Accepted

Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single-population studies have limited generalisability as socio-economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre-operative patient and clinical characteristics and EQ-5D-3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire-revised; brief symptom inventory-18; perceived stress scale; mechanical temporal summation; and pressure-pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74-0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03-21.22); pre-operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11-1.96); previous mastitis (OR 4.90, 95%CI 1.31-18.34); and perceived stress scale (OR 1.35, 95%CI 1.01-1.80 per 5 points), after adjusting for: enrolment site; pre-operative pain score at the breast; pre-operative overall pain score at rest; postoperative non-steroidal anti-inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre-emptive interventions to reduce persistent pain risk.

The simultaneous use of drugs with different mechanisms of analgesic action is a strategy for achieving effective pain control while minimizing dose-related side effects. Choline was described to potentiate the analgesic action of parecoxib sodium at small doses in several inflammatory pain models. However, these findings are still very limited, and more associated data are required to confirm the effectiveness of the combined choline and parecoxib sodium therapy against inflammatory pain.

Free drug concentration in the blood sera is crucial for its appropriate activity. Serum albumin, the universal blood carrier protein, is responsible for transporting drugs and releasing them into the bloodstream. Therefore, a drug's binding to SA is especially important for its bioavailability and it is a key problem in the drug design process. In this paper, we present crystal structures of three animal serum albumin complexes: ovine, caprine, and leporine, with diclofenac, a popular non-steroidal anti-inflammatory drug that is used in therapy of chronic and acute pain. Details of diclofenac binding mode by the presented serum albumins are compared with analogous complexes of human and equine serum albumins. The analysis of the occupied binding pockets in crystal structures of the investigated serum albumins from different mammals shows that they have two common and a number of unique diclofenac binding sites. The most intriguing is the fact that the albumins from the described species are able to bind different numbers of molecules of this popular anti-inflammatory drug, but none of the binding sites overlap with ones in the human serum albumin.

The purpose of the present paper was to review the available evidence on intra-articular botulinum toxin (BTX) injection in the treatment of knee osteoarthritis and to compare it to other conservative treatment options. A systematic review of the literature was performed on the PubMed, Scopus, Cochrane Library, Web of Science, Pedro and Research Gate databases with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in the English language, and (3) published on indexed journals in the last 20 years (2001-2021) dealing with the use of BTX intra-articular injection for the treatment of knee OA. The risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs. Nine studies involving 811 patients in total were included. Patients in the control groups received different treatments: conventional physiotherapy, hyaluronic acid injection or prolotherapy or a combination thereof in 5 studies, steroid infiltrative therapy (triamcinolone) in 1 study, placebo in 2, and local anesthetic treatment in 1 study. Looking at the quality of the available literature, two of the included studies reached "Good quality" standard, three were ranked as "Fair", and the rest were considered "Poor". No major complications or serious adverse events were reported following intra-articular BTX, which provided encouraging pain relief, improved motor function, and quality of life. Based on the available data, no clear indication emerged from the comparison of BTX with other established treatments for knee OA. The analysis of the available RCTs on BTX intra-articular injection for the treatment of knee OA revealed modest methodological quality. However, based on the data retrieved, botulinum toxin has been proven to provide good short-term outcomes, especially in patients with pain sensitization, by modulating neurotransmitter release, peripheral nociceptive transduction, and acting on the control of chronic pain from central sensitization.