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Botulinum Toxin Type A for refractory trigeminal neuralgia in older patients: a better therapeutic effect.

Some studies have indicated that a local injection of Botulinum Toxin Type A (BTX-A) is a promising therapy for trigeminal neuralgia (TN). However, BTX-A treatment is still ineffective for approximately 10-43% of patients. We therefore investigated which factors are associated with the therapeutic effect in BTX-A treatment of medically refractory, classical TN.

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Response Predictors in Chronic Migraine: Medication Overuse and Depressive Symptoms Negatively Impact Onabotulinumtoxin-A Treatment.

Despite numerous studies that have investigated clinical, radiological, and biochemical response predictors, the clinical profile of those patients who might benefit from OnabotulinumtoxinA is still missing. The aim of the present study was to identify potential OnabotulinumtoxinA response predictors among several clinical characteristics and confirm OnabotulinumtoxinA efficacy and safety in chronic migraine (CM) prevention. The study was conducted at the Headache Center-Neurology Clinic-Spedali Civili Hospital of Brescia. Eighty-four consecutive CM patients were enrolled, with a mean age of 48 years (SD 9.7) and a mean disease duration of 10.1 years (SD 6.6). The mean reported headache-days frequency was 22.5 (SD 5.9) per month, while the mean number of severe headache-days was 15.2 (SD 8.9) with a mean monthly medication intake of 33.2 (SD 5.6). The clinical characteristics analyzed as potential response predictors were: gender, disease duration, migraine characteristics (location, side constancy, unilateral autonomic and neurovegetative symptoms), previous prophylactic treatments, add-on therapies, withdrawal therapies, psychiatric (anxiety and depression symptoms) comorbidities and medication overuse. A significant reduction from baseline to 3, 6, 9, and 12 month treatment cycles in total headache days, high intensity headache days and triptans consumption per month was found. Depressive symptoms and medication overuse negatively predicted OnabotulinumtoxinA outcome. Our results confirm the efficacy and safety of OnabotulinumtoxinA in CM. Depressive comorbidity and medication overuse, among all clinical variables, were the only significant response predictors. Such findings provide interesting insights regarding patients selection for OnabotulinumtoxinA treatment as, with the introduction of anti calcitonin gene-related (CGRP) monoclonal antibodies, clinicians will have to thoroughly judge and tailor among the many available therapeutic options now available. Future research might be needed to confirm our findings, in particular for its therapeutic implications.

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Anxiety-induced hyperalgesia in female rats is mediated by cholecystokinin 2 receptor in rostral ventromedial medulla and spinal 5-hydroxytryptamine 2B receptor.

Preoperative anxiety is associated with postoperative hyperalgesia; however, few studies have investigated the mechanism underlying this association in female surgical patients. Research has suggested that ON cells in the rostral ventromedial medulla (RVM) receive nerve impulses via cholecystokinin 2 (CCK2) receptors, facilitating hyperalgesia. Additionally, the downstream serotonergic projection system from the RVM to the spinal cord has a dual regulating effect on pain responses, and the 5-hydoxytryptophan 2B (5-HT2B) receptor in spinal dorsal horn neurons is critically involved in mechanical allodynia.

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Novel Characterization Of Thermal Temporal Summation Response By Analysis Of Continuous Pain Vs Time Curves And Exploratory Modeling.

Temporal summation (TS) refers to the increased perception of pain with repetitive noxious stimuli. While thermal TS is generally considered a behavioral correlate of spinal windup, noxious heat pulses also trigger additional sensory processes which were modeled in this study.

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Analgesic Effects of Compression at Trigger Points Are Associated With Reduction of Frontal Polar Cortical Activity as Well as Functional Connectivity Between the Frontal Polar Area and Insula in Patients With Chronic Low Back Pain: A Randomized Trial.

Compression of myofascial trigger points (MTrPs) in muscles is reported to reduce chronic musculoskeletal pain. Although the prefrontal cortex (PFC) is implicated in development of chronic pain, the mechanisms of how MTrP compression at low back regions affects PFC activity remain under debate. In this study, we investigated effects of MTrP compression on brain hemodynamics and EEG oscillation in subjects with chronic low back pain.

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Alterations in grey matter density and functional connectivity in trigeminal neuropathic pain and trigeminal neuralgia: A systematic review and meta-analysis.

Various studies reported changes in grey matter volumes and modifications in functional connectivity of cortical and subcortical structures in patients suffering from trigeminal neuralgia (TN) and trigeminal neuropathic pain (TNP). This study meta-analyzed the concordant structural and functional changes in foci and provide further understanding of the anatomy and biology of TN/TNP.

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Modular organization of brain resting state networks in patients with classical trigeminal neuralgia.

The modular organization of brain networks in trigeminal neuralgia patients has remained largely unknown. We aimed to analyze the brain modules and intermodule connectivity in patients with trigeminal neuralgia before and after percutaneous radiofrequency rhizotomy treatment to identify specific modules that may be associated with the development and brain plasticity of trigeminal neuralgia and to test the ability of modularity analysis to be a predictive imaging biomarker for the treatment effect in patients with trigeminal neuralgia.

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Pharmacological Blockade of Spinal CXCL3/CXCR2 Signaling by NVP CXCR2 20, a Selective CXCR2 Antagonist, Reduces Neuropathic Pain Following Peripheral Nerve Injury.

Recently, the role of CXCR2 in nociception has been noted. Our studies provide new evidence that the intrathecal administration of its CINC ligands (Cytokine-Induced Neutrophil Chemoattractant; CXCL1-3) induces pain-like behavior in naïve mice, and the effect occurring shortly after administration is associated with the neural location of CXCR2, as confirmed by immunofluorescence. RT-qPCR analysis showed, for the first time, raised levels of spinal CXCR2 after chronic constriction injury (CCI) of the sciatic nerve in rats. Originally, on day 2, we detected escalated levels of the spinal mRNA of all CINCs associated with enhancement of the protein level of CXCL3 lasting until day 7. Intrathecal administration of CXCL3 neutralizing antibody diminished neuropathic pain on day 7 after CCI. Interestingly, CXCL3 is produced in lipopolysaccharide-stimulated microglial, but not astroglial, primary cell cultures. We present the first evidence that chronic intrathecal administrations of the selective CXCR2 antagonist, NVP CXCR2 20, attenuate neuropathic pain symptoms and CXCL3 expression after CCI. Moreover, in naïve mice, this antagonist prevented CXCL3-induced hypersensitivity. However, NVP CXCR2 20 did not diminish glial activation, thus not enhancing morphine/buprenorphine analgesia. These results provide novel insight into the crucial role of CXCR2 in neuropathy based on CXCL3 modulation, which may become a potential therapeutic target in pain treatment.

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Central Neuropathic Pain and Profiles of Quantitative Electroencephalography in Multiple Sclerosis Patients.

Pain has a significant impact on the quality of life of patients with multiple sclerosis (MS). However, the neurophysiological mechanisms of central neuropathic pain in a MS course are not known. We hypothesized that changes in power spectral density (PSD) that take place in the electroencephalography (EEG) of MS patients with and without the central neuropathic pain (CNP) would differ. The study aimed to assess the features of quantitative EEG using the PSD indicator along with peak frequencies in the standard frequency bands in MS patients with and without CNP. We have analyzed the quantitative spectral content of the EEG at a resting state in 12 MS patients with CNP, 12 MS patients without CNP, and 12 gender- and age-matched healthy controls using fast Fourier transformation. Based on the ANOVA, at the group level, the theta band absolute and relative PSD showed an increase, whereas alpha band relative PSD showed a decrease in MS patients both with and without CNP. However, only in MS with CNP group, the absolute and relative PSD in the beta1 and beta2 bands increased and exceeded that in patients without pain. Only MS patients with CNP demonstrated the significantly increased absolute PSD for the theta, beta1, and beta2 frequency bands in most regions of interest. In the theta band, MS patients with CNP displayed the increase in absolute spectral power for the mid-temporal derivation of the right hemisphere and the increase in relative spectral power for the prefrontal derivation of this hemisphere. In the beta1 band, the increase in absolute spectral power was observed for the three temporal derivations of the right hemisphere, whereas in the beta2 band, for the occipital, parietal, and temporal lobes of both hemispheres. In the alpha band, only a relative spectral power decrease was revealed for the occipital lobes of both hemispheres and parietal lobe of the right hemisphere. In MS patients with CNP, the frequencies of the dominant spectral power (peak frequencies) in the high-frequency beta band were higher than in the healthy control in posterior areas of the left hemisphere. Data could represent central nervous system alterations related to central neuropathic pain in MS patients that lead to the disturbances in cortical communication.

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Editorial: Resilience Resources in Chronic Pain Patients: The Path to Adaptation.

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