Pain
-
Genetic variation in melanocortin-1 receptor (MC1R) has a known role in red hair. Studies on responses to noxious stimuli in red-haired individuals have also been conducted, with mixed findings. To investigate a possible divergence between variants responsible for red hair and pain sensitivity, we performed a genewide association analysis in the Orofacial Pain: Prospective Evaluation and Risk Assessment cohort. ⋯ The 5'-UTR variant rs3212361 was further identified as an expression quantitative trait locus, associated with reduced transcript levels of MC1R in the brain and in the peripheral tibial nerve. Hair colour association analysis of the loss-of-function 5'-UTR rs3212361 allele identified association with red hair, and red hair colour itself was associated with a reduced count of persistent pain conditions. Together, our results suggest that primarily different mechanisms-affecting expression levels vs protein activity-mediated by different genetic variants in the MC1R locus contribute to red hair and pain.
-
Nonsteroidal anti-inflammatory drugs, commonly known as COX-1/COX-2 inhibitors, can be effective in treating mild to moderate migraine headache. However, neither the mechanism by which these drugs act in migraine is known, nor is the specific contribution of COX-1 vs COX-2. ⋯ Compared to vehicle (control group), celecoxib reduced CSD-induced dilatation of dural arteries and activation of dural and pial macrophages significantly, but not dilatation or constriction of pial arteries and veins, or the occurrence of plasma protein extravasation. Collectively, these findings suggest that a mechanism by which celecoxib-mediated COX-2 inhibition might ease the intensity of migraine headache and potentially terminate an attack is by attenuating dural macrophages' activation and arterial dilatation outside the blood-brain barrier, and pial macrophages' activation inside the blood-brain barrier.
-
Most centrally acting migraine preventive drugs suppress frequency and velocity of cortical spreading depression (CSD). The purpose of the current study was to determine how the new class of peripherally acting migraine preventive drug (ie, the anti-CGRP-mAbs) affect CSD-an established animal model of migraine aura, which affects about 1/3 of people with migraine-when allowed to cross the blood-brain barrier (BBB). ⋯ Similarly, we cannot conclude that CGRP is involved in the propagation velocity or the neuronal silencing period (also called cortical recovery period) that follows the CSD because similar effects were observed when the isotype was used. These finding call for caution with interpretations of studies that claim to show direct central nervous system effects of CGRP-mAbs.
-
Conventional magnetic resonance imaging of patients with trigeminal neuralgia (TN) does not typically reveal associated brain lesions. Here, we identify a unique group of TN patients who present with a single brainstem lesion, who do not fulfill diagnostic criteria for multiple sclerosis (MS). We aim to define this new clinical syndrome, which we term TN associated with solitary pontine lesion (SPL-TN), using a clinical and neuroimaging approach. ⋯ The lesions demonstrated abnormal white-matter microstructure, characterized by lower fractional anisotropy, and higher mean, radial, and axial diffusivities compared with the unaffected side. The brainstem trigeminal fiber microstructure within a lesion highlighted the difference between SPL-TN lesions and MS plaques. In conclusion, SPL-TN patients have identical clinical features to TN but have a single pontine lesion not in keeping with MS and are refractory to surgical management.
-
Painful distal symmetrical polyneuropathy is common in HIV and is associated with reduced quality of life. Research has not explored the experience of neuropathic pain in people with HIV from a person-centred perspective. Therefore, a qualitative interview study was conducted to more deeply understand the experience and impact of neuropathic pain in this population. ⋯ Theme 3 reflects the struggle for pain relief, including participants' attempts to "exhaust all options" and limited success in finding lasting relief. The final theme describes how pain management is complicated by living with HIV; this theme includes the influence of HIV stigma on pain communication and pain as an unwanted reminder of HIV. These data support the relevance of investigating and targeting psychosocial factors to manage neuropathic pain in HIV.