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Opioid Prescriptions in Chronic Pain Rehabilitation. A Prospective Study on the Prevalence and Association between Individual Patient Characteristics and Opioids.

While against recommendations, long-term opioid therapy (LTOT) for chronic pain is common. This study aimed to describe the prevalence of opioid prescriptions and to study the association of patient characteristics (demographics, pain characteristics, anxiety, depressive symptoms and pain coping) with future LTOT. The sample included = 1334 chronic musculoskeletal pain patients, aged 18-65, who were assessed for Interdisciplinary Multimodal Pain Rehabilitation (IMMR) in Swedish specialist rehabilitation. Prescriptions were tracked across a two-year target period after assessment. In total, 9100 opioid prescriptions were prescribed to 55% of the sample (M = 6, IQR = 14). Prediction of LTOT was analyzed separately for those who did (24%) and did not (76%) receive IMMR. The odds of receiving opioids was similar for these subsamples, after controlling for differences in baseline characteristics. In both samples, there were significant associations between patient characteristics and future opioid prescriptions. Dysfunctional pain coping was a unique predictor of LTOT in those who received IMMR while pain intensity and depressive symptoms were unique predictors in those who did not receive IMMR. The results underscore that opioid treatment is common among patients in chronic pain rehabilitation and relates to pain and psychological factors. Understanding in detail why these factors relate to opioid prescription patterns is an important future study area as it is a prerequisite for better management and fundamental for preventing overuse.

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A novel computational technique for the quantification of temporal summation in healthy individuals.

The pathophysiology of chronic musculoskeletal pain is linked to the neurophysiologic condition known as central sensitization. Developing reliable, sensitive and clinically feasible techniques for quantifying central sensitization is a timely priority for advancing the field of chronic pain diagnosis and management.

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Validating the revised Symptom Impact Questionnaire with a proposed fibromyalgia phenotype using experimentally-induced pain and patient self-reports.

The Symptom Impact Questionnaire (SIQR), now used for over a decade, has strong psychometric properties based on patients' subjective questionnaire data and correlations with other general measures of severity. However, the construct validity of the SIQR in assessing the central features of fibromyalgia (FM) has not been tested specifically with more objective measures. This study examined the construct validity of the SIQR using clinical examination of prominent features of FM, as well as patient questionnaire data.

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Effect of preoperative cannabis use on perioperative outcomes: a retrospective cohort study.

The reported use of cannabis within surgical population is increasing. Cannabis use is potentially associated with increased harms and varied effects on pain control. These have important implications to perioperative care.

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Oxytocin receptor activation rescues opioid-induced respiratory depression by systemic fentanyl in the rat.

Opioid overdose intervention by naloxone, a high affinity receptor antagonist, reverses opioid-induced respiratory depression (OIRD) and analgesia by displacing opioids. Systemic naloxone stimulates release of the hypothalamic neuropeptide oxytocin, which has analgesic properties and participates in cardiorespiratory homeostasis. To test the hypothesis that oxytocin can reverse OIRD, we assessed the rescue potential of graded doses (0, 0.1, 2, 5, 10, 50 nmol/kg, i.v) of oxytocin to counter fentanyl (60 nmol/kg, i.v.)-induced depression of neural inspiration indexed by recording phrenic nerve activity (PNA) in anesthetized (urethane/α-chloralose), vagotomized, and artificially ventilated rats. Oxytocin dose-dependently rescued fentanyl OIRD by almost immediately reversing PNA burst arrest (=0.0057) and restoring baseline burst frequency (=0.0016) and amplitude (=0.0025) at low, but not high doses, resulting in inverted bell-shaped dose-response curves. Oxytocin receptor antagonism (40 nmol/kg, i.v.) prevented oxytocin reversal of OIRD (Arrest: =0.0066, Frequency: =0.0207, Amplitude: =0.0022). Vasopressin 1A receptor (V1aR) antagonism restored high-dose oxytocin efficacy to rescue OIRD (=0.0170 – <0.0001), resulting in classic sigmoidal dose-response curves, and prevented (=0.0135) transient hypertension from V1aR cross-activation (=0.0275). Alone, vasopressin (5 nmol/kg, i.v.) failed to reverse fentanyl respiratory arrest (=0.6184). The non-peptide oxytocin receptor agonist WAY-267464 (75 nmol/kg, i.v.), which has V1aR antagonist properties, quickly reversed fentanyl OIRD (<0.0001), with rapid recovery of PNA frequency (=0.0011) and amplitude (=0.0044) without adverse hemodynamic consequences (=0.9991). Findings indicate that peptide and non-peptide agonist activation of oxytocin receptors without V1aR cross-activation rescues fentanyl OIRD. Oxytocin receptor agonists could be lifesaving resuscitation agents that enhance rather than interrupt opioid analgesia. Oxytocin receptor activation produces analgesia. Here, we demonstrate that activation by the FDA-approved agonist oxytocin and the non-peptide partial agonist WAY-267464 can each reverse fentanyl cardiorespiratory depression. Selective targeting of oxytocin receptors for resuscitation from opioid overdose, alone or in combination with an opioid antagonist, could eliminate or attenuate negative side effects associated with traditional opioid receptor antagonism.

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Guidelines of the International Headache Society for clinical trials with neuromodulation devices for the treatment of migraine.

Although the European Medicines Agency and the US Food and Drug Administration have cleared several devices that use neuromodulation to provide clinical benefits in the acute or preventive treatment of migraine, the Clinical Trials Committee of the International Headache Society has not developed guidelines specifically for clinical trials of neuromodulation devices. In recognition of the distinct needs and challenges associated with their assessment in controlled trials, the Committee provides these recommendations for optimizing the design and conduct of controlled trials of neuromodulation devices for the acute and/or preventive treatment of migraine.

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Photophobia in migraine: A symptom cluster?

Photophobia is one of the most common symptoms in migraine, and the underlying mechanism is uncertain. The discovery of the intrinsically-photosensitive retinal ganglion cells which signal the intensity of light on the retina has led to discussion of their role in the pathogenesis of photophobia. In the current review, we discuss the relationship between pain and discomfort leading to light aversion (traditional photophobia) and discomfort from flicker, patterns, and colour that are also common in migraine and cannot be explained solely by the activity of intrinsically-photosensitive retinal ganglion cells. We argue that, at least in migraine, a cortical mechanism provides a parsimonious explanation for discomfort from all forms of visual stimulation, and that the traditional definition of photophobia as pain in response to light may be too restrictive. Future investigation that directly compares the retinal and cortical contributions to photophobia in migraine with that in other conditions may offer better specificity in identifying biomarkers and possible mechanisms to target for treatment.

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Fremanezumab for the Preventive Treatment of Migraine: Subgroup Analysis by Number of Prior Preventive Treatments with Inadequate Response.

To evaluate the efficacy of monthly or quarterly fremanezumab in patients with chronic migraine or episodic migraine and documented inadequate response to 2, 3, or 4 classes of prior migraine preventive medications.

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Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker.

Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW-031, a novel more potent cationic sodium channel inhibitor, test whether its application alone can inhibit pain associated with tissue inflammation, and whether this strategy can also inhibit cough.

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Evaluation of tradipitant, a selective NK1 antagonist, on response to oxycodone in humans.

Preclinical studies demonstrate that the NK1 receptor is involved in opioid reinforcement and withdrawal expression. Few studies have examined the impact of treatment with NK1 antagonists on opioid response in humans.

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