the Finnish population were dispensed opioids annually in 2009-2017. The mean annual quantity of dispensed opioids per opioid patient increased between 2009 and 2017 by 33%, reaching 2 583 oral morphine equivalent mg (OMEQ)/patient/year in 2017. The median quantity of dispensed opioids was lower: 315 OMEQ/year/patient. Depending on the opioid ATC class, there were either increasing or decreasing numbers of patients who had been dispensed said opioid class, and also in the mean quantity. The most common reason for opioid initiation was post-surgical pain (20%), followed by musculoskeletal pain (15%), injury (8.3%), and non-postsurgical dental pain (6.2%). 94% of new opioid initiators started with a weak opioid, i.e. codeine or tramadol. 85% of the patients who had been dispensed a weak opioid were not dispensed an opioid subsequently 3-6 months after the first one, and 95% of them had not escalated to a strong opioid in a 3-year follow-up. The number of patients dispensed opioids in Finland did not change during the escalation of the opioid epidemic in the U.S., but there were changes in the quantity of opioids dispensed per patient. Opioid therapy was typically initiated with weak opioid, the initial dispensed prescription was relatively small, and escalation to strong opioids was rare. A considerable share of patients had been prescribed opioids for chronic non-cancer pain – a type of pain where the risk-benefit ratio of opioids is controversial.

Existing guidelines advocate an updated therapeutic algorithm for chronic neuropathic pain (NeP), but pharmacotherapeutic management should be individualized to pain phenotypes to achieve higher efficacy. This study was aimed to evaluate the efficacy of medications, based on NeP phenotypes, and to propose symptom-based pharmacotherapy. This retrospective study was enrolled 265 outpatients with chronic NeP related to spinal disorders. The patients were classified into three groups: spinal cord-related pain, radicular pain, and cauda equina syndrome. Data were obtained from patient-based questionnaires using Neuropathic Pain Symptom Inventory (NPSI) and the Brief Scale for Psychiatric Problems in Orthopaedic Patients, and from clinical information. The proportions of patients with ≥ 30% and ≥ 50% reduction in NPSI score for each pain subtype (spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia) and drugs were evaluated. The pain reduction rate was significantly lower in patients with spinal cord-related pain, especially for paresthesia/dysesthesia. For spinal cord-related pain, duloxetine and neurotropin had insufficient analgesic effects, whereas mirogabalin was the most effective. Pregabalin or mirogabalin for radicular pain and duloxetine for cauda equina syndrome are recommended in cases of insufficient analgesic effects with neurotropin. The findings could contribute to better strategies for symptom-based pharmacotherapeutic management.

We estimate the probability of successful development and duration of clinical trials for medications to treat neuropathic and nociceptive pain. We also consider the effect of the perceived abuse potential of the medication on these variables.

Moderate-to-severe atopic dermatitis (AD) often requires long-term management with systemic therapies.

Baricitinib (Olumiant) is an oral small molecule inhibitor of Janus kinase (JAK)1 and JAK2, which have been implicated in the pathogenesis of atopic dermatitis (AD). In phase III studies in adults with moderate to severe AD who were inadequately controlled with topical corticosteroids (TCS) or systemic treatments (e.g. ciclosporin), or for whom these therapies were not advisable, baricitinib, alone or in combination with TCS, achieved significant and/or clinically relevant improvements in multiple measures of disease severity, pruritus, skin pain, sleep disturbance and health-related quality of life (HR-QOL) over 16 weeks. Benefit onset was rapid, with efficacy generally sustained over the longer term (treatment duration ≤ 68 weeks). In this patient population, the safety profile of baricitinib was consistent with that established in the moderate to severe rheumatoid arthritis (RA) population. Although further longer-term data would be beneficial, current evidence indicates that baricitinib, alone or in combination with TCS, provides an oral alternative to subcutaneous biologics for the treatment of moderate to severe AD in adults who are candidates for systemic therapy.

There is conflicting evidence on the association between intrapartum epidural analgesia and risk of autism spectrum disorder (ASD) in offspring.

The gut microbiome plays critical roles in human health and disease. Recent studies suggest it may also be associated with chronic pain and postoperative pain outcomes. In animal models, the composition of the gut microbiome changes after general anesthesia and affects the host response to medications, including anesthetics and opioids. In humans, the gut microbiome is associated with the development of postoperative pain and neurocognitive disorders. Additionally, the composition of the gut microbiome has been associated with pain conditions including visceral pain, nociplastic pain, complex regional pain syndrome, and headaches, partly through altered concentration of circulating bacterial-derived metabolites. Furthermore, animal studies demonstrate the critical role of the gut microbiome in neuropathic pain via immunomodulatory mechanisms. This article reviews basic concepts of the human gut microbiome and its interactions with the host and provide a comprehensive overview of the evidence linking the gut microbiome to anesthesiology, critical care, and pain medicine.