Articles: neuralgia.
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Cold allodynia is a common complaint of patients suffering from neuropathic pain initiated by peripheral nerve injury. However, the mechanisms that drive neuropathic cold pain remain elusive. In this study, we show that the interleukin (IL)-33/ST2 signaling in the dorsal root ganglion (DRG) is a critical contributor to neuropathic cold pain by interacting with the cold sensor transient receptor potential melastatin 8 (TRPM8). ⋯ Co-immunoprecipitation assays further reveal that ST2 interacts with TRPM8 in DRG neurons. Importantly, rIL-33-induced cold allodynia is abolished by pharmacological inhibition of TRPM8 and genetic ablation of the TRPM8-expressing neurons. Thus, our findings suggest that the IL-33/ST2 signaling mediates neuropathic cold pain through downstream cold-sensitive TRPM8 channels, thereby identifying a potential analgesic target for the treatment of neuropathic cold pain.
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Over 40% of neuropathic pain patients experience mood and cognitive disturbances, often showing reduced response to analgesics, with most affected individuals being female. This highlights the critical role of biological sex in pain-related affective and cognitive disorders, making it essential to understand the emotional and cognitive circuits linked to pain for improving treatment strategies. However, research on sex differences in preclinical pain models is lacking. ⋯ PERSPECTIVE: This manuscript reports the relevance of long-term investigations of sex differences in chronic pain. It shows differential development of somatosensory sensitivity, negative affective states and cognitive impairments in males and females. It emphasizes the importance of including subjects of both sexes in the investigation of pain-related mechanisms and therapeutic management.
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Comparative Study Observational Study
A Double-Blind Comparative Study of burstDR Versus Tonic Epidural Motor Cortex Stimulation for the Treatment of Intractable Neuropathic Pain.
Preliminary studies on epidural motor cortex stimulation (eMCS) for the treatment of drug-resistant neuropathic pain have supported the extension to novel stimulation waveforms, in particular burstDR. However, only a low level of evidence is available. The aim of this retrospective observational study was to compare the analgesic efficacy of burstDR versus tonic eMCS. ⋯ In the present paper, we provide for the first time a double-blinded study comparing burstDR versus tonic eMCS for the treatment of intractable, drug-resistant neuropathic pain. Our results show that burstDR eMCS is a promising option in a population of patients especially difficult to treat, and support the ongoing move toward new stimulation waveforms able to more efficiently activate the brain networks involved in pain modulation.
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Neuropathic pain poses a significant clinical challenge, largely due to the incomplete understanding of its molecular mechanisms, particularly the role of mitochondrial dysfunction. Bioinformatics analysis revealed that pyroptosis and inflammatory responses induced by spared nerve injury (SNI) in the spinal dorsal horn play a critical role in the initiation and persistence of neuropathic pain. Among the factors involved, TSPO (translocator protein) emerged as a key regulator. ⋯ Furthermore, Mendelian randomization analysis of GWAS data indicated that increased TSPO expression was linked to pain relief. Through drug screening, molecular docking, and behavioral assays, we identified zopiclone as a promising TSPO-targeting drug for pain treatment. In summary, this study enhances our understanding of the molecular interplay between TSPO, mitochondrial health, and neuropathic pain, highlighting TSPO as a potential therapeutic target for pain management.