Korean Journal of Pain最新文献

Neuropathic pain (NP) is a chronic pain condition resulting from damage or disease in the nervous system. It is characterized by hyperalgesia, spontaneous pain, and mechanical allodynia. Due to limited treatment options, NP significantly impairs the quality of life of affected individuals. Recent research has highlighted the critical role of microglia in the initiation and maintenance of NP, however, the underlying mechanisms remain incompletely understood. Existing evidence suggests that signaling pathways, including NF-κB, PI3K/Akt/mTOR, p38MAPK, JAK2/STAT3, and Nrf2/HO-1, contribute to microglial activation and the modulation of NP. This review explores the key activation molecules in these pathways, the microglial phenotype, and associated inflammatory processes. Additionally, the authors summarize the latest literature and application prospects of certain drugs/compounds/ non-invasive treatments, aiming to provide a theoretical basis for the development of novel microglia-targeted therapies.

Background: The spinal nerve ligation (SNL) model induces neuropathic pain through peripheral nerve injury, leading to central sensitization and neuroinflammation. Recent evidence suggests that activation of Mincle (macrophage-inducible C-type lectin) in the spinal cord may also trigger pain hypersensitivity without peripheral nerve injury. This study compared the effects of SNL and spinal Mincle activation on pain behavior and neuroglial activation.

Methods: Pain hypersensitivity was evaluated following a single intrathecal (i.t.) injection of the Mincle ligand, trehalose-6,6'-dibehenate (TDB) at doses of 0.1 μg, 1 μg, or 10 μg (single injection, S-TDB). In a separate group, rats received repeated i.t. TDB injection (10 μg/day for 2 days, R-TDB) or surgery for SNL. Pain behaviors were assessed for 28 days. Spinal expression of microglia (Iba1) and astrocytes (GFAP) was analyzed via immunofluorescence in R-TDB and SNL groups.

Results: I.t. TDB administration at all tested doses produced significant pain hypersensitivity from day 1 to day 28, with no clear dose-dependent effects. Repeated i.t. TDB administration led to greater mechanical allodynia than S-TDB, but thermal responses were similar. Compared to SNL, the R-TDB group produced a comparable pain hypersensitivity to SNL but exhibited faster activation of microglia and astrocytes.

Conclusions: Spinal Mincle receptor activation via i.t. TDB induces persistent pain hypersensitivity in the absence of peripheral nerve injury, accompanied by a more rapid neuroinflammatory response than that observed in the SNL model. These findings support Mincle activation as a potential experimental model for neuroinflammationassociated neuropathic pain.

Background: Neuropathic pain (NP) is a complex and intractable chronic pain condition. This study aims to clarify the functional role of lncRNA HOTTIP in NP.

Methods: A chronic constriction injury (CCI) surgery was used to establish a NP rat model. Lipopolysaccharide (LPS) stimulation was employed to activate BV2 cells. Intrathecal administration of HOTTIP-targeting lentiviral vectors and antagomiR-216a-5p was performed to lower HOTTIP and miR-216a-5p expression. RT-qPCR analyzed HOTTIP, miR-216a-5p, and inflammatory markers (cyclooxygenase-2 [COX-2], inducible nitric oxide synthase [INOS], toll-like receptor 4 [TLR4]) in rat dorsal root ganglion and BV2 cells to evaluate their roles in NP, while also tracking pain behavior changes in CCI rats to correlate molecular targets with pain perception. ELISA measured anti-inflammatory (interleukin [IL]-4) and pro-inflammatory (IL-6, tumor necrosis factor [TNF]-α) factor levels to quantify inflammation and evaluate inflammatory response severity. A specific binding relationship between HOTTIP and miR-216a-5p was evaluated using bioinformatics prediction, dual-luciferase reporter assays, and RNA pull-down techniques.

Results: In a rat model of CCI, inhibition of HOTTIP attenuated NP, decreased pro-inflammatory mediators (TNF-α, IL-6, COX-2, INOS, TLR4), and increased IL-4. In LPS-induced BV2 cells, inhibition of HOTTIP also exhibited antiinflammatory effects. HOTTIP targeted binding to miR-216a-5p. Inhibition of miR-216a-5p significantly counteracted the inhibitory effects of silencing HOTTIP on NP and neuroinflammatory responses. In addition, Janus kinase 2 (JAK2) was found to be a direct target of miR-216a-5p.

Conclusions: HOTTIP contributes to the worsening of NP and neuroinflammation by modulating the miR-216a-5p/JAK2 pathway, exerting analgesic protective effects, indicating its potential as a therapeutic target for NP.

Neuropathic pain remains a major challenge in pain management because of its complex mechanisms and suboptimal response to conventional treatments, which often provide incomplete relief and carry the risk of adverse effects. Injections of 5% glucose in water (D5W) delivered via intradermal, subcutaneous, fascial, or perineural glucopuncture have emerged as a minimally invasive and safe therapeutic option. Although the exact mechanism has not been fully elucidated, the proposed pathways include transient receptor potential vanilloid 1 modulation, suppression of neurogenic inflammation, and stabilization of C-fiber excitability. Clinical studies, ranging from case reports to randomized controlled trials, have suggested the efficacy of this approach in postherpetic neuralgia, entrapment neuropathies, chronic tendinopathies, and fascial pain, with minimal complications. Unlike prolotherapy, glucopuncture uses isotonic glucose (D5W), and primarily exerts neuromodulatory rather than regenerative effects. Current evidence, while limited, indicates meaningful and sustained pain relief in selected neuropathic conditions with a favorable safety profile and low procedural complexity. This review outlines key mechanisms, clinical outcomes, differences between related interventions, and clinical considerations.

Background: Ultrasound-guided abdominal wall blocks are increasingly used to enhance postoperative analgesia in laparoscopic nephrectomy. Among these, the transversus abdominis plane (TAP) block and the quadratus lumborum (QL) block have emerged as promising techniques. However, no comprehensive review has yet compared the analgesic efficacy of these two regional approaches.

Methods: An extensive search was conducted across MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar to identify randomized controlled trials comparing the postoperative analgesic effects of the TAP block, QL block, and systemic analgesia. The primary outcome was 24-hour opioid consumption, standardized to intravenous morphine milligram equivalents (MME). Secondary outcomes included postoperative pain scores assessed using a 0-10 Visual Analog Scale (VAS). A minimal clinically important difference (MCID) was defined as a reduction of 10 mg MME or 1 point on the VAS.

Results: Twelve studies were included. Both TAP and QL blocks significantly reduced opioid consumption compared to systemic analgesia (mean difference [95% confidence interval, CI]: QL, -11.42 mg [-18.88 to -3.97]; TAP, -10.88 mg [-17.49 to -4.26]). However, the 95% CI did not meet the predefined MCID of -10 mg. Similarly, improvements in postoperative pain scores did not reach clinical significance.

Conclusions: While TAP and QL blocks demonstrated a significant analgesic effect compared to systemic analgesia, the clinical relevance of this benefit may be limited.

Background: Antiepileptic drugs have shown promise in treating acute nociceptive pain. Bioisosterism is a crucial strategy in analgesic development, enabling molecular modifications that improve therapeutic efficacy and safety. This study aims to develop and evaluate new compounds based on the concept of bioisosterism, synthesizing organocomplexes derived from compounds with established analgesic properties.

Methods: A novel prototype, Zn(Valp)₂Bipy was synthesized, characterized, and tested for antinociceptive and toxicological effects in mice. The compound was administered orally at different doses to evaluate inhibition of acetic acid-induced abdominal constrictions and both phases of the formalin test. Additional evaluation included hot plate and tail immersion assays for central antinociception, the open field test for motor coordination, and a 14-day regimen for subacute toxicity.

Results: Zn(Valp)₂Bipy (0.1, 1, and 10 mg/kg) significantly reduced abdominal constrictions and licking time in both phases of the formalin test. In the hot plate and tail immersion tests, this treatment significantly increased the latency period, indicating enhanced pain tolerance. Notably, the analgesic effect observed in the hot plate test was reversed by naloxone, suggesting an opioid-like action. Furthermore, in the open field test, the treatment did not affect the animals' motor function. When administered daily at a dose of 1 mg/kg for 14 days, the compound exhibited no observable toxicity, underscoring its safety profile.

Conclusions: Zn(Valp)₂Bipy demonstrated significant antinociceptive activity through central and peripheral mechanisms without detectable toxicity. This study provides the first evidence of analgesic potential for this complex, highlighting it as a promising drug prototype for effective pain management therapies.