Mol Pain
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Polysorbate 80 is a non-ionic detergent derived from polyethoxylated sorbitan and oleic acid. It is widely used in pharmaceuticals, foods, and cosmetics as an emulsifier. Nav1.7 is a peripheral sodium channel that is highly expressed in sympathetic and sensory neurons, and it plays a critical role in determining the threshold of action potentials (APs). ⋯ Our results indicate that polysorbate 80 inhibits Nav1.7 current in concentration-, state-, and use-dependent manners when used even below commercial concentrations. This suggests that polysorbate 80 may be helpful in pain medicine as an excipient. In addition, in vitro experiments using polysorbate 80 with neurons should be conducted with caution.
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Acupuncture, as a traditional treatment, has been extensively used in China for thousands of years. According to the World Health Organization (WHO), acupuncture is recommended for the treatment of 77 diseases. And 16 of these diseases are related to inflammatory pain. ⋯ We elucidated on its mechanisms of action on inflammatory pain from two levels: peripheral and central. It includes the mechanisms of acupuncture in the periphery (immune cells and neurons, purinergic pathway, nociceptive ion channel, cannabinoid receptor and endogenous opioid peptide system) and central nervous system (TPRV1, glutamate and its receptors, glial cells, GABAergic interneurons and signaling molecules). In this review, we collected relevant recent studies to systematically explain the mechanisms of acupuncture in treating inflammatory pain, with a view to providing direction for future applications of acupuncture in inflammatory pain and promoting clinical development.
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The role of Aβ-afferents in somatosensory function is often oversimplified as low threshold mechanoreceptors (LTMRs) with large omission of Aβ-afferent involvement in nociception. Recently, we have characterized Aβ-afferent neurons which have large diameter somas in the trigeminal ganglion (TG) and classified them into non-nociceptive and nociceptive-like TG afferent neurons based on their electrophysiological properties. Here, we extend our previous observations to further characterize electrophysiological properties of trigeminal Aβ-afferent neurons and investigate their mechanical and chemical sensitivity by patch-clamp recordings from large-diameter TG neurons in ex vivo TG preparations of adult male and female rats. ⋯ Type I, IIa, and IIb neurons were mostly mechanically sensitive, displaying robust and rapidly adapting mechanically activated current (IMA) in response to membrane displacement, while IIIa and IIIb, conversely, were almost all mechanically insensitive. Interestingly, mechanical insensitivity coincided with increased sensitivity to 5-HT and ACh. Together, type I, IIa and IIb display features of LTMR Aβ-afferent neurons while type IIIa and type IIIb show properties of nociceptive Aβ-afferent neurons.
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Sleep deprivation can trigger migraine, and migraineurs often choose to sleep to relieve headaches during acute migraine. This study aimed to explore the effect of acute sleep deprivation on hyperalgesia induced by nitroglycerin in mice. In part one, after either 6-h sleep deprivation or 6-h normal sleep, mice were intraperitoneally injected with nitroglycerin or saline. ⋯ When intraperitoneal injection was given first, the mechanical pain threshold of the hind paw was significantly lower in the group that received nitroglycerin with 6-h sleep deprivation than in the other groups. Compared to the saline injection, one-time nitroglycerin injection would result in a significant increase in sleep latency and decrease in sleep duration for the normal mice. Acute sleep deprivation significantly aggravated the hyperalgesia induced by nitroglycerin in mice, which highlights the importance of sleep disorders for migraine.
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Background: Migraine is a common type of primary headache with disabling brain dysfunction. It has been found that pituitary adenylate cyclase activating polypeptide (PACAP) is involved in the pathogenesis of migraine, however, the role of PACAP and its receptors in chronic migraine remains unclear. Therefore, the present study aimed to explore the changes of PACAP and its receptors in different duration after recurrent dural inflammation soup stimulations and to investigate the co-expression between PACAP and calcitonin gene-related peptide (CGRP). ⋯ While the co-expression between PACAP and CGRP reached the peak in IS-7 group after repetitive IS stimulation, and then decreased. Conclusions: This study demonstrated that repetitive chemical stimulations induced a gradual decrease of PACAP in the TNC, while the PACAP and PAC1 receptor expression in TG showed dynamical changes of increasing first and then decreasing after repeated IS administration. These results suggested exhaustion of PACAP could be involved in the duration of chronic migraine and implied PACAP may contribute to the pathology of migraine through the PAC1 receptor, which was associated with CGRP.