Preoperative frailty predicts postoperative pain after total knee arthroplasty in older patients: a prospective observational study.

PURPOSE: Frailty is reportedly associated with postoperative adverse outcomes and may increase the risk of post-surgical pain. Our study aimed to explore whether frailty was an independent risk factor for pain after total knee arthroplasty (TKA) in older patients. METHODS: Included in this prospective observational study were patients aged 65 or older who underwent primary TKA. Frailty of the patients was assessed before surgery using the comprehensive geriatric assessment-frailty index and pain was evaluated before and after surgery using the Numerical Rating Scale. RESULTS: Of the 164 patients including 125 females with a mean age of 71.4 ± 4.6 years, 51 patients were identified as being frail. Patients with chronic post-surgical pain had a significantly higher frailty index than those without chronic post-surgical pain, which was the same in patients with acute post-surgical pain. After adjusting for other confounding factors, frailty was shown to be an independent risk factor for both acute (OR: 13.23, 95% CI 3.73-46.93, P < 0.001) and chronic post-surgical pain (OR: 4.24, 95% CI 1.29-14.00, P = 0.02). The area under the receiver operating characteristic curve for frailty predicting chronic post-surgical pain was 0.73 (P < 0.001, 95% CI 0.65-0.81). CONCLUSIONS: Our findings demonstrated that preoperative frailty in older patients was a predictor of acute and chronic post-surgical pain after TKA, suggesting that frailty assessment should become a necessary procedure before operations, especially in older patients.

Predictors of Chronic Pain in Elderly Patients Undergoing Total Knee and Hip Arthroplasty: A Prospective Observational Study.

BACKGROUND: Chronic postsurgical pain (CPSP) after total knee arthroplasty and total hip arthroplasty (TKA and THA) is an important clinical problem in which many factors play a role. The risk factors for CPSP in elderly individuals are currently unknown. Therefore, our aim was to predict the risk factors for CPSP after TKA and THA and to provide help regarding early screening and interventions for elderly individuals at risk. METHODS: In this prospective observational study, we collected and analyzed 177 TKA patients and 80 THA patients. Based on pain results at the 3-month follow-up, they were divided into the no chronic postsurgical pain and CPSP groups, respectively. The preoperative baseline conditions, including pain intensity (Numerical Rating Scale) and sleep quality (Pittsburgh Sleep Quality Index), as well as intraoperative and postoperative factors, were compared. Factors with P < .05 were included in binary regression analyses to establish prediction models for CPSP after TKA and THA. RESULTS: The prevalence of CPSP was 20.9% after TKA and 7.5% after THA. The preoperative sleep disorders were an independent risk factor of CPSP after TKA, but no risk factors of CPSP after THA were identified. CONCLUSION: This study indicated that the prevalence of CPSP after TKA was significantly higher than after THA, and that preoperative sleep disorders were an independent risk factor for CPSP after TKA, which may aid clinicians in screening people at risk for CPSP for primary prevention.

Association between single nucleotide variants and severe chronic pain in older adult patients after lower extremity arthroplasty.

BACKGROUND: Hip or knee osteoarthritis (OA) is one of the main causes of disability worldwide and occurs mostly in the older adults. Total hip or knee arthroplasty is the most effective method to treat OA. However, severe postsurgical pain leading to a poor prognosis. So, investigating the population genetics and genes related to severe chronic pain in older adult patients after lower extremity arthroplasty is helpful to improve the quality of treatment. METHODS: We collected blood samples from elderly patients who underwent lower extremity arthroplasty from September 2020 to February 2021 at the Drum Tower Hospital Affiliated to Nanjing University Medical School. The enrolled patients provided measures of pain intensity using the numerical rating scale on the 90th day after surgery. Patients were divided into the case group (Group A) and the control group (Group B) including 10 patients respectively by the numerical rating scale. DNA was isolated from the blood samples of the two groups for whole-exome sequencing. RESULTS: In total, 661 variants were identified in the 507 gene regions that were significantly different between both groups (P < 0.05), including CASP5, RASGEF1A, CYP4B1, etc. These genes are mainly involved in biological processes, including cell-cell adhesion, ECM-receptor interaction, metabolism, secretion of bioactive substances, ion binding and transport, regulation of DNA methylation, and chromatin assembly. CONCLUSIONS: The current study shows some variants within genes are significantly associated with severe postsurgical chronic pain in older adult patients after lower extremity arthroplasty, indicating a genetic predisposition for chronic postsurgical pain. The study was registered according to ICMJE guidelines. The trial registration number is ChiCTR2000031655 and registration date is April 6th, 2020.

S-Ketamine Pretreatment Alleviates Anxiety-Like Behaviors and Mechanical Allodynia and Blocks the Pro-inflammatory Response in Striatum and Periaqueductal Gray From a Post-traumatic Stress Disorder Model.

This study aims to explore the regulatory effect of S-ketamine on the mechanical allodynia, anxiety-like behaviors and microglia activation in adult male rats exposed to an animal model of post-traumatic stress disorder (PTSD). The rat PTSD model was established by the exposure to single-prolonged stress (SPS), and 1 day later, rats were intraperitoneally injected with 5 mg/kg S-ketamine or normal saline, respectively. Paw withdrawal mechanical threshold was measured 2 days before, and 1, 3, 5, 7, 10, 14, 21 and 28 days after injection to assess mechanical allodynia in the SPS-exposed rats. For anxiety-like behaviors, the open field test and elevated plus maze test were performed at 7 and 14 days after S-ketamine treatment in the SPS-exposed rats, respectively. SPS-induced rats presented pronounced mechanical allodynia and anxiety-like behaviors, which were alleviated by S-ketamine treatment. After behavioral tests, rats were sacrificed for collecting the anterior cingulate cortex (ACC), prefrontal cortex (PFC), dorsal striatum, and periaqueductal gray (PAG). Protein levels of TNF-α, IL-1ß, p-NF-κB, and NF-κB in brain regions were examined by Western blot. In addition, microglia activation in each brain region was determined by immunofluorescence staining of the microglia-specific biomarker Iba-1. Interestingly, pro-inflammatory cytokines were significantly upregulated in the dorsal striatum and PAG, rather than ACC and PFC. Activated microglia was observed in the dorsal striatum and PAG as well, and upregulated p-NF-κB was detected in the dorsal striatum. Inflammatory response, phosphorylation of NF-κB and microglia activation in certain brain regions were significantly alleviated by S-ketamine treatment. Collectively, S-ketamine is a promising drug in alleviating mechanical allodynia, anxiety-like behaviors, and pro-inflammatory responses in discrete brain regions in a model of PTSD.