Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions.

Background: Allograft failure after kidney transplantation remains common despite improving long-term outcomes and persistent organ scarcity. We aimed to develop and internally validate a perioperative risk model for kidney allograft failure within 2 years of transplantation. Methods: We conducted a single-center retrospective cohort study using the Medical Informatics Operating Room Vitals and Events Repository. Adult patients (≥18 years) undergoing kidney transplantation between January 2018 and July 2023 with at least 2 years of follow-up were included. The primary outcome was allograft failure within 2 years, defined as return to dialysis, pre-emptive re-transplantation, or death. Candidate predictors included demographic characteristics, comorbidities, preoperative laboratory values, and intraoperative variables. After univariate screening and variable selection with LASSO-penalized regression, we estimated relative risks using modified Poisson regression and assessed internal validity with 200 bootstrap resamples. Results: Among 319 recipients, 53 (16.6%) experienced early allograft failure. In the final multivariable model, obesity (relative risk [RR] 4.76; bootstrap 95% CI 2.88–9.31) and thrombocytopenia (RR 1.96; bootstrap 95% CI 1.18–3.38) were independently associated with increased risk. Anemia (RR 0.22; bootstrap 95% CI 0.13–0.37), preoperative clonidine use (RR 0.33; bootstrap 95% CI 0.00–0.85), and female sex (RR 0.55; bootstrap 95% CI 0.26–0.83) were associated with reduced risk. Model performance was modest (pseudo-R² 0.21) but identified clinically distinct risk strata. Conclusions: A five-variable perioperative model based on obesity, thrombocytopenia, anemia, preoperative clonidine use, and female sex identified kidney transplant recipients at differing risk of allograft failure within 2 years. These associations highlight potentially modifiable targets that warrant further study and external validation before clinical use.

Objective: To evaluate the relationship between the patient’s reported level of pre-operative anxiety, the anaesthesiologist’s assessment of the patients’ anxiety level and the administration of anxiolytic premedication in the immediate pre-operative period. Methods: Patients' pre-operative anxiety level was self-assessed using a simple visual analog scale (0 = no anxiety to 10 = severe anxiety) in the pre-operative holding area. The anaesthesiologist independently visually assessed the patient’s level of anxiety on a similar 0 to 10 anxiety rating scale at the time of their pre-operative interview. Immediately after this, the anaesthesiologist decided whether to administer an anxiolytic medication prior to the patient entering the operating room. Results: Based on the anxiety scores reported by patients on the numeric analog scale, 58% (n=171) reported no-to-low levels of anxiety (scores ≤3) and 42% (n=122) reported moderate-to-high levels of anxiety (scores ≥4). According to the observational assessment by the anaesthesiologists, 70% of the patients were assigned an anxiety score ≤3 and 30% were assigned an anxiety score ≥4. Overall, 188 out of the 293 patients (64%) received a parenteral anxiolytic premedication. However, only 50% (61/122) of the patients reporting moderate-to-high levels of anxiety received an anxiolytic medication prior to entering the operating room. Surprisingly, 74% (127/171) of the patients reporting little or no anxiety were administered an anxiolytic drug. Interestingly, there was no significant difference in the average anxiety scores of patients who did or did not receive anxiolytic premedication (3.6±2.6 vs. 3.0±2.2, p= 0.11). Conclusions: These data suggest there is poor correlation between the patient’s reported level of pre-operative anxiety and the administration of anxiolytic medication. A more targeted approach to administering anxiolytic premedication based on the patient’s self-reported anxiety level in the pre-operative holding area would lead to more rationale use of anxiolytic medication prior to the patient entering the operating room.

Background and Clinical Significance: Sickle cell vaso-occlusive crisis (VOC) may present with severe refractory pain that is difficult to control despite guideline-directed multimodal therapy and high-dose opioids. Case Presentation: We report an adult with VOC and severe, opioid-refractory anterior thigh and leg pain who was treated with bilateral, ultrasound-guided continuous femoral nerve catheters (0.5% bupivacaine bolus per side followed by infusion of 0.2% ropivacaine at 5 mL/h each). Twenty-four-hour opioid use decreased by 76% from 44 mg intravenous hydromorphone (880 MME) before block placement to 10.4 mg (208 MME) after catheter initiation. Pain scores declined significantly from 10/10 to 3/10, facilitating mobilization and expediting discharge of the patient. No local anesthetic systemic toxicity occurred, and transient quadriceps weakness was managed with fall-risk precautions. IRB approval for this case report was waived per our institution policy. Conclusions: In select adults with VOC and predominant anterior thigh/leg pain, bilateral continuous femoral nerve catheters may provide rapid analgesia and substantial opioid-sparing benefits as part of multidisciplinary care. These findings are hypothesis-generating and support prospective evaluation of continuous peripheral nerve block strategies in VOC.