Mol Pain
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Chronic migraine is a common chronic daily headache featured by frequent headache attacks with at least 15 headache days per month, which brings great disease burden to both the sufferers and the society. Transformed from episodic migraine, the pathophysiology of chronic migraine is not fully understood, even though several risk factors have been associated with migraine progression. ⋯ Chronic migraine is undertreated because of its poor treatment response and limited therapy options. In this article, we reviewed the latest data to outline the clinical feature, pathophysiological mechanism, and management of chronic migraine, in the expectation to provide direction for future research and finally to take good care of chronic migraine patients.
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Background Severe postoperative pain remains a clinical problem that impacts patient's rehabilitation. The present work aims to investigate the role of Toll-like receptor-4 (TLR4) activation in wounded plantar tissue and dorsal root ganglion (DRG) in the genesis of postoperative pain and its underlying mechanisms. Results Postoperative pain was induced by plantar incision in rat hind paw. ⋯ Moreover, the plantar s.c. injection of TAK-242 or PDTC inhibited the increased expressions of p-p65, tumor necrosis factor-alpha, and interleukin-1 beta not only in local wounded plantar tissue but also dramatically in ipsilateral lumbar 4-5 DRGs. Conclusion TLR4/ nuclear factor-kappa B signaling activation in local injured tissue and DRG contribute to the development of postoperative pain via regulating pro-inflammatory cytokines release. Targeting TLR4/ nuclear factor-kappa B signaling in local tissue at early stage of surgery may be an effective strategy for the treatment of postoperative pain.
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We have previously reported that histamine-induced pruritus was attenuated in toll-like receptor 4 (TLR4) knockout mice due to decreased transient receptor potential V1 (TRPV1) sensitivity. Our results implied that TLR4 potentiated TRPV1 activation in sensory neurons; however, the molecular mechanism has yet to be elucidated. In this study, we investigated the molecular mechanisms of TLR4-mediated TRPV1 potentiation using TLR4-deficient sensory neurons and a heterologous expression system. ⋯ Our data show that direct association between TRPV1 and TLR4 through the TIR domain enhances TRPV1 activity by blocking activation-induced TRPV1 desensitization.
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Background Hippocampus (HIP) was an important limbic structure, and concurrent emotion disorders may occur in medication-overuse headache patients. The aim of this study is to investigate altered HIP and HIP subfields volume in relation with the anxiety in medication-overuse headache patients using a state-of-the-art hippocampal segment method. ⋯ Conclusions The lower HIP and HIP subfields volume were identified in medication-overuse headache patients, and negatively related with anxiety condition. The potential mechanism for the comorbidity medication-overuse headache and anxiety might be interpreted as the reciprocal causation relationship and co-occurrence relationship.
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Etomidate is a preferred drug for the induction of general anesthesia in cardiovascular risk patients. As with propofol and other perioperatively used anesthetics, the application of aqueous etomidate formulations causes an intensive burning pain upon injection. Such algogenic properties of etomidate have been attributed to the solubilizer propylene glycol which represents 35% of the solution administered clinically. The aim of this study was to investigate the underlying molecular mechanisms which lead to injection pain of aqueous etomidate formulations. ⋯ Data in our study provided evidence that pain upon injection of clinical aqueous etomidate formulations is not an unspecific effect of hyperosmolarity but rather due to a specific action mediated by activated nociceptive TRPA1 and TRPV1 ion channels in sensory neurons.