Abnormalities in the intrinsic organization may be an underlying basis for the pronounced and prolonged negative bias in processing emotional information observed in MDD.

ObjectivesCurrent literature is in disagreement regarding female sex as a risk factor for pain after surgery. We hypothesized, that sex differences exist but that they are influenced by certain factors. Here, we investigated the influence of sex for different clinically relevant postoperative pain (POP) outcome parameters and evaluated the role of assumed confounders for sex differences.MethodsFrom 1372 screened patients undergoing orthopedic surgery at the university hospital of Muenster between March 2010 and June 2011, 890 patients were included. The validated International Pain Outcomes questionnaire was used to assess the role of sex for several aspects of POP including pain severity, physical and emotional functional interference as well as the patient’s perceptions of the care they received on the first day after surgery. Assessed confounders were age, preoperative chronic pain, anesthetic technique employed and surgical procedure. All statistical analyses were performed with SPSS Statistics Software 22.ResultsLinear regression analysis demonstrated that sex was a statistically significant risk factor for “worst pain since surgery”. Additionally, significant sex differences in “time spent in severe pain”, “feeling anxious due to pain”, “feeling helpless due to pain” and “opioid consumption since surgery” could be identified. An univariate general linear model showed that “age” and “preoperative pain” were significant confounders for sex differences. Further descriptive subgroup analysis revealed consistent sex differences for several POP outcome variables especially in patients older than 50 years or patients with preoperative chronic pain. However, sex differences disappeared in younger patients and in patients without preoperative pain.DiscussionOur data confirmed that sex differences exist in pain intensity and frequency, pain interference with feelings and opioid consumption during the first 24 hours postoperatively. However, sex differences were significantly influenced by the factors “age” and “preoperative pain”. These findings may in part explain why clinical studies get different results related to sex differences and renders specific awareness in older women and female patients with preoperative chronic pain.

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Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats.Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

Critical patients with COVID-19 are thought to be at high risk of developing chronic pain. However, the exact nature and mechanisms of COVID-19-related chronic pain remain largely unknown. Here, we describe clinical features, treatments and outcome of herpes zoster as well as postherpetic neuralgia in a 70-year-old woman with critical COVID-19. The patient had a history of type 2 diabetes and myasthenia gravis. She developed herpes zoster in the right 10 to 12 lumbar dermatomes in the recovery period of COVID-19. Intravenous (250 mg 3 times a day) and then oral (400 mg 5 times a day) acyclovir was used for antiviral therapy. Pregabalin (75 mg orally twice a day) and ibuprofen was used for analgesia. Her skin lesions resolved 21 days after the onset of rash. However, she continued to have persistent pain in the same dermatomal distribution. After the dosage of pregabalin was increased to 150 mg orally twice a day, her pain was partially relieved. During the telephone follow-up 4 months after herpes zoster eruption, the patient still complained intermittent pain in the right 10 to 12 lumbar dermatomes. Our case draws attention to postherpetic neuralgia in COVID-19 patients and provides a targeted suggestion for this kind of patients.

Background Common types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203 309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK. Methods A genome-wide association study was performed adjusting for age, sex, BMI and nine population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication. Results We identified three genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 × 10−11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 × 10−10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 × 10−8 for rs62053992. In the replication stage, among four significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). Conclusions We have identified three loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain.

Major histocompatibility class II (MHC II)-specific activation of CD4 T helper cells generates specific and persistent adaptive immunity against tumors. Emerging evidence demonstrates that MHC II is also involved in basic pain perception; however, little is known regarding its role in the development of cancer-induced bone pain (CIBP). In this study, we demonstrate that MHC II expression was markedly induced on the spinal microglia of CIBP rats in response to STAT1 phosphorylation. Mechanical allodynia was ameliorated by either pharmacological or genetic inhibition of MHC II upregulation, which was also attenuated by the inhibition of pSTAT1 and pERK but was deteriorated by intrathecal injection of IFNγ. Furthermore, inhibition of ERK signaling decreased the phosphorylation of STAT1, as well as the production of MHC II in vivo and in vitro. These findings suggest that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia.

Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases.