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Intrathecal drug delivery systems (IDDSs) are used for the treatment of pain and spasticity. A wide range of educational criteria exist for these devices. The North American Neuromodulation Society (NANS) Education Committee developed a comprehensive IDDS curriculum to function as a standard for physician graduate education and assessment through training and into practice.
Learn More >The discovery of Mas-related G protein-coupled receptors (MRGPRs) in itch sensation promised a search for novel therapeutics of itch that ultimately met with little success. Recent structural determination of these receptors by Roth and Sun marks a big step forward in the search for therapeutics of debilitating itch.
Learn More >Altered periaqueductal gray matter (PAG) functional connectivity contributes to brain hyperexcitability in migraine. Although tryptophan modulates neurotransmission in PAG projections through its metabolic pathways, the effect of plasma tryptophan on PAG functional connectivity (PAG-FC) in migraine has not been investigated yet. In this study, using a matched case-control design PAG-FC was measured during a resting-state functional magnetic resonance imaging session in migraine without aura patients (n = 27) and healthy controls (n = 27), and its relationship with plasma tryptophan concentration (TRP) was assessed. In addition, correlations of PAG-FC with age at migraine onset, migraine frequency, trait-anxiety and depressive symptoms were tested and the effect of TRP on these correlations was explored. Our results demonstrated that migraineurs had higher TRP compared to controls. In addition, altered PAG-FC in regions responsible for fear-cascade and pain modulation correlated with TRP only in migraineurs. There was no significant correlation in controls. It suggests increased sensitivity to TRP in migraine patients compared to controls. Trait-anxiety and depressive symptoms correlated with PAG-FC in migraine patients, and these correlations were modulated by TRP in regions responsible for emotional aspects of pain processing, but TRP did not interfere with processes that contribute to migraine attack generation or attack frequency.
Learn More >Conservative management of cervical radiculopathy (CR) is a first treatment option as the risk-benefit ratio for surgery is less favorable. Systematic reviews and clinical practice guidelines reporting on the effectiveness of nonsurgical management have not considered the timing of management. The aim of this study was to establish consensus on effective nonsurgical treatment modalities at different stages (ie, acute, subacute or chronic) of CR, using the Delphi method approach.
Learn More >Mesenchyme homeobox protein 2 (MEOX2) is a transcription factor involved in mesoderm differentiation, including development of bones, muscles, vasculature and dermatomes. We have previously identified dysregulation of MEOX2 in fibroblasts from Congenital Insensitivity to Pain (CIP) patients, and confirmed that btn, the Drosophila homologue of MEOX2, plays a role in nocifensive responses to noxious heat stimuli. To determine the importance of MEOX2 in the mammalian peripheral nervous system, we used a Meox2 heterozygous (Meox2 ) mouse model to characterize its function in the sensory nervous system, and more specifically, in nociception. MEOX2 is expressed in the mouse dorsal root ganglia (DRG) and spinal cord, and localizes in the nuclei of a subset of sensory neurons. Functional studies of the mouse model, including behavioral, cellular and electrophysiological analyses, showed altered nociception encompassing impaired action potential initiation upon depolarization. Mechanistically, we noted decreased expression of Scn9a and Scn11a genes encoding Na 1.7 and Na 1.9 voltage gated sodium channels, respectively, that are crucial in subthreshold amplification and action potential initiation in nociceptors. Further transcriptomic analyses of Meox2 DRG revealed downregulation of a specific subset of genes including those previously associated with pain perception, such as PENK and NPY. Based on these observations, we propose a novel role of MEOX2 in primary afferent nociceptor neurons for the maintenance of a transcriptional program required for proper perception of acute and inflammatory noxious stimuli.
Learn More >The detailed pathological mechanism of orofacial neuropathic pain remains unknown. We aimed to examine the pannexin 1 (Panx1) signaling in the trigeminal ganglion (TG) involvement in infraorbital nerve injury (IONI)-induced orofacial neuropathic pain.
Learn More >Migraine is a common, chronic, disorder that is typically characterized by recurrent disabling attacks of headache and accompanying symptoms, including aura. The aetiology is multifactorial with rare monogenic variants. Depression, epilepsy, stroke and myocardial infarction are comorbid diseases. Spreading depolarization probably causes aura and possibly also triggers trigeminal sensory activation, the underlying mechanism for the headache. Despite earlier beliefs, vasodilation is only a secondary phenomenon and vasoconstriction is not essential for antimigraine efficacy. Management includes analgesics or NSAIDs for mild attacks, and, for moderate or severe attacks, triptans or 5HT receptor agonists. Because of cardiovascular safety concerns, unreliable efficacy and tolerability issues, use of ergots to abort attacks has nearly vanished in most countries. CGRP receptor antagonists (gepants) and lasmiditan, a selective 5HT1 receptor agonist, have emerged as effective acute treatments. Intramuscular onabotulinumtoxinA may be helpful in chronic migraine (migraine on ≥15 days per month) and monoclonal antibodies targeting CGRP or its receptor, as well as two gepants, have proven effective and well tolerated for the preventive treatment of migraine. Several neuromodulation modalities have been approved for acute and/or preventive migraine treatment. The emergence of new treatment targets and therapies illustrates the bright future for migraine management.
Learn More >In an attempt to aggregate observations from clinical trials, several meta-analyses have been published examining the effectiveness of systemic, non-opioid, pharmacological interventions to reduce the incidence of chronic postsurgical pain.
Learn More >Patients with chronic low back pain radiating to the leg (CLBPr) are sometimes referred to a specialised pain clinic for a precise diagnosis based, for example, on a diagnostic selective nerve root block. Possible interventions are therapeutic selective nerve root block or pulsed radiofrequency. Central pain sensitisation is not directly assessable in humans and therefore the term 'human assumed central sensitisation' (HACS) is proposed. The possible existence and degree of sensitisation associated with pain mechanisms assumed present in the human central nervous system, its role in the chronification of pain and its interaction with diagnostic and therapeutic interventions are largely unknown in patients with CLBPr. The aim of quantitative sensory testing (QST) is to estimate quantitatively the presence of HACS and accumulating evidence suggest that a subset of patients with CLBPr have facilitated responses to a range of QST tests.The aims of this study are to identify HACS in patients with CLBPr, to determine associations with the effect of selective nerve root blocks and compare outcomes of HACS in patients to healthy volunteers.
Learn More >P2X receptors are ATP-gated trimeric nonselective cation channels that are important for various physiological and pathological processes, including synaptic transmission, pain perception, immune regulation and apoptosis. Accordingly, they attract a wide range of interest as drug targets, such as those for chronic cough, neuropathic pain and depression. After the zebrafish P2X4 receptor structure was reported in 2009, various other P2X receptor structures have been reported, extending our understanding of the molecular mechanisms of P2X receptors. This review article describes the recent progress on understanding the structures and mechanisms of P2X receptors, especially of the mechanisms underlying ATP binding and conformational changes during the gating cycle. In addition, since several antagonists for different P2X subtypes have entered into clinical trials, this review also summarizes the binding sites and regulatory mechanisms of these antagonists, which may contribute to new strategies of targeting P2X receptors for drug discovery. This article is protected by copyright. All rights reserved.
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