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A pilot exploratory study comparing the King-Devick test (KDT) during and between migraine attacks.

The King-Devick test is a timed rapid number naming task that involves complex cerebral functions. The objective of this pilot exploratory study is to determine whether there is a difference in the King-Devick test during a migraine attack compared to the interictal phase.

New frontiers in probing the dynamics of purinergic transmitters in vivo.

Purinergic transmitters such as adenosine, ADP, ATP, UTP, and UDP-glucose play important roles in a wide range of physiological processes, including the sleep-wake cycle, learning and memory, cardiovascular function, and the immune response. Moreover, impaired purinergic signaling has been implicated in various pathological conditions such as pain, migraine, epilepsy, and drug addiction. Examining the function of purinergic transmission in both health and disease requires direct, sensitive, non-invasive tools for monitoring structurally similar purinergic transmitters; ideally, these tools should have high spatial and temporal resolution in in vivo applications. Here, we review the recent progress with respect to the development and application of new methods for detecting purinergic transmitters, focusing on optical tools; in addition, we provide discussion regarding future perspectives.

Long-term opioid therapy definitions and predictors: A systematic review.

This review sought to (a) describe definitions of long-term opioid therapy (LTOT) outcome measures, and (b) identify the predictors associated with the transition from short-term opioid use to LTOT for opioid-naïve individuals.

The application of psychologically informed practice: observations of experienced physiotherapists working with people with chronic pain.

Psychologically informed practice (PIP) is advocated for physiotherapists to help people with chronic pain. There is little research observing how PIP is delivered in clinical practice. This study describes behaviours and techniques used by experienced physiotherapists working with groups of people with chronic pain.

Itch and mental health in dermatological patients across Europe: a cross sectional study in 13 countries.

Itch is a highly prevalent and multi-dimensional symptom. We aimed to analyze the association between itch and mental health in dermatological patients. This multi-center study is observational cross-sectional conducted in dermatological clinics across 13 European countries. A total of 3530 patients and 1094 healthy controls were included. Patients were examined clinically. Outcome measures were itch (presence, chronicity and intensity), the Hospital Anxiety and Depression Scale, EQ5D-VAS, sociodemographics, suicidal ideation, stress (negative life events and economic difficulties). Ethical approval was obtained. Results showed significant association between the presence of itch in patients and clinical depression, suicidal ideation and economic difficulties (odds ratios respectively OR 1.53 (95% CI 1.15 to 2.02), OR 1.27 (95% CI 1.01 to 1.60), OR 1.24 (95% CI 1.10 to 1.50). The mean score of reported generic health status assessed by the EQ5D-VAS was 65.9 (SD=20.1) in patients with itch, compared to 74.7 (SD= 18.0) in patients without itch, p value < .001 and 74.9 (SD= 15.7) in controls with itch compared to 82.9 (SD= 15.6) in controls without itch, p value <.001. Itch contributes substantially to the psychological disease burden in dermatological patients and the management of patients should include access to multidisciplinary care.

Pharmacologic characterization of JNJ-42226314, [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a reversible, selective and potent monoacylglycerol lipase inhibitor.

The serine hydrolase monoacylglycerol lipase (MAGL) is the rate-limiting enzyme responsible for the degradation of the endocannabinoid 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. Inhibition of 2-AG degradation leads to elevation of 2-AG, the most abundant endogenous agonist of the cannabinoid receptors CB1 and CB2. Activation of these receptors have demonstrated beneficial effects on mood, appetite, pain and inflammation. Therefore, MAGL inhibitors have the potential to produce therapeutic effects in a vast array of complex human diseases. The present report describes the pharmacologic characterization of JNJ-42226314, [1-(4-fluorophenyl)indol-5-yl]-[3-[4-(thiazole-2-carbonyl)piperazin-1-yl]azetidin-1-yl]methanone, a reversible and highly selective MAGL inhibitor. JNJ-42226314 inhibits MAGL in a competitive mode with respect to the 2-AG substrate. In rodent brain, the compound time- and dose-dependently bound to MAGL, indirectly led to CB1 occupancy by raising 2-AG levels and raised norepinephrine levels in cortex. In vivo, the compound exhibited antinociceptive efficacy in both the rat complete Freund's adjuvant (CFA)-induced radiant heat hypersensitivity and chronic constriction injury (CCI)-induced cold hypersensitivity models of inflammatory and neuropathic pain, respectively. Although 30 mg/kg induced hippocampal synaptic depression, altered sleep onset and decreased EEG gamma power, 3 mg/kg still provided approximately 80% enzyme occupancy, significantly increased 2-AG and norepinephrine levels and produced neuropathic antinociception without synaptic depression or decreased gamma power. Thus, it is anticipated that the profile exhibited by this compound will allow for precise modulation of 2-AG levels in vivo, supporting potential therapeutic application in several CNS disorders. SIGNIFICANCE STATEMENT: Potentiation of endocannabinoid signaling activity via inhibition of the serine hydrolase monoacylglycerol lipase (MAGL) is an appealing strategy in the development of treatments for several disorders, including ones related to mood, pain and inflammation. JNJ-42226314 is presented in this report to be a novel, potent, selective and reversible non-covalent MAGL inhibitor that demonstrates dose-dependent enhancement of the major endocannabinoid 2-arachidonoylglycerol as well as efficacy in models of neuropathic and inflammatory pain.

Reducing the use of opioids by patients with chronic pain: an effectiveness study with long-term follow-up.

This paper addresses the problem of long-term opioid use by chronic pain patients. The study involved a secondary analysis of unanalysed data from a published study of two versions of CBT-based interdisciplinary treatment for chronic pain. In this paper we examined whether the use of opioids by 140 chronic pain patients could be ceased sustainably over 12-months following participation in the comprehensive interdisciplinary pain management program aimed at enhancing pain self-management. On admission to the treatment there were no significant differences between those patients taking or not taking opioids on usual pain, pain interference in daily activities, pain-related disability, depression severity, as well as in pain cognitions. Following the treatment the use of opioids was significantly reduced, both in numbers taking any and in mean doses, and these gains were maintained over the 12-month follow-up. Finally, cessation of opioids during treatment was associated with more substantial and consistent improvements in usual pain, depression severity, pain interference, pain-related disability, and pain cognitions, relative to those who reduced their opioids but did not cease them. These findings support the idea of using training in pain self-management strategies as a viable alternative to long-term opioid use by patients with chronic pain.

Sex differences in the relationship between anxiety sensitivity and opioid misuse among adults with chronic pain.

The opioid epidemic is a significant public health concern linked to chronic pain. Despite efforts to change opioid prescribing practices for chronic pain, opioid-involved overdoses remain at an all-time high. Research focused on identifying individual difference factors for problematic opioid misuse in the context of chronic pain have identified certain psychological variables that may confer heightened risk for opioid-related problems. Anxiety sensitivity, or fear of anxiety-related physical sensations, has been linked to opioid-related problems among adults with chronic pain. Yet, it is possible that these relations may not be distributed equally in society, and sex differences may be one avenue by which these relations differ. Therefore, the current study examined the moderating role of sex on the relation between anxiety sensitivity, current opioid misuse, and severity of opioid dependence among 428 adults (74.9% female, M = 38.28 years, SD = 11.06) with chronic pain. Results indicated that the relation between anxiety sensitivity and current opioid misuse (ΔR = 0.005, B = 0.12, SE = 0.06, p = 0.04), and opioid dependence (ΔR = 0.01, B = 0.04, SE = 0.02, p = 0.007) was stronger for males compared to females. These results suggest that anxiety sensitivity may be associated with opioid-related problems to a greater extent for males than females. Continued research is needed to examine how these sex differences may impact clinical treatment for opioid-related problems.

Nonpharmacological Treatment of Army Service Members with Chronic Pain Is Associated with Fewer Adverse Outcomes After Transition to the Veterans Health Administration.

Potential protective effects of nonpharmacological treatments (NPT) against long-term pain-related adverse outcomes have not been examined.

TRESK background K channel deletion selectively uncovers enhanced mechanical and cold sensitivity.

TRESK background K channel is expressed in sensory neurons and acts as a brake to reduce neuronal activation. Deletion of the channel enhances the excitability of nociceptors Skin nociceptive C-fibers show an enhanced activation by cold and mechanical stimulation in TRESK KO animals. Channel deletion selectively enhances mechanical and cold sensitivity in mice, without altering sensitivity to heat. These results indicate that the channel regulates the excitability of specific neuronal subpopulations involved in mechanosensitivity and cold-sensing.

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