Articles: neuralgia.
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Neuropathic pain is a common clinical complication of nerve injury, and the effective treatment of neuropathic pain is still challenging. Ligustrazine is mainly used for the treatment of cardiovascular disease and its role in neuropathic pain is less investigated. The purpose of our study was to explore the effects of ligustrazine on neuropathic pain, as well as the underlying molecular mechanism. ⋯ Our results suggest that ligustrazine could effectively attenuate neuropathic pain by inhibition of Janus Kinase (JAK)/STAT3 pathway in CCI rats.
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Curcumin has been shown to possess strong anti-inflammatory activity in many diseases. It has been demonstrated that the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade and the NAcht leucine-rich-repeat protein 1 (NALP1) inflammasome are important for the synthesis of Pro-Interleukin (IL)-1β and the processing of the inactive protein to its mature form, which plays an active role in the pathogenesis of neuropathic pain. ⋯ Furthermore, the genetic down-regulation of NALP1 inflammasome activation by NALP1 siRNA and the pharmacological inhibition of the JAK2-STAT3 cascade by AG490 markedly inhibited IL-1β maturation and Pro-IL-1β synthesis, respectively, and reduced SNI-induced pain hypersensitivity. Our results suggest that curcumin attenuated neuropathic pain and down-regulated the production of spinal mature IL-1β by inhibiting the aggregation of NALP1 inflammasome and the activation of the JAK2-STAT3 cascade in astrocytes.
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J. Oral Maxillofac. Surg. · Jul 2016
Factors Determining Outcome After Trigeminal Nerve Surgery for Neuropathic Pain.
Most patients who seek relief from trigeminal neuropathic pain by trigeminal microneurosurgery techniques do not show permanent pain relief after surgery. However, a small number of patients have permanent relief after surgery. The objective of this study was to determine factors that might be associated with the resolution, decrease, or recurrence of neuropathic pain after trigeminal nerve surgery in those patients who present with neuropathic pain before surgery. ⋯ The recurrence of neuropathic pain after trigeminal nerve repair for neuropathic pain is likely multifactorial and might not depend on factors that normally affect sensory recovery in patients who have no neuropathic pain (ie, age, duration of injury, type of injury, or repair type) and undergo trigeminal nerve surgery. These differences indicate that the understanding of trigeminal neuropathic pain is incomplete. Predictive outcomes of treatment will probably improve when the etiology is better defined to allow target- and site-specific treatment. In the meantime, trigeminal nerve surgery is a treatment option that offers a chance of decreasing or resolving pain intensity.
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It seems that central neuropathic pain (CNP) is associated with altered abilities to modulate pain; whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution, enhanced pain excitation is associated with the intensity of chronic pain. We investigated the hypothesis that CNP is associated with decreased descending pain inhibition along with increased neuronal excitability and that both traits are associated with spinothalamic tract (STT) damage. Chronic spinal cord injury subjects with CNP (n = 27) and without CNP (n = 23) and healthy controls (n = 20) underwent the measurement of pain adaptation, conditioned pain modulation (CPM), tonic suprathreshold pain (TSP), and spatial summation of pain above injury level. ⋯ Thus, top-down processes may determine the spread of CNP, whereas bottom-up processes may determine CNP intensity. It also seems that the mechanisms of CNP may involve STT-induced hyperexcitability. Future, longitudinal studies may investigate the timeline of this scenario.
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Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2.2) channel as an alternative to direct channel block. ⋯ Using constellation pharmacology, a recently described high content phenotypic screening platform for functional fingerprinting of neurons that uses subtype-selective pharmacological agents to elucidate cell-specific combinations (constellations) of key signaling proteins that define specific cell types, we investigated if (S)-LCM preferentially acts on certain types of neurons. (S)-lacosamide decreased the dorsal root ganglion neurons responding to mustard oil, and increased the number of cells responding to menthol. Finally, (S)-LCM reversed thermal hypersensitivity and mechanical allodynia in a model of postoperative pain, and 2 models of neuropathic pain. Thus, using (S)-LCM to inhibit CRMP2 phosphorylation is a novel and efficient strategy to treat pain, which works by targeting specific sensory neuron populations.