Browse by Audience
This study was to assess the clinical efficacy of epidural injections with tumor necrosis factor-alpha (TNF-α) inhibitor in patients with chronic radicular pain caused by lumbar spinal stenosis (LSS). In a randomized controlled trial (RCT), patients diagnosed with mild-to-moderate LSS underwent epidural intervention with three different drugs and were allocated to TNF-α inhibitor group (Group A), steroid group (Group B) and lidocaine-only group (Group C). All patients were evaluated by visual analog scale (VAS) for leg pain and Oswestry disability index (ODI) to assess function. They all received a 6-month follow-up. Ninety patients were randomly assigned to three groups, for 30 cases in each group. A total of 82 participants (91.1%) completed the follow-up. Pain relief and improvement of movement function after epidural administration in Group A were more significant than those of groups B and C ( < .05) during the 6-month follow-up, while it showed no significant difference between groups B and C ( > .05). Our results indicated that epidural administration with TNF-α inhibitor may be a useful conservative method for the treatment of radicular pain caused by LSS. ClinicalTrials.gov Identifier: NCT04062474.
Learn More >Pain is frequent in multiple sclerosis (MS) and includes different types, with neuropathic pain (NP) being most closely related to MS pathology. However, prevalence estimates vary largely, and causal relationships between pain and biopsychosocial factors in MS are largely unknown. Longitudinal studies might help to clarify the prevalence and determinants of pain in MS. To this end, we analyzed data from 410 patients with newly diagnosed clinically isolated syndrome or relapsing-remitting MS participating in the prospective multicenter German National MS Cohort Study (NationMS) at baseline and after 4 years. Pain was assessed by self-report using the PainDETECT Questionnaire. Neuropsychiatric assessment included tests for fatigue, depression, and cognition. In addition, sociodemographic and clinical data were obtained. Prevalence of pain of any type was 40% and 36% at baseline and after 4 years, respectively, whereas prevalence of NP was 2% and 5%. Pain of any type and NP were both strongly linked to fatigue, depression, and disability. This link was even stronger after 4 years than at baseline. Moreover, changes in pain, depression, and fatigue were highly correlated without any of these symptoms preceding the others. Taken together, pain of any type seems to be much more frequent than NP in early nonprogressive MS. Moreover, the close relationship between pain, fatigue, and depression in MS should be considered for treatment decisions and future research on a possible common pathophysiology.
Learn More >Among painful disorders, migraine is distinguishable by its chronic pathology and episodic clinical manifestation. Only a small percentage of patients with migraine progress to a chronic form of migraine. Both peripheral and central portions of the trigeminal system are involved in the pathophysiology of migraine pain, as they are involved in the processes of peripheral and central sensitization, alongside various subcortical and cortical brain structures. This review focuses on clinical, neurophysiological, and neuroimaging data underscoring cortical pain processing in migraine. Data obtained from quantitative sensory testings are inconclusive and support the involvement of the peripheral portion of the trigeminovascular system as indirect evidence of peripheral sensitization, solely during the headache phase. The assessment of subjective pain intensity in response to several painful modalities has not been conclusive for the clear state of central sensitization in between migraine attacks but for the subclinical allodynia state that defines the boundary between behavioural responses and an irritable nervous state. Modulation of the brainstem and midbrain pain pathways, in conjunction with the thalamic and thalamocortical pathways, may be critical for the initiation and maintenance of migraine attacks. Several studies using different neuroimaging techniques have demonstrated that brains experiencing migraine undergo plastic changes in both microstructure and macrostructure and in the functioning of cortical networks, which may manifest early in the life of a patient with migraine. Further studies are required to understand how specific these results are to migraine relative to other painful disorders.
Learn More >This study aims to investigate whether intra-network dynamic functional connectivity and causal interactions of the salience network is altered in the interictal term of migraine. 32 healthy controls, 37 migraineurs without aura and 20 migraineurs with aura were recruited. Participants underwent a T1-weighted scan and resting-state fMRI protocol inside a 1.5T MR scanner. We obtained average spatial maps of resting-state networks using group independent component analysis, which yielded subject-specific time series via a dual regression approach. Salience network ROIs (bilateral insulae and prefrontal cortices, dorsal anterior cingulate cortex) were obtained from the group average map via cluster-based thresholding. To describe intra-network connectivity, average and dynamic conditional correlation was calculated. Causal interactions between the default-mode, dorsal attention and salience network were characterised by spectral Granger's causality. Time-averaged correlation was lower between the right insula and prefrontal cortex in migraine without aura vs. with aura and healthy controls (p<0.038, p<0.037). Variance of dynamic conditional correlation was higher in migraine with aura vs. healthy controls and migraine with aura vs. without aura between the right insula and dorsal anterior cingulate cortex (p<0.011, p<0.026), and in migraine with aura vs. healthy controls between the dorsal anterior cingulate and left prefrontal cortex (p<0.021). Causality was weaker in the <0.05 Hz frequency range between the salience and dorsal attention networks in migraine with aura (p<0.032). Overall, migraineurs with aura exhibit more fluctuating connections in the salience network, which also affect network interactions, and could be connected to altered cortical excitability and increased sensory gain.
Learn More >Lasmiditan is a centrally penetrant, highly selective 5-hydroxytryptamine (serotonin) receptor 1F (5HT ) agonist under development as a novel therapy for acute treatment of migraine. A phase 1 randomized, placebo- and positive-controlled crossover study assessed the abuse potential of lasmiditan in adult recreational polydrug users. Following a qualification phase, subjects were randomized into treatment sequences, each consisting of 5 study treatments: placebo, alprazolam 2 mg, lasmiditan 100, 200 (lasmiditan 100 and 200 mg are proposed therapeutic doses), and 400 mg (supratherapeutic). The abuse potential of lasmiditan was investigated and compared with alprazolam and with placebo using the maximal effect score (E ) of the Drug-Liking Visual Analog Scale as the primary end point. Lasmiditan was not similar to placebo in drug-liking scores at all doses tested, with a maximum difference observed with the lasmiditan 400-mg dose (upper 90% confidence limit on difference in least-squares [LS] means > 14 for all lasmiditan doses). Drug-liking scores for lasmiditan 400 mg were not significantly different from alprazolam (lower 90% confidence limit on difference in LS means < 5), but drug-liking scores at lower doses (100 and 200 mg) were significantly different from alprazolam. During the treatment phase, the incidence of treatment-emergent adverse events (TEAEs) increased with increasing dose of lasmiditan; all TEAEs reported with lasmiditan treatment were mild. Subjective drug-liking effects for lasmiditan versus placebo and versus alprazolam, and the safety and tolerability profile of lasmiditan suggest that lasmiditan has a low potential for abuse.
Learn More >Genome-wide association studies have implicated dozens of genes with migraine susceptibility, but it remains unclear in which nervous system cell types these genes are expressed.
Learn More >Because abnormal activity of the autonomic nervous system is associated with chronification of pain, early detection of such dysfunction is important.
Learn More >Opioids have, at most, small benefits for non-cancer pain in the medium and long-term but there is good evidence that they cause harm. The current study describes the characteristics and clinical status of people taking regular opioids in Great Britain and determines whether use is associated with mortality risk.
Learn More >High-frequency stimulation (HFS) of the sciatic nerve has been reported to produce long-term potentiation (LTP) and long-lasting pain hypersensitivity in rats. However, the central underlying mechanism remains unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) belongs to a group of electron-transporting transmembrane enzymes that produce reactive oxygen species (ROS). Here, we found that NOX2 was upregulated in the lumbar spinal dorsal horn after HFS of the left sciatic nerve, which induced bilateral pain and spinal LTP in both male and female rats. Blocking NOX2 with blocking peptide or shRNA prevented the development of bilateral mechanical allodynia, the induction of spinal LTP, and the phosphorylation of N-methyl-d-aspartate (NMDA) receptor 2B (GluN2B) and nuclear factor kappa-B (NF-κB) p65 after HFS. Moreover, NOX2 shRNA reduced the frequency and amplitude of both spontaneous excitatory postsynaptic currents and miniature excitatory postsynaptic currents in laminar II neurons. Furthermore, 8-hydroxyguanine (8-OHG), an oxidative stress marker, was increased in the spinal dorsal horn. Spinal application of ROS scavenger, Phenyl-N-tert-butylnitrone (PBN), depressed the already established spinal LTP. Spinal application of H2O2, one ROS, induced LTP and bilateral mechanical allodynia, increased the frequency and amplitude of spontaneous excitatory postsynaptic currents in laminar II neurons, and phosphorylated GluN2B and p65 in the dorsal horn. This study provided electrophysiological and behavioral evidence that NOX2-derived ROS in the spinal cord contributed to persistent mirror-image pain by enhancing the synaptic transmission, which was mediated by increasing presynaptic glutamate release and activation of NMDA receptor and NF-κB in the spinal dorsal horn.
Learn More >