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Comparing objective cognitive impairments in patients with peripheral neuropathic pain or fibromyalgia.

Existing studies on cognitive impairments in chronic pain do not investigate peripheral neuropathic pain (PNP) or compare pain conditions in a satisfactory manner. Here we aimed to compare executive dysfunctions in PNP patients with fibromyalgia (FM) and healthy controls (HC). Patients who self-reported cognitive impairments were assessed according to criteria for PNP or FM. Seventy-three patients met criteria and completed testing on executive functioning and IQ measures. We also included twenty matched healthy controls. Regression models controlling for age, sex and IQ, tested associations between group category (PNP, FM or HC) and outcomes. If a substantial association was detected, we followed up with head-to-head comparisons between PNP and FM. Multivariate regression models then tested associations between executive functioning and pain type, controlling for significant confounders. Results from head-to-head comparison between pain conditions showed significant differences on years lived with pain (FM > PNP), the use of anticonvulsants (PNP > FM) and use of analgesics (PNP > FM). When controlled for all significant differences, PNP patients had significantly lower scores on an attention-demanding cued-recall task compared to FM. Poor performance on attention-demanding cued-recall task was associated with PNP, which translate into problems with retaining fast-pace or advanced information.

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Association of nocebo hyperalgesia and basic somatosensory characteristics in a large cohort.

Medical outcomes are strongly affected by placebo and nocebo effects. Prediction of who responds to such expectation effects has proven to be challenging. Most recent approaches to prediction have focused on placebo effects in the context of previous treatment experiences and expectancies, or personality traits. However, a recent model has suggested that basic somatosensory characteristics play an important role in expectation responses. Consequently, this study investigated not only the role of psychological variables, but also of basic somatosensory characteristics. In this study, 624 participants underwent a placebo and nocebo heat pain paradigm. Additionally, individual psychological and somatosensory characteristics were assessed. While no associations were identified for placebo responses, nocebo responses were associated with personality traits (e.g. neuroticism) and somatosensory characteristics (e.g. thermal pain threshold). Importantly, the associations between somatosensory characteristics and nocebo responses were among the strongest. This study shows that apart from personality traits, basic somatosensory characteristics play an important role in individual nocebo responses, in agreement with the novel idea that nocebo responses result from the integration of top-down expectation and bottom-up sensory information.

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The impact of Pain-related emotions on migraine.

The response to pain is highly individual and can be influenced by complex emotional perception. This study aims to investigate the status of the pain-related emotional response, and the influence on headache characteristics and disability in migraine. We studied the pain-related emotional response in 145 consecutive migraine patients using the Pain Anxiety Symptoms Scale (PASS), the Pain Catastrophizing Scale (PCS), and the Pain Sensitivity Questionnaire (PSQ) and compared them with 106 healthy controls. We investigated the relationship between emotional factors and migraine characteristics. The effect of pain-related emotion on migraine-related disability assessed with the Headache Impact Test-6 (HIT-6) and the Migraine Disability Assessment (MIDAS). Migraine patients showed significantly higher scores on total PASS (p < 0.001), PCS (p < 0.001) and PSQ (p = 0.002) compared to the healthy controls. The HIT-6 was weakly correlated with PASS (r = 0.390, p < 0.001) and PCS (r = 0.354, p < 0.001). PASS-Total (p = 0.001), headache frequency (p = 0.003), and HADS-Anxiety (p = 0.028) were independent variables associated with HIT-6. Headache frequency (p < 0.001) was an independent variable associated with MIDAS. The structural equation model indicated that headache severity has direct loading on emotion and subsequently influenced migraine-related disability. Disability has a significant effect on the frequency of abortive medication use. Migraine patients have altered emotional responses to pain perception. Pain-related anxiety made an important contribution to headache-related disability. The present results suggest that the management of disability by considering various pain-related emotional factors may be necessary for the therapeutic aspects of migraine.

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Safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation: Analysis of the WHO pharmacovigilance database.

To assess the safety profile of erenumab, galcanezumab and fremanezumab in pregnancy and lactation.

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Use of medicinal plants for headache, and their potential implication in medication-overuse headache: Evidence from a population-based study in Nepal.

In Nepal, traditional treatment using medicinal plants is popular. Whereas medication-overuse headache is, by definition, caused by excessive use of acute headache medication, we hypothesized that medicinal plants, being pharmacologically active, were as likely a cause.

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The Complex Association Between Pain And Neuropathy.

Several studies of patients with polyneuropathy failed to show differences between patients with and without pain. In the current study, we aimed to explore the association between neuropathic symptoms, mainly pain, and polyneuropathy characteristics.

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Kratom Alkaloids, Natural and Semi-Synthetic, Show Less Physical Dependence and Ameliorate Opioid Withdrawal.

Chronic administration of opioids produces physical dependence and opioid-induced hyperalgesia. Users claim the Thai traditional tea "kratom" and component alkaloid mitragynine ameliorate opioid withdrawal without increased sensitivity to pain. Testing these claims, we assessed the combined kratom alkaloid extract (KAE) and two individual alkaloids, mitragynine (MG) and the analog mitragynine pseudoindoxyl (MP), evaluating their ability to produce physical dependence and induce hyperalgesia after chronic administration, and as treatments for withdrawal in morphine-dependent subjects. C57BL/6J mice (n = 10/drug) were administered repeated saline, or graded, escalating doses of morphine (intraperitoneal; i.p.), kratom alkaloid extract (orally, p.o.), mitragynine (p.o.), or MP (subcutaneously, s.c.) for 5 days. Mice treated chronically with morphine, KAE, or mitragynine demonstrated significant drug-induced hyperalgesia by day 5 in a 48 °C warm-water tail-withdrawal test. Mice were then administered naloxone (10 mg/kg, s.c.) and tested for opioid withdrawal signs. Kratom alkaloid extract and the two individual alkaloids demonstrated significantly fewer naloxone-precipitated withdrawal signs than morphine-treated mice. Additional C57BL/6J mice made physically dependent on morphine were then used to test the therapeutic potential of combined KAE, mitragynine, or MP given twice daily over the next 3 days at either a fixed dose or in graded, tapering descending doses. When administered naloxone, mice treated with KAE, mitragynine, or MP under either regimen demonstrated significantly fewer signs of precipitated withdrawal than control mice that continued to receive morphine. In conclusion, while retaining some liabilities, kratom, mitragynine, and mitragynine pseudoindoxyl produced significantly less physical dependence and ameliorated precipitated withdrawal in morphine-dependent animals, suggesting some clinical value.

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Future in regional anesthesia and pain medicine: the pharmacological view.

Local anesthetics are still incompletely understood, and none of the currently available drugs are optimal. The primary target of local anesthetics is the voltage-gated sodium channel (VGSC), where they lead to a temporary interruption of nerve conduction. Unfortunately, local anesthetics are neither specific at blocking a specific VGSC isoform, nor a specific cell type. We realize now that the old classification of A and C fibers according to myelin thickness is outdated, that next to differing myelin configuration, cells differ also by their molecular biology, and that there are close to 20 different neuronal subgroups when function is concerned. The ideal local anesthetic would only block sensory impulses, or even only painful impulses. In the search for that drug, several research avenues have been followed. First, efforts have been undertaken to extend duration of local anesthetics, by additives or extended-release formulation. Second, blockade of specific pain fibers has been attempted by targeting permanently charged anesthetics specifically into nociceptors. Third, blockade of specific isoforms using antibodies, and adaptation of naturally occurring neurotoxins has shown promise. Lastly, combination of local anesthetics with other analgesics may improve their duration of action.

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Sleep among Youth with Severely Disabling Chronic Pain: Before, during, and after Inpatient Intensive Interdisciplinary Pain Treatment.

Poor sleep is commonly reported in pediatric chronic pain. There are signals that intensive interdisciplinary pain treatments (IIPT) may inadvertently improve objective sleep, but this claim cannot be substantiated without baseline sleep data prior to IIPT. This study followed the objective sleep/wake patterns (e.g., duration, quality, timing, consistency) of pediatric patients with severely functionally disabling chronic pain before, during, and after inpatient IIPT (the Functional Independence Restoration Program-"FIRST Program"), alongside a similarly-disabled chronic pain Comparison Group. The final sample included = 10 FIRST Patients and = 9 Comparison Group patients. At baseline, the whole sample showed healthy sleep duration (~9 h), average sleep efficiency <90%, late sleep onset and offset (mean = 11:56 p.m.-8:50 a.m.), and highly inconsistent sleep schedules night to night. During IIPT, FIRST Patients maintained healthy sleep durations, moved sleep schedules 2 h earlier, and decreased timing and duration variability by >60 min while the Comparison Group maintained similar sleep to baseline. At follow up (1-2 months later), FIRST Patients' sleep schedules shifted later but were still less variable than at baseline. Results point to the malleability of sleep/wake patterns within treatment contexts with strict environmental control but suggest that these gains may be difficult for youth with chronic pain to maintain in the home environment.

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Headache characteristics and burden from chronic migraine with medication overuse headache: Cross-sectional observations from the Medication Overuse Treatment Strategy trial.

To describe headache characteristics, medication use, disability, and quality of life in a large patient cohort from the United States who have chronic migraine (CM) and medication overuse headache (MOH).

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