Korean Journal of Pain最新文献

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.

Background: Elderly patients with herpes zoster ophthalmicus (HZO) have a high risk to progress to postherpetic neuralgia (PHN). Thus, early implementation of optimal treatment could lower the prevalence of PHN.

Methods: We collected 50 elderly acute HZO patients treated with short-term peripheral nerve stimulation (PNS) or supraorbital nerve pulsed radiofrequency (PRF) from three hospitals from October 2022 to October 2023. All patients completed 12-month follow-up. The Visual Analog Scale (VAS), Barrow Neurological Institute (BNI) score and Pittsburgh Sleep Quality Index (PSQI) were used to assess the pain intensity and sleep quality.

Results: The pain intensity and sleep quality of all patients was significantly relieved after surgery. Following surgery, the PNS group's VAS and PSQI scores were statistically lower than those of the PRF group, and they also took less medication. At 3 months after surgery, the incidence of clinically significant PHN in the PNS group was lower than the PNS group. At 12 months after surgery, the BNI scores of the PNS group were better than the PRF group.

Conclusions: Early application of short-term PNS or PRF for acute-phase HZO in the elderly can relieve pain. Compared to PRF, PNS may offer superior pain management, enhance quality of life, and contribute to a downward trend in the incidence of PHN.

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.

A compound paradox has been identified in the revised (2020) International Association for the Study of Pain (IASP) definition of pain, such that it simultaneously prescribes a connection between pain and tissue damage and allows that prescription to be violated. In a narrative form, the objective of this paper is to reveal these paradoxes and to offer a pathway to their resolution, thus clarifying the definition of pain for the purposes of scientific study and clinical application. The first paradox is that contradictory true positions can be held, when the experiencer claims to be "in pain" and the observer cannot find the required association with tissue damage or, preferably as is argued, nociception. The second paradox is revealed by the construct of "nociplastic" pain, which contradicts the IASP definition to the extent that nociceptors have not been activated, yet at the same time is consistent with that definition to the extent that it "resembles" an experience associated with actual or potential tissue damage. In the interests of all concerned parties, the IASP definition of pain can be strengthened by removing the current ambiguity of interpretation, grounding the experience in a reconceptualisation of nociception as activation of a nociceptive apparatus, and clearly distinguishing it from suffering.

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.

Background: Fibromyalgia (FM) and major depressive disorder (MDD) frequently co-occur. This study investigated whether the differences in resting-state functional connectivity (rs-FC) of the emotion- and pain-related brain networks may differentiate FM patients with and without MDD and if these differences are associated with the severity of clinical symptoms, quality of life, recurrent depression, pain catastrophizing, and antidepressant use.

Methods: In this study, the authors recruited a sample of 37 females classified as FM with MDD (FM + MDD, n = 23) or FM without MDD (FM-only, n = 14) based on the International Neuropsychiatric Interview. The severity of depressive symptoms was measured using the Beck Depression Inventory-II (BDI-II).

Results: Age-adjusted rs-FC correlated significantly with BDI-II scores. FM + MDD patients showed increased rs-FC between the right ventral insula and left middle frontal gyrus (MFG) (χ²(1) = 5.54, P = 0.019, effect size [ES] = 0.87), and decreased rs-FC between the caudal hippocampus and middle cingulate cortex (χ²(1) = 6.65, P < 0.001, ES = 0.90). Increased rs-FC between the ventral insula and MFG was positively associated with recurrent MDD and pain catastrophizing, and negatively with FM-related quality of life. The connection between the left MFG and the right posterior parietal thalamus is associated with recurrent MDD and pain catastrophizing.

Conclusions: Distinct neurofunctional patterns in regions related to emotional regulation and cognitive control of pain-marked by increased inter-hemispheric frontal and decreased intra-hemispheric limbic-cingulate connectivity-may serve as potential biomarkers to distinguish FM patients with comorbid MDD from those without.