The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier.

As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear.

Cluster Headache: Opportunities for Pharmacists to Improve Care.

Cluster headache (CH) is a primary headache (PH) disorder characterized by recurrent attacks of severe/extremely severe unilateral pain and associated symptoms. While less prevalent than other PHs such as migraine, CH impact is substantial given the agonizing pain, negative effect on daily productivity, impaired mental health, and increased costs. Cluster headache is not optimally treated and few clinical trials are available to model therapy, especially dosing and administration.

Safety of tapentadol compared with other opioids in chronic pain treatment: network meta-analysis of randomized controlled and withdrawal trials.

Objective: To assess the relative safety of oral tapentadol PR and other opioid analgesics for moderate or severe chronic pain in adults, we conducted a systematic review and network meta-analysis (NMA).

Methods: A systematic review was conducted to identify randomized controlled trials (RCTs) and randomized withdrawal trials of tapentadol with other WHO stage II and III opioid analgesics in patients with moderate or severe chronic pain. Searches were conducted in MEDLINE, EMBASE, PubMed, Cochrane databases and trial registries.

Clinical and biobehavioral perspectives: Is medication overuse headache a behavior of dependence?

Medication overuse headache (MOH), previously known as analgesic abuse headache or medication misuse headaches, is a common form of chronic headache disorder that has a detrimental impact on health and society. Although it has been widely accepted that overusing abortive medications is paradoxically the cause of MOH and drug discontinuation is the treatment of choice, ongoing debates exist as to whether drug consumption per se is the cause or consequence of headache chronification. Certain features in MOH such as their compulsive drug-seeking behavior, withdrawal headaches and high relapse rates share similarities with drug dependence, suggesting that there might be common underlying biological and psychobehavioral mechanisms.

Impact of coronavirus disease 2019 (COVID-19) pandemic on patients with migraine: a web-based survey study.

Background: Since the declaration COVID-19 as a pandemic, healthcare systems around the world have faced a huge challenge in managing patients with chronic diseases. Patients with migraine were specifically vulnerable to inadequate medical care. We aimed to investigate the "real-world" impact of COVID-19 pandemic on migraine patients, and to identify risk factors for poor outcome.

Pain Chemogenomics Knowledgebase (Pain-CKB) for Systems Pharmacology Target Mapping and Physiologically Based Pharmacokinetic Modeling Investigation of Opioid Drug-Drug Interactions.

More than 50 million adults in America suffer from chronic pain. Opioids are commonly prescribed for their effectiveness in relieving many types of pain. However, excessive prescribing of opioids can lead to abuse, addiction, and death.

Pain, Motivation, Migraine, and the Microbiome: New Frontiers for Opioid Systems and Disease.

For decades the broad role of opioids in addiction, neuropsychiatric disorders, and pain states has been somewhat well established. However, in recent years, with the rise of technological advances, not only is the existing dogma being challenged, but we are identifying new disease areas in which opioids play a critical role. This review highlights four new areas of exploration in the opioid field.

The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study.

Background: We evaluated the efficacy of fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, in patients with chronic migraine (CM) with and without medication overuse (MO).

Methods: In a 12-week, phase 3 trial, patients with CM were randomized to fremanezumab quarterly (675 mg/placebo/placebo), monthly (675 mg/225 mg/225 mg), or placebo. Post hoc analyses assessed the impact of fremanezumab in patients with and without MO (monthly use of acute headache medication ≥15 days, migraine-specific acute medication ≥10 days, or combination medication ≥10 days) on efficacy outcomes, including headache days of at least moderate severity (HDs), and six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life (MSQoL) questionnaire scores.

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review.

Introduction: Interest is growing in the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific PAC1 receptor in migraine and in their antagonism as a strategy for migraine prevention.

Areas Covered: We discuss and critically evaluate (i) the evidence of the role of PACAP in migraine pathophysiology and (ii) the first clinical trials in migraine prophylaxis with monoclonal antibodies AMG 301 and ALD1910 which act against PAC1 and PACAP38 respectively. We examined PubMed, Scopus, and ClinicalTrials.

Review of lisdexamfetamine dimesylate in children and adolescents with attention deficit/hyperactivity disorder.

Objective: Lisdexamfetamine dimesylate is a stimulant prodrug with low abuse and diversion potential that is used in treatment of attention deficit hyperactivity disorder (ADHD) in children, adolescents and adults. This current literature review article aims to examine safety and efficacy of LDX in children and adolescents for the treatment of ADHD based on currently available data.

Methods: Relevant English language articles were identified through computerized searches of the MEDLINE database (PubMed and EMBASE) and clinical trials registry up to January 2020 using the following search terms: lisdexamfetamine dimesylate, pro-drug stimulant, attention-deficit and hyperactivity disorders, ADHD, safety, efficacy, children, adolescents, Vyvanse.

Low-Dose Naltrexone for Chronic Pain: Update and Systemic Review.

Purpose Of Review: The purpose of this review is to evaluate and explain our current understanding of the clinical use of low-dose naltrexone in the treatment of chronic pain.

Recent Findings: Recent pre-clinical uses and clinical studies further elucidate the use of low-dose naltrexone in the treatment of chronic pain. Low-dose naltrexone (LDN) has shown promise to reduce symptoms related to chronic pain conditions such as fibromyalgia, inflammatory bowel conditions, and multiple sclerosis.

Secondary headache attributed to exposure to or overuse of a substance.

Background: Secondary headaches attributed to exposure to or the overuse of a substance are classified under chapter eight in the International Classification of Headache Disorders 3rd edition. Three distinct sub-chapters consider: 1. Headache attributed to exposure to a substance, 2.

Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study.

Background: Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30).

No efficacy of transcranial direct current stimulation on chronic migraine with medication overuse: A double blind, randomised clinical trial.

Background: Transcranial direct current stimulation was suggested to provide beneficial effects in chronic migraine, a condition often associated with medication overuse for which no long-term therapy is available.

Methods: We conducted a randomised controlled trial to assess long-term efficacy of transcranial direct current stimulation. Adults diagnosed with chronic migraine and medication overuse were assigned to receive in a 1:1:1 ratio anodal, cathodal, or sham transcranial direct current stimulation daily for five consecutive days, along with standardised drug withdrawal protocol.

Considerations and Implications of Cannabidiol Use During Pregnancy.

Purpose Of Review: Cannabis is a naturally occurring plant that is composed of over sixty phytocannabinoids, of which cannabidiol (CBD) has been recently identified as having therapeutic potential.

Recent Findings: Although not clearly understood in its mechanism of action, CBD contains potent anti-inflammatory, anti-hyperalgesia, and analgesic qualities now being further analyzed for its use in the treatment of a plethora of diseases. Related to its large safety profile and lack of psychoactive effects typically associated with cannabis and tetrahydrocannabinol (THC), CBD is being used more frequently for self-treatment of chronic pain, anxiety, and depression.

A prospective real-world analysis of erenumab in refractory chronic migraine.

Background: Clinical trials have shown the safety and clinical superiority of erenumab compared to placebo in chronic migraine (CM). The aim of this analysis is to evaluate the effectiveness and tolerability of erenumab in a real-world setting in patients with refractory CM.

Methods: This is a prospective single centre real-world audit conducted in patients with CM with and without medication overuse, refractory to established preventive medications, who received monthly erenumab for 6 months.

Heroin-induced headache in female heroin addicts.

Objective: To investigate the manifestations and incidence of headaches caused by heroin in Chinese women.

Methods: This was a survey study conducted from 29 June to 3 July 2015 with women attending the Shanxi Drug Rehabilitation Centre for Women (China). All study subjects were newly admitted and had not begun their drug rehabilitation.

Interprofessional Collaboration in the Assessment and Management of Substance Use Risk.

Substance use disorder assessment strategies are increasingly being employed by dentistry, while adequate evaluation requires reaching out to other cotreating providers and collaborating on patient care. The field of dentistry has a range of barriers often not experienced in other professions, including limitations on e-record communication and clinical practice setting often isolated from the patient's general medical care. Barriers can be overcome if the dentist facilitates communication.

European Academy of Neurology guideline on the management of medication-overuse headache.

Background: The frequent use of medication to treat migraine attacks can lead to an increase in migraine frequency and is called medication-overuse headache (MOH).

Methods: Based on the available literature in this guideline, the first step in patient management is education and counselling.

Results: Patients with MOH should be managed by a multidisciplinary team of neurologists or pain specialists and behavioral psychologists.

Identification of candidate proteomic markers in the serum of medication overuse headache patients: An exploratory study.

Purpose Of The Study: The pathophysiological mechanism of medication overuse headache is uncertain; no distinctive markers have been described right now. The aim of this study was to conduct proteomic analyses on serum samples from patients with medication overuse headache and healthy individuals. Specifically, mono- (SDS-PAGE) and two-dimensional gel electrophoresis (2-DE) followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to evaluate changes in serum proteins.

Sustained response to onabotulinumtoxin A in patients with chronic migraine: real-life data.

Background: Treatment with onabotulinumtoxin A (BT-A) is safe and effective for chronic migraine (CM). Several studies assessed possible predictors of response to treatment with BT-A, but there is little knowledge on the frequency and predictors of sustained response. The aim of this study was to evaluate sustained response to BT-A in patients with CM.