Articles: hyperalgesia.
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To explore the role of P2Y6 receptors in the maintenance of neuropathic pain and progression of oxidative stress, we investigated the efficacy of the selective P2Y6 receptors antagonist MRS2578 on the antiallodynic effects and improvement of pathological neuropathic pain-induced oxidative stress, thereby finding a potential therapeutic target in neurological disease. ⋯ The results demonstrated that inhibition of the P2Y6 receptor can generate antiallodynic effects and improved the pathological neuropathic pain-induced oxidative stress. Thus, this study provides a potential approach for the therapy of neurological disease.
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Neuropathic pain is a chronic condition that occurs frequently after nerve injury and induces hypersensitivity or allodynia characterized by aberrant neuronal excitability in the spinal cord dorsal horn. Fibronectin leucine-rich transmembrane protein 3 (FLRT3) is a modulator of neurite outgrowth, axon pathfinding, and cell adhesion, which is upregulated in the dorsal horn following peripheral nerve injury. However, the function of FLRT3 in adults remains unknown. ⋯ Conversely, FLRT3 inhibition with antibodies attenuated mechanically induced pain after nerve damage. These findings suggest that FLRT3 is produced by injured DRG neurons and increases neuronal excitability in the dorsal horn, leading to pain sensitization. Neuropathic pain induction is a novel function of FLRT3.
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p53 and parkin are involved in mitochondrial quality control. The present study aimed to characterize the functional significance of parkin/p53 in the development of mitochondrial dysfunction and the pathophysiology of neuropathic pain in type I diabetes. Type I diabetes was induced in mice (N = 170) using streptozotocin (STZ). ⋯ Methylglyoxal also decreased mitochondrial membrane potential in cultured DRG neurons. Alteration of p53/parkin expression produces mitochondrial dysfunction and ROS accumulation, leading to pain hypersensitivity in diabetic or methylglyoxal treated mice. Methylglyoxal produces neurological derangements similar to diabetes, via direct mechanisms on DRG neurons.
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Int J Environ Res Public Health · Sep 2019
ReviewDoes Rebound Pain after Peripheral Nerve Block for Orthopedic Surgery Impact Postoperative Analgesia and Opioid Consumption? A Narrative Review.
Regional anesthesia has been considered a great tool for maximizing post-operative pain control while minimizing opioid consumption. Post-operative rebound pain, characterized by hyperalgesia after the peripheral nerve block, can however diminish or negate the overall benefit of this modality due to a counter-productive increase in opioid consumption once the block wears off. We reviewed published literature describing pathophysiology and occurrence of rebound pain after peripheral nerve blocks in patients undergoing orthopedic procedures. ⋯ Multimodal strategies including preemptive analgesia before the block wears off, intra-articular or intravenous anti-inflammatory medications, and use of adjuvants in nerve block solutions may reduce the burden of rebound pain. Additionally, patient education regarding the possibility of rebound pain is paramount to ensure appropriate use of prescribed pre-emptive analgesics and establish appropriate expectations of minimized opioid requirements. Understanding the impact of rebound pain and strategies to prevent it is integral to effective utilization of regional anesthesia to reduce negative consequences associated with long-term opioid consumption.
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Opioid-induced hyperalgesia (OIH) is a serious adverse event produced by opioid analgesics. Lack of an in vitro model has hindered study of its underlying mechanisms. Recent evidence has implicated a role of nociceptors in OIH. ⋯ We report on an in vitro model of nociceptor neuroplasticity mediating this opioid-induced hyperalgesia (OIH) and priming induced by fentanyl. Using this model, we have found qualitative and quantitative differences between cultured nociceptors from opioid-naive and opioid-primed animals, and provide evidence for the important role of nociceptor μ-opioid receptor-mediated calcium signaling and peripheral protein translation in the weakly IB4-binding population of nociceptors in OIH. These findings provide information useful for the design of therapeutic strategies to alleviate OIH, a serious adverse event of opioid analgesics.