Articles: neuropathic-pain.
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Low-dose ketamine infusion (LDKI) has shown effectiveness for treating acute pain associated with surgical and nonsurgical (traumatic, neuropathic, and acute cancer-related) origin as an adjuvant to opioids. The increasing use of LDKI as an opioid-sparing agent in multimodal analgesia requires a better understanding of its effects on the cardiovascular response, a known dose-dependent side effect of ketamine administration. We investigated the cardiovascular response of acute pain patients treated with LDKI. ⋯ Ketamine, adverse effects, tachycardia, hypertension, postoperative pain, chronic postsurgical pain.
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The compound NS5806 attenuates neuropathic pain via inhibiting extracellular signal-regulated kinase (ERK) activation in neuronal somata located at the dorsal root ganglion (DRG) and superficial spinal dorsal horn. NS5806 also reduces the expansion of DRG macrophages and spinal microglia several days after peripheral nerve injury, implying an anti-inflammatory effect. ⋯ Previous studies show that NS5806 only acts on neurons. This report unveils that NS5806 also acts on immune cells in the skin to exert its anti-inflammatory effects. Since NS5806 is lipid soluble for skin penetration, it suggests that NS5806 could also be developed into an anti-inflammatory drug for external use.
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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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Missing aspects of the heritability of chronic neuropathic pain, as a complex adult-onset trait, may be hidden within rare variants with low effect on disease risk, unlikely to be resolved by a single-variant approach. To identify new risk genes, we performed a next-generation sequencing of 107 pain genes and collapsed the rare variants through gene-wise aggregation analysis. The optimal unified sequence kernel association test was applied to 169 patients with painful neuropathy, 223 patients with nociplastic pain (82 diagnosed with chronic widespread pain and 141 with fibromyalgia), and 216 healthy controls. ⋯ Among the 32 patients harboring TRPA1 variants, 24 (75%) were diagnosed with nociplastic pain, either fibromyalgia (12; 37.5%) or chronic widespread pain (12; 37.5%), whereas 8 (25%) with painful neuropathy. Irrespective of the clinical diagnosis, 12 patients (38%) complained of itch and 10 (31.3%) of cold-induced or cold-accentuated pain, mostly episodic. Our study widens the spectrum of channelopathy-related chronic pain disorders and contributes to bridging the gap between phenotype and targeted therapies based on patients' molecular profile. [Figure: see text]
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Randomized Controlled Trial
Preliminary results from a randomized, controlled, cross-over trial of intrathecal oxytocin for neuropathic pain.
Compare intrathecal oxytocin, 100 µg to placebo on ongoing neuropathic pain and mechanical hyperalgesia and allodynia. ⋯ Although limited by the small number of subjects studied, oxytocin reduced pain more than placebo in all subjects. Further study of spinal oxytocin in this population is warranted.