Korean Journal of Pain最新文献

Background: The involvement of antinociceptive centers in neurodegeneration within the brain, particularly in Parkinson's disease (PD), which is accompanied by chronic pain, is not yet well understood.

Methods: Electrophysiological recordings were conducted on 15 king albino rats across three experimental conditions: intact, a rotenone-induced PD model, and a PD model treated with hydrocortisone. Extracellular spike activity was recorded from 241 single neurons in the periaqueductal gray (PAG) in response to stimulation of the raphe magnus nucleus (RMG).

Results: The PD model exhibited significant excitotoxicity in the recorded neurons, indicative of substantial neurodegeneration, which appeared to precede both depressor (tetanic depression [TD], post-tetanic depression [PTD]) and excitatory (tetanic potentiation [TP], post-tetanic potentiation [PTP]) post-stimulus effects. A mathematical analysis of pre- and post-stimulus activation frequencies revealed the following: in the PD model with hydrocortisone protection, compared to the unprotected PD model, the pre-stimulus activation frequency of PAG neurons during high-frequency stimulation of the RMG was reduced, bringing the values closer to normal levels. The post-stimulus activation frequency of PAG neurons in the treatment group also decreased, both in depressor (TD, PTD) and excitatory (TP, PTP) responses, approaching normal levels.

Conclusions: These findings, in conjunction with the previous research on the protective role of hydrocortisone in depressive reactions, suggest that hydrocortisone effectively mitigates excitotoxicity and provides significant neuroprotection in the context of PD.

Background: Weakness in the quadriceps muscle significantly contributes to the development and progression of knee osteoarthritis (OA), characterized by pain and impaired function. This study aimed to assess structural and functional recovery in the quadriceps and its association with knee OA pain following treatment with the Muscle Enhancement and Support Therapy (MEST) device. MEST involves inserting cog polydioxanone filaments directly into muscle tissue to help alleviate OA pain.

Methods: Knee OA was induced in Sprague-Dawley rats using monoiodoacetate injections, followed by MEST or a sham treatment. Five weeks post-MEST treatment, quadriceps recovery was evaluated by measuring entire muscle volume, hindlimb torque, tissue morphology, and key structural and functional biomarkers. Pain was assessed through paw withdrawal thresholds and weight-bearing distribution. Correlations between muscle measurements and pain levels were then analyzed.

Results: MEST treatment resulted in significant increases in quadriceps volume, enhanced hindlimb torque, and elevated expression of α-actin, myosin, and the mitochondrial marker cytochrome c oxidase subunit 4, along with reductions in OA pain. These enhancements in muscle condition were closely associated with pain relief in OA.

Conclusions: This study shows that MEST improves the quadriceps condition, including muscle volume, structure, function, and energy metabolism, and relieves knee OA pain, which are closely linked. These findings may suggest that promoting quadriceps recovery through MEST could be a promising approach for managing OA-related pain.

Background: Prenatal chronic stress can impact pain sensitivity and analgesic responses in offspring. This study investigates oxidative stress markers in the ovaries of female rats that experienced unpredictable chronic mild stress (UCMS) before pregnancy and development of morphine analgesic tolerance in their offspring.

Methods: In this experimental study, 23 adolescent Wistar rats, 22 female and one male (6-8 weeks), were used as breeding pairs. The rats were maintained in a controlled environment with a 12-hour light/dark cycle and had unrestricted access to food and water. For one month prior to mating, the female rats were subjected to UCMS. After this exposure, the females were mated with a single male rat. Following lactation, male offspring received a daily dose of 10 mg/kg morphine intraperitoneally for 7 days, and the analgesic effects of morphine were assessed using the hot plate test. Ovarian tissues from the female rats exposed to UCMS were analyzed for oxidative stress markers.

Results: Pre-pregnancy UCMS significantly reduced morphine's antinociceptive potency, with the peak effect on day 1 being stronger in the stressed group (P < 0.0001). The cumulative antinociceptive effect over 7 days was significantly higher in the morphine-unstressed group (P < 0.01). UCMS increased malondialdehyde levels and decreased glutathione (P < 0.01), superoxide dismutase and catalase activities in maternal ovarian tissues (P < 0.05).

Conclusions: Maternal UCMS increased oxidative stress markers in the ovaries and might relate to altered morphine antinociceptive potency in offspring, suggesting epigenetic effects of parental stress on pain management in future generations.

Background: Although intravenous (IV) acetaminophen (AAP) may help reduce severe postoperative pain and opioid use after cardiovascular surgery, its effectiveness must be further validated. Therefore, the authors aimed to evaluate the analgesic efficacy of perioperative IV AAP in patients undergoing cardiovascular surgery by conducting this meta-analysis.

Methods: A comprehensive literature search was conducted of PubMed, Embase, CENTRAL, CINAHL, Scopus, and Web of Science databases for studies published up to March 21, 2024. Six randomized controlled trials comparing IV AAP with a placebo in cardiovascular surgery were included. The mean difference (MD) was calculated to estimate pooled effect sizes. The primary outcome was opioid consumption, measured in morphine equivalent dose, and the secondary outcome was postoperative pain score.

Results: Postoperative opioid consumption was significantly reduced with IV AAP than it was with a placebo (MD: -21.68, 95% confidence interval [CI]: -38.41 to -4.95, P = 0.011). Significant reductions in postoperative pain scores were observed at 6 hours (MD: -0.76, 95% CI: -1.43 to -0.10, P = 0.025) and 24 hours (MD: -0.63, 95% CI: -1.02 to -0.25, P = 0.001) after surgery. However, these reductions did not meet clinically meaningful thresholds. No significant differences were observed at 12, 18, and 48 hours postoperatively.

Conclusions: IV AAP was more effective than a placebo for postoperative adjunct analgesia in patients who underwent cardiovascular surgery.

Background: Primary stabbing headache (PSH) is commonly seen in headache clinics, yet its long-term course remains inadequately explored. This study aimed to determine the 2-year recurrence rate of PSH and to identify associated risk factors.

Methods: Out of 1,756 patients who visited a specialized headache clinic due to headache complaints, 106 patients diagnosed with PSH were enrolled consecutively. Demographic and clinical information was collected, along with the time to achieve complete remission post-treatment. To evaluate the 2-year prognosis, all participants were contacted through telephone interviews. A total of 106 patients were interviewed by telephone at least 2 years after the onset of PSH. The authors examined the frequency and features of PSH recurrence and assessed clinical variables potentially linked to its recurrence.

Results: A recurrence of PSH occurred in 36.3% of the patients. Patients with recurrent PSH had more prior history of stabbing headache (55.2% vs. 29.4%, P = 0.023), comorbid migraine (17.2% vs. 3.9%, P = 0.043) and severe intensity of stabbing headache (41.4% vs. 17.7%, P = 0.020) than those with non-recurrent PSH. Multivariable Cox regression analysis revealed that an independent effect of comorbid migraine on the recurrence of PSH (adjusted hazard ratio, 2.791; 95% confidence interval, 1.012-7.701; P = 0.047).

Conclusions: Over one-third of individuals diagnosed with PSH experienced a recurrence within 2 years of the initial episode. Comorbid migraine was related to a recurrence of PSH, suggesting the potential role of shared pathophysiological mechanisms between migraine and PSH in influencing the prognosis of PSH.

Background: This systematic review and meta-analysis analyzed the utility of the Analgesia Nociception Index (ANI) in detecting intraoperative and procedural pain in sedated patients.

Methods: A comprehensive search of the Cochrane Central Register of Controlled Trials, Ovid-MEDLINE, Ovid-Embase, and Google Scholar databases was performed to identify relevant studies. The primary outcome was the diagnostic accuracy of ANI, assessed by pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR). Secondary outcomes were the correlation between ANI and pain assessment scales, the effect of norepinephrine (NE) on ANI, and differences in opioid consumption between the ANI-guided and control groups.

Results: Eleven studies were included in the systematic review, with ten studies incorporated into the meta-analysis. ANI demonstrated moderate sensitivity (0.746, 95% confidence interval [CI] = 0.683-0.803) and specificity (0.776, 95% CI = 0.741-0.808) for detecting intraoperative and procedural pain, with a pooled DOR of 10.491. ANI was lower in the pain state than that in the no-pain state (standardized mean difference [SMD] = -1.140, 95% CI = -1.239 to -1.041, I² = 93.63%). ANI-guided analgesia was associated with a significant reduction in opioid consumption (SMD = -0.410, 95% CI = -0.643 to -0.178, I² = 0.0%). There were no significant differences in ANI between the NE and control groups. ANI showed a negative correlation with pain scales (r = -0.110 to -0.470).

Conclusions: ANI effectively differentiated between the pain and non-pain states in sedated patients with moderate diagnostic accuracy and helped reduce opioid consumption. However, the high heterogeneity suggests the need for cautious interpretation.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment.

Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs.

Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice's mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4.

Conclusions: Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research. This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship.

Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders.

Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP. Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively.

Conclusions: The authors' findings demonstrate that the importance of education and smoking in understanding chronic pain's pathogenesis, which is important for the primary prevention and prognosis of chronic pain.