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To evaluate the efficacy and safety of eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of episodic migraine.
Learn More >Transient receptor potential vanilloid 1 (TRPV1) is a polymodal receptor channel, which plays an important role in pain transduction. It is important to understand the functional expression of this channel under neuropathic pain (NP) conditions. A novel method was used to investigate the dynamics of functional expression of this channel on regenerated neurons under NP conditions following trigeminal nerve injury using a combination of a permanently charged sodium channel blocker (QX-314) and a TRPV1 agonist (capsaicin; QX-CAP). The combination was originally introduced as a local anesthetic. Synchronization between the local anesthetic effect of QX-CAP and TRPV1 expression on regenerated neurons was observed following the nerve injury. QX-CAP had no local anesthetic effect under NP conditions 2 weeks after the injury when TRPV1 expression on regenerated neurons was low. However, this combination was effective under NP conditions 3 and 4 weeks following injury when TRPV1 expression in regenerated neurons was moderate to high. The current review, discusses the potential of QX-314 as a local anesthetic and a novel approach of using QX-CAP to reveal the dynamics of functional expression of TRPV1 on regenerated neurons following trigeminal nerve injury.
Learn More >To evaluate the efficacy of ubrogepant on patient-reported functional disability, satisfaction with study medication, and global impression of change.
Learn More >Conditioned pain modulation (CPM) is a task that involves measuring pain in response to a test stimulus before and during a painful conditioning stimulus (CS). The CS pain typically inhibits pain elicited by the test stimulus; thus, this task is used to assess endogenous pain inhibition. Moreover, less efficient CPM-related inhibition is associated with chronic pain risk. Pain catastrophizing is a cognitive-emotional process associated with negative pain sequelae, and some studies have found that catastrophizing reduces CPM efficiency.
Learn More >: Neuropathic pain is a chronic condition that significantly affects the quality of life of millions of people globally. Most of the pharmacologic treatments currently in use demonstrate modest efficacy and over half of all patients do not respond to medical management. Hence, there is a need for new, efficacious drugs. Evidence points toward voltage-gated sodium channels as a key target for novel analgesics.: The role of voltage-gated sodium channels in pain pathophysiology is illuminated and the preclinical and clinical data for new sodium channel blockers and toxin-derived lead compounds are examined. The expansion of approved sodium channel blockers is discussed along with the limitations of current research, trends in drug development, and the potential of personalized medicine.: The transition from preclinical to clinical studies can be difficult because of the inherent inability of animal models to express the complexities of pain states. Pain pathways are notoriously intricate and may be pharmacologically modulated at a variety of targets; it is unlikely that action at a single target could completely abolish a pain response because pain is rarely unifactorial. Combination therapy may be necessary and this could further confound the discovery of novel agents.
Learn More >The authors' previous studies have found that spinal protein kinase C γ expressing neurons are involved in the feed-forward inhibitory circuit gating mechanical allodynia in the superficial dorsal horn. The authors hypothesize that nerve injury enhances the excitability of spinal protein kinase C γ expressing interneurons due to disinhibition of the feed-forward inhibitory circuit, and enables Aβ primary inputs to activate spinal protein kinase C γ expressing interneurons.
Learn More >Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist and novel sedative drug with minimal respiratory suppression, have shown anti-nociceptive activity in various pain models by poorly understood mechanisms. Because alpha-2 adrenergic receptor is co-localized with TRPV1 polymodal nociceptive receptor in dorsal root ganglion neurons and up-regulated in neuropathic pain animal models, the analgesic activity might be mediated through inhibition of TRPV1 in the peripheral nervous system. In an effort to elucidate whether modulatory effect of dexmedetomidine on TRPV1 activity could be the potential peripheral mechanism underlying the antinociceptive effect of dexmedetomidine, intracellular calcium concentration after capsaicin application was investigated in mice dorsal root ganglion (DRG) neurons, with and without pretreatment of dexmedetomidine. Dexmedetomidine (10 μM) reduced capsaicin-induced calcium responses by 29.7 ± 7.39% (n = 34, p < 0.0001), in dose-dependent manner. Higher level of inhibition was observed with increased dose of dexmedetomidine (50 μM, 45.1 ± 8.58%, n = 15, p = 0.0002), and lower inhibition by decreased dose (1 μM, 18.8 ± 1.48%, n = 148, p = 0.004). RT-PCR analysis revealed expression of TRPV1 and alpha-2A, alpha-2B and alpha-2C subtypes of adrenergic receptor in mice DRG neurons, and immunocytochemical analysis revealed co-expression of TRPV1 and alpha-2A receptors in primary cultured DRG neurons. In summary, these results suggested the inhibition of TRPV1 expressed in the primary sensory neurons as a potential mechanism that contributes to the anti-nociceptive action of dexmedetomidine.
Learn More >Peripheral nerve injury typically leads to chronic inflammation through recruitment of immune cells, which may induce neuropathic pain. We previously reported that M1-like macrophages at sites of peripheral nerve injury induced neuropathic pain; however, the involvement of other immune cells (e.g. M2-like macrophages) in the progression of neuropathic pain remains unclear. In addition, the immune responses that occur at sites of nerve injury have not been well characterized. In this study, we show that M2-like macrophages accumulate in injured nerves to participate in the clearance of dead or dying cells (i.e., efferocytosis). Because MerTK (a receptor of dead or dying cells) levels on the surface of macrophages are limited, it seems to induce the insufficient of efferocytosis, such that the levels of dead or dying cells cannot be controlled in injured nerves. Given that efferocytosis is pivotal for resolution of inflammation, our data suggest that insufficient efferocytosis is a contributing factor in the development of chronic inflammation in injured nerves.
Learn More >The current study assessed the role of hypervigilance for bodily sensations in the back in long term low back pain (LBP) problems.
Learn More >Conditioned pain modulation (CPM) and manipulation induced analgesia (MIA) are two forms of endogenous analgesia. Many forms of analgesia can be influenced by the nature of the patient clinician interaction. The aim of this study was to evaluate the influence of an empathetic and supportive interaction on CPM and MIA in people with Lateral Epicondylalgia (LE).
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