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Neuroinflammation and periphery-to-CNS neuroimmune cross-talk in patients with painful knee osteoarthritis (OA) are poorly understood. We utilized proximity extension assay to measure the level of 91 inflammatory proteins in CSF and serum from OA patients and controls. The patients had elevated levels of 48 proteins in CSF indicating neuroinflammation. Ten proteins were correlated between CSF and serum and potentially involved in periphery-to-CNS neuroimmune cross-talk. Seven CSF proteins, all with previously reported neuroprotective effects, were associated with lower pain intensity and milder knee-related symptoms. Our findings indicate that neuroinflammation in OA could be protective and associated with less severe symptoms.
Learn More >Chronic pelvic pain (CPP), often defined as non-cyclical pelvic pain lasting for 6 months or longer, affects approximately 2-24% of women, depending on the CPP definition used (Daniels et al. BMJ 2010;341:c4834). While CPP can be a symptom associated with a variety of health conditions (including endometriosis, irritable bowel syndrome, and interstitial cystitis), at least 30% of women undergoing laparoscopic surgery have no associated disease diagnosis or clear pathologic cause for their pain.
Learn More >Veterans experience chronic pain at greater rates than the rest of society and are more likely to receive long-term opioid therapy (LTOT), which, at high doses, is theorized to induce maladaptive neuroplastic changes that attenuate self-regulatory capacity and exacerbate opioid dose escalation. Mindfulness meditation has been shown to modulate frontal midline theta (FMT) and alpha oscillations that are linked with marked alterations in self-referential processing. These adaptive neural oscillatory changes may promote reduced opioid use and remediate the neural dysfunction occasioned by LTOT. In this study, we used electroencephalography (EEG) to assess the effects of a mindfulness-based, cognitive training intervention for opioid misuse, mindfulness-oriented recovery enhancement (MORE), on alpha and theta power and FMT coherence during meditation. We then examined whether these neural effects were associated with reduced opioid dosing and changes in self-referential processing. Before and after 8 weeks of MORE or a supportive psychotherapy control, veterans receiving LTOT (N = 62) practiced mindfulness meditation while EEG was recorded. Participants treated with MORE demonstrated significantly increased alpha and theta power (with larger theta power effect sizes) as well as increased FMT coherence relative to those in the control condition-neural changes that were associated with altered self-referential processing. Crucially, MORE significantly reduced opioid dose over time, and this dose reduction was partially statistically mediated by changes in frontal theta power. Study results suggest that mindfulness meditation practice may produce endogenous theta stimulation in the prefrontal cortex, thereby enhancing inhibitory control over opioid dose escalation behaviors.Fig. 1SPECTRAL EEG CHANGES DURING A LABORATORY-BASED MINDFULNESS MEDITATION PRACTICE SESSION BEFORE AND AFTER 8 WEEKS OF MINDFULNESS-ORIENTED RECOVERY ENHANCEMENT (MORE) OR A SUPPORTIVE GROUP (SG) PSYCHOTHERAPY CONTROL CONDITION.: Topoplots are interpolated to cover the entire headspace. dB = decibels.Fig. 2THETA COHERENCE CHANGES DURING A LABORATORY-BASED MINDFULNESS MEDITATION PRACTICE SESSION BEFORE AND AFTER 8 WEEKS OF MINDFULNESS-ORIENTED RECOVERY ENHANCEMENT (MORE) OR A SUPPORTIVE GROUP (SG) PSYCHOTHERAPY CONTROL CONDITION.: Red colors indicate positive coherence while blue colors indicate negative coherence. Saturation of color as well as line thickness represent the strength of coherence between nodes. ROIs are grouped via node color. n.u. = normalized units.Fig. 3Path model indicating that the effect of mindfulness-oriented recovery enhancement (MORE) versus a supportive group (SG) psychotherapy control condition on reducing opioid dose was statistically mediated by increasing frontal theta power mindfulness meditation.Fig. 4Scatterplots depicting associations between treatment-related changes in frontal theta power and a self-transcendence (measured by the Nondual Awareness Dimensional Assessment) and b change in body boundaries (measured by the perceived body boundaries scale), among Veterans treated with mindfulness-oriented recovery enhancement (MORE) or a supportive group (SG) psychotherapy condition.
Learn More >To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study.
Learn More >Several single-nucleotide polymorphisms (SNPs) are associated with restless legs syndrome (RLS). This study investigated whether or not additional SNP variants increase the risk of RLS in migraineurs and in migraine with aura (MA) and migraine without aura (MoA) subgroups.
Learn More >Cytochrome P450 2D (CYP2D) mediates the activation and inactivation of several classes of psychoactive drugs, including opioids, which can alter drug response. Tramadol is a synthetic opioid with analgesic activity of its own as well as being metabolically activated by CYP2D to O-desmethyltramadol (ODMST) an opioid receptor agonist. We investigated the impact of brain CYP2D metabolism on central tramadol and ODSMT levels, and resulting analgesic response after oral tramadol administration in rats. CYP2D inhibitors propranolol and propafenone were administered intracerebroventricularly prior to oral tramadol administration and analgesia was measured by tail-flick latency. Drug levels of tramadol and its metabolites, ODSMT and N-desmethyltramadol, were assessed in plasma and in brain by microdialysis using LC-ESI-MS/MS. Inhibiting brain CYP2D with propafenone pretreatment increased analgesia after oral tramadol administration (ANOVA p = 0.02), resulting in a 1.5-fold increase in area under the analgesia-time curve (AUC, p < 0.01). This effect was associated with changes in the brain levels of tramadol and its metabolites consistent with brain CYP2D inhibition. In conclusion, under oral tramadol dosing pretreatment with a central administration of the CYP2D inhibitor propafenone increased analgesia (without altering plasma drug or metabolite levels), indicating that tramadol itself (and activity of CYP2D within the brain) contributed to analgesia.
Learn More >The present study was undertaken to further investigate the spinal anti-allodynic effects of endomorphins (EMs) and their C-terminal hydrazide modified analogs EM-1-NHNH and EM-2-NHNH in the spared nerve injury (SNI) model of neuropathic pain in mice. Our results demonstrated that intrathecal (i.t.) administration of endomorphin-1 (EM-1), endomorphin-2 (EM-2), EM-1-NHNH and EM-2-NHNH produced potent anti-allodynic effects ipsilaterally in neuropathic pain model. Judging from the area under the curve (AUC) values, these two analogs exhibited higher antinociception than their parent peptides. Moreover, they also displayed significant antinociceptive effects in the contralateral paw administered intrathecally. Interestingly, EM-1 and its analog EM-1-NHNH displayed their antinociception probably by μ-opioid receptor subtype since the μ-opioid receptor antagonist naloxonazine didn't significantly block the anti-allodynia of EM-1 and EM-1-NHNH, which implied a same opioid mechanism. However, the anti-allodynia induced by EM-2, but not EM-2-NHNH was significantly reduced by both μ-opioid antagonist, naloxonazine and κ-antagonist, nor-binaltorphamine (nor-BNI), indicating multiple opioid receptors were involved in the anti-allodynic effects of EM-2. Most importantly, EM-1-NHNH decreased the antinociceptive tolerance, and EM-2-NHNH displayed non-tolerance-forming antinociception. Therefore, C-terminal amide to hydrazide conversion changed the spinal antinociceptive profiles of EMs in neuropathic pain. The present investigation is of great value in the development of novel opioid therapeutics against neuropathic pain.
Learn More >Loss-adjusting: Young People’s Constructions of a Future Living with Complex Regional Pain Syndrome.
Complex Regional Pain Syndrome (CRPS) is a chronic pain condition that can present specific difficulties when occurring in adolescence. There is limited work exploring future narratives of healthy adolescents, and how these may differ for those who have chronic health conditions, but there is no research on the future narratives of adolescents who have CRPS.
Learn More >Multisite chronic pain (MSCP) is associated with increased chronic pain impact, but methods for identifying MSCP for epidemiological research have not been evaluated.
Learn More >The primary aim was to quantify and compare the location and extent of pain in people with either episodic migraine, chronic migraine, or cervicogenic headache. A secondary aim was to examine the associations between pain extent and headache features, quality of life, and psychological distress for each headache type.
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