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Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.
Learn More >This paper presents and discusses recent evidence on the pathophysiological mechanisms of pain. The role of tapentadol-an opioid characterized by an innovative mechanism of action (i.e., µ-opioid receptor [MOR] agonism and inhibition of noradrenaline [NA] reuptake [NRI])-in the modulation of pain, and the most recent pharmacological evidence on this molecule (e.g., the µ-load concept) are also presented and commented upon. Narrative review. Solid evidence has highlighted the importance of central sensitization in the transition from acute to chronic pain. In particular, the noradrenergic system holds a major role in limiting central sensitization and the progression to chronic pain. Therefore, pharmacological modulation of the noradrenergic system appears to be a well-grounded strategy for the control of chronic pain. Tapentadol is characterized by a to-date-unique mechanism of action, since it acts both as a MOR agonist and as an inhibitor of NA reuptake. The synergistic interaction of these two mechanisms allows a strong analgesic effect by acting on both ascending and descending pathways. Of note, the reduced µ-load of tapentadol limits the risk of opioid-related adverse events, such as gastrointestinal disturbances and respiratory depression. Moreover, the NA component becomes predominant, at least, in some types of pain, with consequent specific clinical efficacy in the treatment of neuropathic and chronic pain. According to these characteristics, tapentadol appears suitable in the treatment of severe uncontrolled chronic pain characterized by both a nociceptive and a neuropathic component, such as osteoarthritis or back pain.
Learn More >Neuropathic pain severely impairs rehabilitation and quality of life after spinal cord injury (SCI). The sphingosine-1-phosphate receptor agonist FTY720 plays an important protective role in neuronal injury. This study aims to examine the effects of FTY720 in a rat acute SCI model, focusing on neuropathic pain. Female rats with SCI induced by 1-minute clip compression were administered vehicle or 1.5 mg/kg of FTY720 24 hours after the injury. Using the mechanical nociceptive threshold test, we monitored neuropathic pain and performed histological analysis of the pain pathway, including the opioid receptor (MOR), hydroxytryptamine transporter (HTT), and calcitonin gene-related peptide (CGRP). The motor score, SCI lesion volume, residual motor axons, inflammatory response, glial scar, and microvascular endothelial dysfunction were also compared between the two groups. FTY720 treatment resulted in significant attenuation of post-traumatic neuropathic pain. It also decreased systemic and local inflammation, thereby reducing the damaged areas and astrogliosis and resulting in motor functional recovery. While there was no difference in the CGRP expression between the two groups, FTY720 significantly preserved the MOR in both the caudal and rostral areas of the spinal dorsal horn. While HTT was preserved in the FTY720 group, it was significantly increased in the rostral side and decreased in the caudal side of the injury in the vehicle group. These results suggest that FTY720 ameliorates post-traumatic allodynia through regulation of neuro-inflammation, maintenance of the blood brain barrier, and inhibition of glial scar formation, thereby preserving the connectivity of the descending inhibitory pathway and reducing neuropathic pain.
Learn More >To evaluate the efficacy and safety of eptinezumab, a humanized anti-calcitonin gene-related peptide monoclonal antibody, in the preventive treatment of chronic migraine (CM).
Learn More >Indoleamine 2, 3-dioxygenase 1 (IDO1) has been linked to neuropathic pain and IDO1 inhibitors have been shown to reduce pain in animals. Some studies have indicated that IDO1 expression increased after neuropathic pain in hippocampus and spinal cord, whether these changes existing in anterior cingulate cortex (ACC) and amygdala remains obscure and how IDO1 inhibition leads to analgesia is largely unknown. Here, we evaluated the antinociceptive effect of PCC0208009, an indirect IDO1 inhibitor, on neuropathic pain and examined the related neurobiological mechanisms.
Learn More >Cluster headache is a neurological disorder that patients consider the most severe pain they experience. Recognizing new treatments provides opportunities to advance current management.
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