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The prevalence of hypnic headache in Iceland.

To determine the prevalence of hypnic headache.

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Behavioral activation and behavioral inhibition: An examination of function in chronic pain.

The objective of the study was to examine the BIS-BAS model of chronic pain. This model posits that 2 neurophysiological systems-the behavioral inhibition system (BIS) sensitized to and activated by punishment cues and the behavioral activation system (BAS) sensitized to and activated by reward cues-make independent and concurrent contributions to 2 domains of pain-related function: pain interference and positive function despite pain. The study additionally hypothesized that BIS and BAS sensitivity would have different associations with these 2 different aspects of pain-related function. BIS activation would be more strongly correlated with pain interference and BAS would be more strongly correlated with positive function despite pain. Research Method/Design: This was a cohort study consisting of the baseline assessments of 328 veterans enrolled in a large clinical trial examining 3 psychosocial interventions for chronic pain.

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Pain and Psychological Outcomes Among Iraq and Afghanistan Veterans with Chronic Pain and PTSD: ESCAPE Trial Longitudinal Results.

To compare pain and psychological outcomes in veterans with chronic musculoskeletal pain and comorbid post-traumatic stress disorder (PTSD) or pain alone and to determine if veterans with comorbidity respond differently to a stepped-care intervention than those with pain alone.

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Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.

To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.

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Parent Responses to Their Child’s Pain: Systematic Review and Meta-Analysis of Measures.

Parent responses can have a major impact on their child's pain. The purpose of this systematic review is to (a) identify and describe measures assessing pain-related cognitive, affective, and behavioral responses in parents of children with chronic pain and (b) meta-analyze reported correlations between parent constructs and child outcomes (i.e., pain intensity, functional disability, and school functioning). Prospero protocol registration ID: CRD42019125496.

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Promoting an interprofessional approach to chronic pain management in primary care using Project ECHO.

Chronic pain is a complex multidimensional condition that requires management with multiple professions' expertise. Healthcare training programs tend to adhere to curricula within their own profession with very few interactions with other groups. Project ECHO (Extension for Community Healthcare Outcomes) Chronic Pain and Opioid Stewardship is a model for interprofessional education, using tele-mentoring, case-base discussions and clinically focused presentations. The goal is to improve competency and confidence in managing complex cases in primary care. This qualitative study engaged twenty healthcare practitioners from multiple professions who had participated in ECHO in focus group discussions about managing patients with chronic pain, about their reasons for and the effect of participating in Project ECHO Ontario Chronic Pain/Opioid Stewardship, and about their perspectives on interprofessional care. The results show that participating in ECHO resulted in personal and professional benefit, and increased understanding about their own roles and limitations, as well as other healthcare professionals' roles. The participants described changes in their attitudes toward patients with chronic pain, and their colleagues from other professions. Non-physician participants were more likely to approach physicians to discuss their assessment and diagnosis as well as prescriptions. The interprofessional nature of the program was seen as positive and contributed to perceived changes in practice collaboration. These results show that healthcare professionals from multiple professions expressed mainly positive views of ECHO's emphasis on interprofessional care, with different professions appreciating different aspects of that approach.

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Structural abnormalities in the temporalis musculo-aponeurotic complex in chronic muscular temporomandibular disorders.

Some forms of chronic pain are thought to be driven and maintained by nociceptive input, which can drive plasticity within nociceptive pathways. We have previously identified abnormalities along the entire nociceptive pathway in chronic myalgic temporomandibular disorders (mTMD), including the trigeminal nerves, brainstem pathways, and in the thalamus and somatosensory cortex. These data suggest that there is a peripheral nociceptive drive in mTMD, but the source of this nociceptive activity remains unknown. Here, our aim was to determine whether structural abnormalities exist in the muscles of mastication of patients with chronic mTMD. Specifically, we tested whether the volume of the temporalis muscle and its tendon-aponeurosis-complex (TAC, a structure that dissipates forces in a muscle) in mTMD patients differ compared to age- and sex-matched controls. To do so, we segmented these structures on T1-weighted structural MR images. We found that muscle volumes in mTMD were not different to controls. However, the mTMD group had significantly smaller volumes of the bilateral temporalis TAC, and thus a smaller TAC-to-muscle volume ratio. These findings were consistent across 2 independent cohorts of 17 mTMD patients, compared to 17 age- and sex-matched controls. We propose a model where reduced TAC-to-muscle ratio could result in a predisposition to muscle tissue injury. In sum, abnormalities of the temporalis muscles in mTMD supports our hypothesis that chronic mTMD pathophysiology may be related to peripheral nociceptive barrage originating from the muscles of mastication.

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Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Severe pain often accompanies major spine surgery. Opioids are the cornerstone of postoperative pain management but their use can be limited by numerous side effects. Several studies claim that adjuvant treatment with intravenous (IV) ketamine reduces opioid consumption and pain after back surgery. However, the exact role of ketamine for this indication is yet to be elucidated. We compared 2 different doses of S-ketamine with placebo on postoperative analgesic consumption, pain, and adverse events in adult, opioid-naïve patients after lumbar fusion surgery.

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HCN2 contributes to oxaliplatin-induced neuropathic pain by inducing spinal long-term potentiation via activation of NMDA receptor-mediated CaMKII signaling.

Our previous findings indicate that HCN2 contributes to oxaliplatin-induced neuropathic pain, but the mechanisms underlying the development of neuropathic pain are still unclear. Here, we found that the rat HCN2 levels significantly increased after high-frequency stimulation-induced long-term potentiation (LTP). Spinal local application of ZD7288 (a cyclic-nucleotide-gated-channel-specific inhibitor) prevented LTP induction after intraperitoneal injection of oxaliplatin. In addition, oxaliplatin administration induced spinal LTP via activation of the CaMKII-CREB cascade in the rat spinal dorsal horn. Moreover, we found that administration of oxaliplatin significantly increased the amplitude of excitatory postsynaptic currents and the number of action potentials, but these effects were attenuated by pretreatment with either CaMKII inhibitor KN-93 or NR2B antagonist Ro 25-6981. An increase in the phosphorylation of spinal N-methyl-d-aspartate (NMDA) receptor subunit 1 (NR1) after oxaliplatin administration was weakened by ZD7288 pretreatment. Administration of noncompetitive NMDA receptor antagonist MK-801 blocked oxaliplatin-evoked CaMKII-CREB cascade activation and prevented HCN2-mediated spinal-LTP induction in vitro and suppressed neuropathic-pain behaviors of rats. All these data suggest that HCN2 contributes to the development of neuropathic pain by inducing spinal LTP via activation of NMDA receptor-mediated CaMKII signaling.

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Replacement of current opioid drugs focusing on MOR-related strategies.

The scarcity and limited risk/benefit ratio of painkillers available on the market, in addition to the opioid crisis, warrant reflection on new innovation strategies. The pharmacopoeia of analgesics is based on products that are often old and derived from clinical empiricism, with limited efficacy or spectrum of action, or resulting in an unsatisfactory tolerability profile. Although they are reference analgesics for nociceptive pain, opioids are subject to the same criticism. The use of opium as an analgesic is historical. Morphine was synthesized at the beginning of the 19th century. The efficacy of opioids is limited in certain painful contexts and these drugs can induce potentially serious and fatal adverse effects. The current North American opioid crisis, with an ever-rising number of deaths by opioid overdose, is a tragic illustration of this. It is therefore legitimate to develop research into molecules likely to maintain or increase opioid efficacy while improving their tolerability. Several avenues are being explored including targeting of the mu opioid receptor (MOR) splice variants, developing biased agonists or targeting of other receptors such as heteromers with MOR. Ion channels acting as MOR effectors, are also targeted in order to offer compounds without MOR-dependent adverse effects. Another route is to develop opioid analgesics with peripheral action or limited central nervous system (CNS) access. Finally, endogenous opioids used as drugs or compounds that modify the metabolism of endogenous opioids (Dual ENKephalinase Inhibitors) are being developed. The aim of the present review is to present these various targets/strategies with reference to current indications for opioids, concerns about their widespread use, particularly in chronic non-cancer pains, and ways of limiting the risk of opioid abuse and misuse.

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