Articles: neuropathic-pain.
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Post-traumatic trigeminal neuropathic pain (PTNP) following trigeminal neuralgia (TN)-related neuroablative procedures is relatively rare. Due to the fear of debilitating complications, its treatment has been generally suboptimal. Pregabalin (PGB) has been reported to relieve neuropathic pain. However, the potential role of PGB and the predictors of response of PGB use as a strategy in the treatment of PTNP following TN-related neuroablative procedures have not been identified yet. ⋯ Post-traumatic trigeminal neuropathic pain, efficacy, safety, predictor of response, pregabalin.
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Spinal cord injury (SCI)-induced neuropathic pain (SCI-NP) develops in up to 60 to 70% of people affected by traumatic SCI, leading to a major decline in quality of life and increased risk for depression, anxiety, and addiction. Gabapentin and pregabalin, together with antidepressant drugs, are commonly prescribed to treat SCI-NP, but their efficacy is unsatisfactory. The limited efficacy of current pharmacological treatments for SCI-NP likely reflects our limited knowledge of the underlying mechanism(s) responsible for driving the maintenance of SCI-NP. ⋯ We found that both TTA-P2 and gabapentin reduced mechanical hypersensitivity in male and females SCI rats, but surprisingly only TTA-P2 reduced spontaneous ongoing pain in male SCI rats. PERSPECTIVES: SCI-induced neuropathic pain, and in particular the spontaneous ongoing pain component, is notoriously very difficult to treat. Our data provide evidence that inhibition of T-type calcium channels reduces spontaneous ongoing pain in SCI rats, supporting a clinically relevant role for T-type channels in the maintenance of SCI-induced neuropathic pain.
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Nerve injury outcomes might be predicted by examining small extracellular vesicles (sEVs) in circulation, as their biomolecular cargo facilitates cellular communication and can alter transcriptional state and behavior of recipient cells. We found that sEVs from the serum of spared nerve injury (SNI) model male mice had 7 differentially expressed miRNAs compared to sEVs from sham-operated control mice 4 weeks postsurgery. We investigated how these sEVs alter transcription in primary cortical microglia, a crucial mediator of neuropathic pain, using RNA sequencing. ⋯ Thus, when using sEVs from sham mice as control in comparative mechanistic studies after nerve injury, sex of mice should be taken into consideration. PERSPECTIVE: Microglial uptake of sEVs from male sham control mice induces higher pro-inflammatory responses compared to SNI sEVs but the reverse was observed upon treatment with sEVs from female mice. Wound healing may have a long-term impact on sEVs in male mice and should be considered for comparative studies using sEVs.
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Spinal cord injury (SCI) results in the loss of motor and sensory function from disconnections between efferent and afferent pathways. Most SCI patients are affected with chronic neuropathic pain, but there is a paucity of data concerning neuroplastic changes following SCI. Chronic pain disrupts default networks and is associated with abnormal insular connectivity. The posterior insula (PI) is associated with the degree of pain and intensity of pain. The anterior insula (AI) is related to signal changes. Comprehension of SCI pain mechanisms is essential to elucidate effective treatment options. ⋯ These findings illustrate that there is a complex hyperconnectivity and modulation of pain pathways after traumatic SCI.
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The origin of chronic pain is linked to inflammation, characterized by increased levels of proinflammatory cytokines in local tissues and systemic circulation. Transforming growth factor beta-activated kinase 1 (TAK1) is a key regulator of proinflammatory cytokine signaling that has been well characterized in the context of cancer and autoimmune disorders, yet its role in chronic pain is less clear. Here, we evaluated the ability of our TAK1 small-molecule inhibitor, takinib, to attenuate pain and inflammation in preclinical models of inflammatory, neuropathic, and primary pain. ⋯ Overall, our results support the therapeutic potential of TAK1 as a novel drug target for the treatment of chronic pain syndromes with different etiologies. PERSPECTIVE: This article reports the therapeutic potential of TAK1 inhibitors for the treatment of chronic pain. This new treatment has the potential to provide a greater therapeutic offering to physicians and patients suffering from chronic pain as well as reduce the dependency on opioid-based pain treatments.