The nonopioid actions of spinal dynorphin may promote aspects of abnormal pain after nerve injury. Mechanistic similarities have been suggested between opioid tolerance and neuropathic pain. Here, the hypothesis that spinal dynorphin might mediate effects of sustained spinal opioids was explored. Possible abnormal pain and spinal antinociceptive tolerance were evaluated after intrathecal administration of [D-Ala 2 , N-Me-Phe 4 , Gly-ol 5 ]enke phalin (DAMGO), an opioid agonist. Rats infused with DAMGO, but not saline, demonstrated tactile allodynia and thermal hyperalgesia of the hindpaws (during the DAMGO infusion) and a decrease in antinociceptive potency and efficacy of spinal opioids (tolerance), signs also characteristic of nerve injury. Spinal DAMGO elicited an increase in lumbar dynorphin content and a decrease in the receptor immunoreactivity in the spinal dorsal horn, signs also seen in the postnerve-injury state. Intrathecal administration of dynorphin A(1-17) antiserum blocked tactile allodynia and reversed thermal hyperalgesia to above baseline levels (i.e., antinociception). Spinal dynorphin antiserum, but not control serum, also reestablished the antinociceptive potency and efficacy of spinal morphine. Neither dynorphin antiserum nor control serum administration altered baseline non-noxious or noxious thresholds or affected the intrathecal morphine antinociceptive response in saline-infused rats. These data suggest that spinal dynorphin promotes abnormal pain and acts to reduce the antinociceptive efficacy of spinal opioids (i.e., tolerance). The data also identify a possible mechanism for previously unexplained clinical observations and offer a novel approach for the development of strategies that could improve the long-term use of opioids for pain.
Background: Infection is the most common complication of Idiopathic Nephrotic Syndrome (INS) and the main cause of INS recurrence, severe infection and even leading to mortality. The purpose of this study was to investigate the risk factors of severe infection in INS children and the clinical parameters influencing prognosis.Methods: Totally 147 children with INS and concomitant infections were enrolled and classified into the severe infection group (SIG) and Non-severe infection group (Non-SIG). The clinical characteristics and auxiliary examination results were compared between the two groups, and the early-warning parameters for severe infection and risk factors for poor prognosis were evaluated.Results: There were 49 patients in the SIG, 98 patients in the Non-SIG. In the SIG, the most common severe infections disease included severe pneumonia (63.6%), severe sepsis (30.6%), septic shock (4.1%). In SIG, Gram-positive bacteria (GPB) were more common, as was respiratory syncytial virus (RSV), and the three most common strains were Pseudomonas aeruginosa, Staphylococcus aureus (SA) and Staphylococcus epidermidis. There were more steroid-resistant nephrotic syndrome and combination of steroids and immunosuppressants in SIG, compared with the Non-SIG (P = 0.000). Patients in the SIG has lower complement 3 (C3, ≤ 0.55 g/L,) and absolute lymphocyte count (ALC, ≤ 1.5 × 109/L) (P = 0.004). Logistic regression analysis revealed that the independent risk factors for severe infections were the combined use of immunosuppressants [95% confidence interval (CI):1.569–463.541, P = 0.023], steroid resistance (95% CI: 4.845–2,071.880, P = 0.003), C-reactive protein (CRP) ≥8 mg/L (95% CI: 43.581–959, 935.668, P = 0.001), and infections caused by GPB (95% CI: 27.126–2,118, 452.938, P = 0.002), influenza (95% CI: 2.494–1, 932.221, P = 0.012) and RSV (95% CI: 5.011–24 963.819, P = 0.007). The patients in the SIG were classified into the survival group (N = 39) and the mortality group (N = 5). Logistic regression analysis showed that white blood cell count (WBC) >15 × 109/L (95% CI: 1.046–2.844, P = 0.033) was an independent risk factor of poor prognosis for these patients.Conclusions: Resistance to steroids, combined with steroids and IS agents, and GPB infections (especially SA) are high-risk factors for severe infection in children with INS. We should monitor CRP ≥ 8 mg/L, C3 ≤ 0.55 g/L and ALC ≤ 1.5 × 109/L to avoid developing severe infection. Accompanied by an increase in ANC, WBC significantly increased, suggesting a fatal infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.