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nVNS sham significantly affects the trigeminal-autonomic reflex: A randomized controlled study.

To determine whether high placebo effects observed in recently published clinical noninvasive vagal nerve stimulation (nVNS) trials can be attributed to an active modulation of the trigeminal-autonomic reflex by the sham device.

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The relationship between hippocampal volume, chronic pain, and depressive symptoms in older adults.

We aimed to test the hypothesis that the effect of chronic pain on depressive symptoms is mediated through hippocampal volume (HV). Participants were 131 non-demented adults over the age of 70 years from the Einstein Aging Study. Smaller right and left HV were both associated with higher depressive symptoms, but only smaller right HV was associated with chronic pain. In mediation models, right HV was a significant mediator for the effect of chronic pain on depression. Our findings suggest presence of a shared brain substrates between chronic pain and depression as reflected by right HV.

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Anoctamin 3: A Possible Link between Cluster Headache and Ca Signaling.

Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic variants that were previously linked to verapamil response in migraine in a Swedish cluster headache case-control sample. We used TaqMan qPCR for genetic screening and performed a gene expression analysis on associated genes in patient-derived fibroblasts, and further investigated which reference genes were suitable for analysis in fibroblasts from cluster headache patients. We discovered a significant association between , a gene encoding a calcium-activated ion channel, and cluster headache. The association was not dependent on verapamil treatment since the associated variant, rs1531394, was also overrepresented in patients not using verapamil. No difference was found in the gene expression between controls and patients. Also, we determined that , and were suitable reference genes in cluster headache fibroblasts. This finding is the first report of an association between a variant in a gene encoding an ion-channel and cluster headache, and the first significant genetic evidence of calcium involvement in cluster headache pathophysiology.

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Altered synaptic adaptation and gain in sensory circuits of the casein kinase 1 delta (CK1dT44A) mouse model of migraine.

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Stem Cell Therapies for Treatment of Discogenic Low Back Pain: a Comprehensive Review.

Discogenic low back pain (DLBP) stems from pathology in one or more intervertebral discs identified as the root cause of the pain. It is the most common type of chronic low back pain (LBP), representing 26-42% of attributable cases.

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Bidirectional optogenetic modulation of prefrontal-hippocampal connectivity in pain-related working memory deficits.

Dysfunction of the prefrontal-hippocampal circuit has been identified as a leading cause to pain-related working-memory (WM) deficits. However, the underlying mechanisms remain poorly determined. To address this issue, we implanted multichannel arrays of electrodes in the prelimbic cortex (PL-mPFC), and in the dorsal hippocampal CA1 field (dCA1) to record the neural activity during the performance of a delayed non-match to sample (DNMS) task. The prefrontal-hippocampal connectivity was selectively modulated by bidirectional optogenetic inhibition or stimulation of local PL-mPFC glutamatergic calcium/calmodulin-dependent protein kinase-II alpha (CaMKIIα) expressing neurons during the DNMS task delay-period. The within-subject behavioral performance was assessed using a persistent neuropathic pain model – spared nerve injury (SNI). Our results showed that the induction of the neuropathic pain condition affects the interplay between PL-mPFC and dCA1 regions in a frequency-dependent manner, and that occurs particularly across theta oscillations while rats performed the task. In SNI-treated rats, this disruption was reversed by the selective optogenetic inhibition of PL-mPFC CaMKIIα-expressing neurons during the last portion of the delay-period, but without any significant effect on pain responses. Finally, we found that prefrontal-hippocampal theta connectivity is strictly associated with higher performance levels. Together, our findings suggest that PL-mPFC CaMKIIα-expressing neurons could be modulated by painful conditions and their activity may be critical for prefrontal-hippocampal connectivity during WM processing.

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The Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Fenobam: Pharmacokinetics, Side Effects, and Analgesic Effects in Healthy Human Subjects.

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Chronic Headache: a Review of Interventional Treatment Strategies in Headache Management.

To provide an overview of current interventional pain management techniques for primary headaches with a focus on peripheral nerve stimulation and nerve blocks.

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Off-label Antidepressant Use for Treatment and Management of Chronic Pain: Evolving Understanding and Comprehensive Review.

While clinicians have been using antidepressants for off-label indications in the treatment of chronic pain in recent years, newer studies have proven effectiveness and provided additional mechanistic understanding and defined potential adverse effects. As depression and chronic pain are frequently comorbid conditions, the use of antidepressants has allowed for treatment of both conditions concomitantly in the same patient population.

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Linking Traumatic Brain Injury, Sleep Disruption and Post-Traumatic Headache: a Potential Role for Glymphatic Pathway Dysfunction.

Traumatic brain injury (TBI) is a major public health concern in the USA and worldwide. Sleep disruption and headaches are two of the most common problems reported by patients after TBI. In this manuscript, we review the current knowledge regarding the relation between post-traumatic sleep disruption and headaches. We also describe the role of the glymphatic system as a potential link between TBI, sleep, and headaches.

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