Browse by Audience
Sodium valproate (VPA) has analgesic effects in clinical and experimental studies, but the mechanisms are still unclear. The present study examined the effects of VPA on stress-induced somatic hyperalgesia and visceral hypersensitivity and the role of 5-HT receptors in the spinal cord. Repeated 3 day forced swim (FS) significantly reduced the thermal withdrawal latency and mechanical withdrawal threshold, and increased the magnitude of the visceromotor response to colorectal distention compared to the baseline values in rats. The somatic hyperalgesia and visceral hypersensitivity were accompanied by significant down-regulation of 5-HT receptor expression in the L4-L5 and L6-S1 dorsal spinal cord. Intraperitoneal administration of VPA (300 mg/kg) before each FS and 1 day post FS prevented the development of somatic hyperalgesia and visceral hypersensitivity induced by FS stress, as well as down-regulation of 5-HT receptors in the spinal cord. The reversal of somatic hyperalgesia and visceral hypersensitivity by VPA in FS rats was blocked by intrathecal administration of the selective 5-HT receptor antagonist RS-102221 (30 μg/10 μL) 30 min after each VPA injection. The results suggest that VPA attenuates FS-induced somatic hyperalgesia and visceral hypersensitivity by restoring down-regulated function of 5-HT receptors in the spinal cord.
Learn More >Do measures of state anxiety and trait anxiety in people with acute low back pain (ALBP) improve prediction of chronic low back pain (CLBP), defined as pain or pain-related disability at 12 weeks?
Learn More >It is increasingly recognized that chronic opioid use leads to maladaptive changes in the composition and localization of gut bacteria. Recently, this "opioid-induced dysbiosis" (OID) has been linked to antinociceptive tolerance development in preclinical models and may therefore identify promising targets for new opioid-sparing strategies. Such developments are critical to curb dose escalations in the clinical setting and combat the ongoing opioid epidemic. In this article, we review the existing literature that pertains to OID, including the current evidence regarding its qualitative nature, influence on antinociceptive tolerance, and future prospects. Perspective: This article reviews the current literature on opioid-induced dysbiosis (OID) of gut bacteria, including its qualitative nature, influence on antinociceptive tolerance, and future prospects. This work may help identify targets for new opioid-sparing strategies.
Learn More >Dysfunctional top-down pain modulation is a hallmark of fibromyalgia (FM) and physical exercise is a cornerstone in FM treatment. The aim of this study was to explore the effects of a 15-week intervention of strengthening exercises, twice per week, supervised by a physiotherapist, on exercise-induced hypoalgesia (EIH) and cerebral pain processing in FM patients and healthy controls (HC). FM patients (n = 59) and HC (n = 39) who completed the exercise intervention as part of a multicenter study were examined at baseline and following the intervention. Following the exercise intervention, FM patients reported a reduction of pain intensity, fibromyalgia severity and depression. Reduced EIH was seen in FM patients compared to HC at baseline and no improvement of EIH was seen following the 15-week resistance exercise intervention in either group. Furthermore, a subsample (Stockholm site: FM = 18; HC = 19) was also examined with functional magnetic resonance imaging (fMRI) during subjectively calibrated thumbnail pressure pain stimulations at baseline and following intervention. A significant main effect of exercise (post > pre) was observed both in FM patients and HC, in pain-related brain activation within left dorsolateral prefrontal cortex and caudate, as well as increased functional connectivity between caudate and occipital lobe bordering cerebellum (driven by the FM patients). In conclusion, the results indicate that 15-week resistance exercise affect pain-related processing within the cortico-striatal-occipital networks (involved in motor control and cognition), rather than directly influencing top-down descending pain inhibition. In alignment with this, exercise-induced hypoalgesia remained unaltered.
Learn More >Many patients with chronic pain use prescription opioids. Epigenetic modification of the μ-opioid receptor 1 () gene, which codes for the target protein of opioids, may influence vulnerability to opioid abuse and response to opioid pharmacotherapy, potentially affecting pain outcomes.
Learn More >It is unknown if physiological changes associated with chronic pain could be measured with inexpensive physiological sensors. Recently, acute pain and laboratory-induced pain have been quantified with physiological sensors.
Learn More >Chronic migraine is characterised by persistent headaches for >15 days per month; the intensity of the pain is fluctuating over time. Here, we explored the dynamic interplay of connectivity patterns between regions known to be related to pain processing and their relation to the ongoing dynamic pain experience. We recorded EEG from 80 sessions (20 chronic migraine patients in 4 separate sessions of 25 min). The patients were asked to continuously rate the intensity of their endogenous headache. On different time-windows, a dynamic causal model (DCM) of cross spectral responses was inverted to estimate connectivity strengths. For each patient and session, the evolving dynamics of effective connectivity were related to pain intensities and to pain intensity changes by using a Bayesian linear model. Hierarchical Bayesian modelling was further used to examine which connectivity-pain relations are consistent across sessions and across patients. The results reflect the multi-facetted clinical picture of the disease. Across all sessions, each patient with chronic migraine exhibited a distinct pattern of pain intensity-related cortical connectivity. The diversity of the individual findings are accompanied by inconsistent relations between the connectivity parameters and pain intensity or pain intensity changes at group level. This suggests a rejection of the idea of a common neuronal core problem for chronic migraine.
Learn More >Treatment with baricitinib in combination with topical corticosteroids previously showed greater improvements in itch and sleep versus placebo in adults with moderate-to-severe AD.
Learn More >Recent studies suggested that epigenetic mechanisms, including DNA methylation, may be involved in migraine pathogenesis. The calcitonin gene-related peptide (CGRP), encoded by calcitonin gene-related peptide 1 gene, plays a key role in the disease. The aim of the study was to evaluate DNA methylation of gene in patients with episodic migraine. 22 patients with episodic migraine (F/M 15/7, mean age 39.7 ± 13.4 years) and 20 controls (F/M 12/8, mean age 40.5 ± 14.8 years) were recruited. Genomic DNA was extracted from peripheral blood. Cytosine-to-thymine conversion was obtained with sodium bisulfite. The methylation pattern of two CpG islands in the promoter region of gene was analyzed. No difference of methylation of the 30 CpG sites at the distal region of promoter was observed between migraineurs and controls. Interestingly, in patients with episodic migraine the methylation level was lower in 2 CpG sites at the proximal promoter region (CpG -1461, p = 0.037, and -1415, p = 0.035, respectively). Furthermore, DNA methylation level at different CpG sites correlates with several clinical characteristics of the disease, as age at onset, presence of nausea/vomiting, depression and anxiety (p < 0.05). In conclusion, we found that DNA methylation profile in two CpG sites at the proximal promoter region of is lower in migraineurs when compared to controls. Intriguingly, the -1415 hypomethylated unit is located at the CREB binding site, a nuclear transcription factor. In addition, we found a correlation between the level of methylation and several clinical features of migraine. Further studies with larger sample size are needed to confirm these results.
Learn More >