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Sensory neuron nicotinic acetylcholine receptors (nAChRs) contribute to pain associated with tissue injury. However, there are marked differences between rats and mice with respect to both the properties and distribution of nAChR currents in sensory neurons. Since both species are used to understand pain signaling in humans, we sought to determine whether the currents present in either species was reflective of those present in human sensory neurons. Neurons from lumbar 4/5 dorsal root ganglia were obtained from adult male and female organ donors. Nicotine-evoked currents were detected in 40 of 47 neurons (85%). In contrast to the naïve mouse, in which almost all nAChR currents are transient, or the rat, in which both mouse-like transient and more slowly activating and inactivating currents are detected, all the currents in human DRG neurons were slow, but slower than those in the rat. Currents were blocked by the nAChR antagonists mecamylamine (30 µM), but not by the TRPA1 selective antagonist HC-030031 (10µM). Single cell PCR analysis of nicotinic receptor subunit expression in human DRG neurons are consistent with functional data indicating that receptor expression is detected 85 ± 2.1% of neurons assessed (n = 48, from 4 donors). The most prevalent co-expression pattern was α3/β2 (95 ± 4% of neurons with subunits), but α7 subunits were detected in 70 ± 3.4% of neurons. These results suggest that there are not only species differences in the sensory neuron distribution of nAChR currents between rodent and human, but that the subunit composition of the channel underlying human nAChR currents may be different from those in the mouse or rat. PERSPECTIVE: The properties and distribution of nicotine-evoked currents in human sensory neurons were markedly different from those previously observed in mice and rats. These observations add additional support to the suggestion human sensory neurons maybe an essential screening tool for those considering moving novel therapeutics targeting primary afferents into clinical trials.
Learn More >Cluster headache (CH) can present with migrainous symptoms such as nausea, photophobia, and phonophobia. In addition, an overlap between CH and migraine has been reported. This study aimed to determine the differences in the characteristics of CH according to the presence of comorbid migraine.
Learn More >To date, there have not been reliable biomarkers to identify impending migraine episodes. A prior study in adults with migraine demonstrated a reduction in the urinary metabolic substrate of melatonin (urinary 6-sulfatoxymelatonin; aMT6s) during a migraine. The aim of this study was to examine whether evening urinary melatonin metabolite levels could predict migraine the next day in children and adolescents with migraine.
Learn More >To inform migraine care model development by assessing differences between patients with chronic migraine (CM) and episodic migraine (EM) in the current state of treatment, disability, patient satisfaction, and quality improvement opportunities.
Learn More >Chronic postsurgical knee-pain (CPSP) is a burden for approx. 20% of the patients following total knee replacement (TKR). Presurgical pain intensities have consistently been found associated with CPSP and it is suggested that e.g. comorbidities are likewise important for development of CPSP. This study aimed to identify presurgical risk factors for development of CPSP 5 years after TKR based on medical records containing information regarding comorbidities.
Learn More >Repetitive transcranial magnetic stimulation (rTMS) at 5 Hz and 10 Hz is effective in improving pain, sleep quality, and anxiety among patients with postherpetic neuralgia (PHN). But it has not been reported which frequency is more effective and which frequency is safer.
Learn More >Based on previous clinic-based MRI studies showing regional differences in the cerebral cortex between those with and without headache, we hypothesized that headache sufferers have a decrease in volume, thickness or surface area in anterior cingulate cortex (ACC), prefrontal cortex (PFC), and insula. In addition, exploratory analyses on volume, thickness and surface area across the cerebral cortical mantle were performed. 1006 participants (50-66 years) from the general population were selected to an imaging study of the head at 1.5 T (HUNT-MRI). 283 individuals suffered from headache, 80 with migraine and 87 with tension-type headache, whereas 309 individuals did not suffer from headache and were used as controls. T1 weighted 3D scans of the brain were analysed with voxel-based morphometry and FreeSurfer. The association between cortical volume, thickness and surface area and questionnaire-based headache diagnoses was evaluated, taking into consideration evolution of headache and frequency of attacks. There were no significant differences in cortical volume, thickness or surface area between headache sufferers and non-sufferers in ACC, PFC or insula. Similarly, the exploratory analyses across the cortical mantle demonstrated no significant differences in volume, thickness or surface area between any of the headache groups and the non-sufferers. Maps of effect sizes showed small differences in the cortical measures between headache sufferers and non-sufferers. Hence, there are probably no or only very small differences in volume, thickness or surface area of the cerebral cortex between those with and without headache in the general population.
Learn More >Co-prevalence of chronic pain and post-traumatic stress disorder (PTSD) negatively impacts the course of both disorders. Patients diagnosed with both conditions report greater pain, affective distress and disability when compared to those with either chronic pain or PTSD alone. While the prevalence and complexity of the comorbidity is widely acknowledged, there is a dearth of research examining potential mechanism variables that might account for the relationship between chronic pain and PTSD. The current study utilizes a series of mediation analyses to examine if pain catastrophizing mediates the relationship between PTSD symptomatology and chronic pain outcome.
Learn More >Patients with high-frequency episodic migraine (HFEM) have a greater disease burden than those with low-frequency episodic migraine (LFEM). Acute treatment overuse increases the risk of migraine chronification in patients with HFEM. Galcanezumab, a humanized monoclonal antibody binding calcitonin gene-related peptide (CGRP), is effective for migraine prevention with a favorable safety profile. Here, we investigate whether there are differences in galcanezumab efficacy in patients with LFEM or with HFEM.
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