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An increase in opioid prescription has been observed in the Netherlands. It is vital to understand this increase and to identify risk factors for opioid prescription to ensure that health interventions remain appropriately targeted.
Learn More >The present study investigated the role of the amygdala NMDA receptors/NOS pathway in morphine-induced anti-allodynia. Concurrently with the bilateral cannulation of the central amygdala (CeA), chronic constriction of the sciatic nerve was performed on male Wistar rats. Morphine (3-5 mg/kg) was intraperitoneally administered to induce anti-allodynia. When D-AP5, a selective NMDA receptor antagonist, (0.05-0.1 µg/rat) or L-NAME, the NO synthase inhibitor, (0.1-0.5 µg/rat) were microinjected into the CeA, the higher doses potentiated an ineffective dose of morphine (3 mg/kg). Microinjection of the same doses of D-AP5 and L-NAME without morphine had no effect. Co-microinjection of the ineffective doses of L-NAME (0.1 µg/rat) and D-AP5 (0.05 µg/rat) with a 5-min interval, enhanced the anti-allodynic effect of morphine (3 mg/kg). Western blot analysis was employed to evaluate the levels of cAMP-response element-binding protein (CREB) and phosphorylated CREB (pCREB) in the amygdala tissues. Our results showed that neuropathic pain increased the pCREB/CREB ratio in the amygdala, while this ratio was decreased following morphine-induced anti-allodynia. The potentiative effect of the co-administration of D-AP5/L-NAME on an ineffective dose of morphine also decreased the amygdala pCREB/CREB levels. Therefore, it seems that the amygdala pCREB/CREB signaling pathway plays a critical role in processing neuropathic pain. Moreover, the glutamate NMDA receptors and NO system in the amygdala may be involved in morphine-induced anti-allodynia. PERSPECTIVE: Neuropathic pain is hard to treat and the exact mechanisms are still unknown. This article suggests the importance of the amygdala glutamatergic and nitric oxide systems in morphine-induced anti-allodynia. The findings might be used in clinical studies to reach a better understanding of neuropathic pain mechanisms and treatment.
Learn More >Neuropathic pain, which presents abnormal pain manifestations including allodynia and hyperalgesia, is associated with central sensitization involving N-methyl-D-aspartate receptorsIn the freeze-injury hyperalgesia model, a cold burn leads to development of both primary hyperalgesia and secondary hyperalgesia, which develops away from the site of injury without apparent tissue modification, and is associated with central sensitization and activation of N-methyl-D-aspartate receptors in the spinal cordDextromethorphan, which is an N-methyl-D-aspartate receptor antagonist, is antihyperalgesic in preclinical pain models WHAT THIS ARTICLE TELLS US THAT IS NEW: Using the freeze-injury pain model in a randomized, double-blind, placebo-controlled crossover trial of 30-mg doses of oral dextromethorphan in 20 male volunteers, dextromethorphan was antihyperalgesic and reversed peripheral and central neuronal sensitizationBecause dextromethorphan had no intrinsic antinociceptive effect in acute pain on healthy skin, N-methyl-D-aspartate receptors may need to be sensitized by pain for dextromethorphan to be effective BACKGROUND:: Central pain sensitization is often refractory to drug treatment. Dextromethorphan, an N-methyl-D-aspartate receptor antagonist, is antihyperalgesic in preclinical pain models. The hypothesis is that dextromethorphan is also antihyperalgesic in humans.
Learn More >The monosodium iodoacetate (MIA)-induced joint degeneration in rats is the most used animal model to screen analgesic drugs to alleviate osteoarthritis (OA) pain. This study aimed to evaluate the analgesic efficacy of pregabalin (PGB) in an MIA-induced OA model in rodents by using functional and neuroproteomic pain assessment methods. Treatment group included PGB in curative intent over 9 days compared to gold standard therapy (positive controls) and placebo (negative control). Functional assessments of pain (quantitative sensory testing and operant test) were performed concomitantly with spinal neuropeptides quantification. At day 21 post-OA induction, PGB in MIA rats reduced tactile allodynia (P = 0.028) and improved the place escape/avoidance behavior (P = 0.04) compared to values recorded at last time-point before initiating analgesic therapy. All spinal neuropeptide concentrations, such as substance P, calcitonin gene-related peptide, bradykinin and somatostatin, came back to normal (non affected) rat values, compared to their increase observed in MIA rats receiving the placebo (P < 0.0001). Initiated 13 days after chemical OA induction, repeated medication with PGB provided analgesia according to quantitative sensory testing, operant test and targeted neuropeptides pain assessment methods. This report highlights the interest of using reliable and sensitive methods like targeted neuropeptide quantification to detect the analgesic effects of a test article with concomitant functional assessments of pain when studying OA pain components. This article is protected by copyright. All rights reserved.
Learn More >As new migraine prevention treatments are developed, the onset of a preventive effect, how long it is maintained and whether patients initially non-responsive develop clinically meaningful responses with continued treatment can be assessed.
Learn More >: Chronic pain conditions of malignant and non-malignant etiology afflict a large group of the population and pose a vast economic burden on society. Intrathecal drug therapy is a viable treatment option in such patients who have failed conservative medical measures and less invasive pain management procedures. However, the clinical growth of intrathecal therapyin managing intractable chronic pain conditions continues to face many challenges and is likely underutilized secondary to its high-complexity and lack of understanding. : This review will briefly discuss the history of intrathecal drug delivery systems (IDDS), cerebrospinal fluid (CSF) flow dynamics, types of IDDS, indications and patient profile suitable for this therapy, and risks and complications related to IDDS. We will also discuss challenges faced by physicians utilizing this therapy and the future changes that are needed for making this treatment modality more efficacious. : IDDS offer an effective therapy for pain control in patients suffering from chronic intractable pain conditions. These devices provide a safer alternative to oral opioid medications with reduced systemic side effects. Adherence to best practices and continued clinical and basic science research is important to ensure continuing success of this therapy.
Learn More >This study investigated the analgesic effects of two doses (15 and 65 mg) of PF-06372865, a novel α2/α3/α5 gamma-aminobutyric acid A (GABA) subunit selective partial positive allosteric modulator (PAM), compared with placebo and pregabalin (300 mg) as a positive control.
Learn More >This paper reviews placebo-controlled randomized double-blind studies with erenumab for the prevention of migraine. Erenumab is a fully human monoclonal antibody (mAb), which specifically blocks the calcitonin gene-related peptide (GGRP) receptor. Areas covered: This manuscript was based on articles written in English located on PubMed found using the following search terms:episodic & chronic migraine, migraine prophylaxis & prevention, CGRP, CGRP receptor, CGRP receptor antagonist, erenumab, treatment failures, trigeminal nerve. Expert commentary: The primary endpoints in Phase II and III preventative episodic migraine trials have been reached successfully, and so have multiple secondary endpoints. Monthly subcutaneous injections of either erenumab 70 or 140 mg reduced mean monthly migraine days (MMDs) after a 3 and 6 months significantly greater than placebo when compared to baseline values with an onset of action within the first week. About 50% of subjects have a at least 50% reduction of MMDs. Several patient-reported outcome measures demonstrate improved quality of life with erenumab. This antibody shows efficacy in a prior treatment failure population. The tolerability of erenumab is good, which is reflected by low dropout rates in all erenumab clinical trials. Within the first year of treatment, no specific group or type class of adverse events were observed.
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