Accepted

Migraine results in an enormous burden on individuals and societies due to its high prevalence, significant disability, and considerable economic costs. Current treatment options for migraine remain inadequate, and the development of novel therapies is severely hindered by the incomplete understanding of the mechanisms responsible for the pain. The sensory innervation of the cranial meninges is now considered a key player in migraine headache genesis. Recent studies have significantly advanced our understanding of some of the processes that drive meningeal nociceptive neurons, which may be targeted therapeutically to abort or prevent migraine pain. In this review we will summarize our current understanding of the mechanisms that contribute to the genesis of the headache in one migraine subtype – migraine with aura. We will focus on animal studies that address the notion that cortical spreading depression is a critical process that drives meningeal nociception in migraine with aura, and discuss recent insights into some of the proposed underlying mechanisms.

Sleep disturbance (SD) is common in atopic dermatitis (AD). We examined the longitudinal course of SD and relationship with itch in AD patients. A prospective, dermatology practice-based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits. At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 follow-ups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment scores over time included baseline PROMIS sleep-related impairment scores (0.74 [0.68-0.80]), having 3 to 6 nights of itch (2.22 [0.85-3.59]), and severe/very severe AD (4.40 [2.60-6.20]). A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course.

Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we performed a systematic study asking about the prevalence of familial trigeminal neuralgia, and which genes that have been identified in human TN studies and in animal models of trigeminal pain. MedLine, Embase, Cochrane Library and Web of Science were searched from inception to January 2021. 71 studies were included in the systematic review. Currently, few studies provide information about the prevalence of familial TN; the available evidence indicates that about 1-2% of TN cases have the familial form. The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A, CACNA1H, CACNA1F, KCNK1, TRAK1, SCN9A, SCN8A, SCN3A, SCN10A, SCN5A, NTRK1, GABRG1, MPZ gene, MAOA gene and SLC6A4. Their role in familial TN still needs to be addressed. The experimental animal studies suggest an emerging role of genetics in trigeminal pain, though the animal models may be more relevant for trigeminal neuropathic pain than TN per se. In summary, this systematic review suggests a more important role of genetic factors in TN pathogenesis than previously assumed.

Although coronavirus disease 2019 (COVID-19) most commonly manifests with acute respiratory symptoms, one very common symptom of COVID-19 is pain. As COVID-19 often causes peripheral or central neurological complications, it is anticipated that a number of the chronic pain complications of COVID-19 will be neuropathic. This review first examines the most common viral infections responsible for neurological complications including neuropathic pain. These encompass herpes zoster, HIV, poliovirus, enteroviruses, and several tropical viruses. Neurological complications of COVID-19 including in particular Guillain-Barré syndrome, myelitis, and stroke are reviewed with regards to their potential risk of chronic neuropathic pain. Prospective longitudinal cohorts of patients should be implemented to evaluate the exact risk of neuropathic pain after COVID-19.