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Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD).
Learn More >In response to the national opioid public health crisis, there is an urgent need to develop nonopioid solutions for effective pain management. Neurosteroids are endogenous molecules with pleotropic actions that show promise for safe and effective treatment of chronic low back pain.
Learn More >A comprehensive overview and safety evaluation of fremanezumab as a preventive therapy for migraine.
: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP mAb), is a migraine-specific treatment for migraine prevention.: This review will briefly discuss other available and emerging CGRP mAbs and the neurophysiology of fremanezumab. The review will focus on phase III trials of the efficacy of fremanezumab for episodic and chronic trials, and a recent pooled safety and tolerability analysis of its use.: Continued efficacy and safety data collection will help guide long-term risk and efficacy counseling in the general population.
Learn More >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.
Learn More >Patients who have limb amputation are at risk of chronic pain, including phantom limb pain, that can be challenging to treat. The aim of this study was to describe the incidence of preoperative opioid usage and the incidence and risk factors for new persistent postoperative opioid usage in opioid-naïve patients after limb amputation.
Learn More >Opioids have been increasingly prescribed for chronic non-cancer pain (CNCP). An association between long-term opioid treatment (L-TOT) of CNCP patients and suppression of both the innate and the adaptive immune system has been proposed. This systematic review aims at investigating the effects of L-TOT on the immune system in CNCP patients.
Learn More >The popular herbal medicine, St. John's wort, is a potent inducer of several cytochrome P450 enzymes, including CYP3A4, which plays a role in the metabolism of fentanyl. St. John's wort may also influence the expression of P-glycoprotein, which can alter the movement of drugs across the blood-brain barrier.
Learn More >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.
Learn More >Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low-dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, six and 12 months after major lower back surgery.
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