Accepted

Temporomandibular disorder (TMD) is a common condition that frequently transitions to chronic symptoms. Experimental pain models that mimic the symptoms of clinical TMD may be useful in understanding the mechanisms, and sex differences, present in this disorder. Here we aimed to comprehensively characterise the nature and time-course of pain, functional impairment and hyperalgesia induced by repeated intramuscular injection of nerve growth factor (NGF) into the masseter muscle, and to investigate sex differences in the NGF-induced pain experience.

The voltage-gated sodium NaV1.7 channel sets the threshold for electrogenesis. Mutations in the gene encoding human NaV1.7 () cause painful neuropathies or pain insensitivity. In dorsal root ganglion (DRG) neurons, activity and trafficking of NaV1.7 are regulated by the auxiliary collapsin response mediator protein 2 (CRMP2). Specifically, preventing addition of a small ubiquitin-like modifier (SUMO), by the E2 SUMO-conjugating enzyme Ubc9, at lysine-374 (K374) of CRMP2 reduces NaV1.7 channel trafficking and activity. We previously identified a small molecule, designated , that prevented CRMP2 SUMOylation by Ubc9 to reduce NaV1.7 surface expression and currents, leading to a reduction in spinal nociceptive transmission, and culminating in normalization of mechanical allodynia in models of neuropathic pain. In this study, we investigated whether NaV1.7 control via CRMP2-SUMOylation is conserved in nodose ganglion (NG) neurons. This study was motivated by our desire to develop as a safe, non-opioid substitute for persistent pain, which led us to wonder how would impact NaV1.7 in NG neurons, which are responsible for driving the cough reflex. We found functioning NaV1.7 channels in NG neurons; however, they were resistant to downregulation via either CRMP2 knockdown or pharmacological inhibition of CRMP2 SUMOylation by CRMP2 SUMOylation and interaction with NaV1.7 was consered in NG neurons but the endocytic machinery was deficient in the endocytic adaptor protein Numb. Overexpression of Numb rescued CRMP2-dependent regulation on NaV1.7, rendering NG neurons sensitive to Altogether, these data point at the existence of cell-specific mechanisms regulating NaV1.7 trafficking.

Clinical production pressure is a significant problem for faculty of anesthesiology departments who seek to remain involved in research. Lack of protected time to dedicate to research and insufficient external funding add to this long-standing issue. Recent trends in funding to the departments of anesthesiology and their academic output validate these concerns. A 2022 study examining National Institutes of Health (NIH) grant recipients associated with anesthesiology departments across 10 years (2011-2020) outlines total awarded funds at $1,676,482,440, with most of the funds awarded to only 10 departments in the United States. Of note, the total 1-year NIH funding in 2021 for academic internal medicine departments was 3 times higher than the 10-year funding of anesthesiology departments. Additionally, American Board of Anesthesiology (ABA) diplomats represent a minority (37%) of the anesthesiology researchers obtaining grant funding, with a small number of faculty members receiving a prevalence of monies. Overall, the number of publications per academic anesthesiologist across the United States remains modest as does the impact of the scholarly work. Improving environments in which academic anesthesiologists thrive may be paramount to successful academic productivity. In fact, adding to the lack of academic time is the limited bandwidth of senior academic physicians to mentor and support aspiring physician scientists. Given then the challenges for individual departments and notable successes of specialty-specific collaborative efforts (eg Foundation for Anesthesia Education and Research [FAER]), additional pooled-resource approaches may be necessary to successfully support and develop clinician scientists. It is in this spirit that the leadership of , unified with the Association of University Anesthesiologists, aim to sponsor the Introduction to Clinical Research for Academic Anesthesiologists (ICRAA) Course. Directed toward early career academic anesthesiologists who wish to gain competency specifically in the fundamentals of clinical research and receive mentorship to develop an investigative project, the yearlong course will provide participants with the skills necessary to design research initiatives, ethically direct research teams, successfully communicate ideas with data analysts, and write and submit scientific articles. Additionally, the course, articulated in a series of interactive lectures, mentored activities, and workshops, will teach participants to review articles submitted for publication to medical journals and to critically appraise evidence in published research. It is our hope that this initiative will be of interest to junior faculty of academic anesthesiology departments nationally and internationally.

There are numerous strategies to combat postoperative analgesia and expedite recovery after total knee arthroplasty (TKA). The purpose of this study was to determine opioid consumption, length of stay, and functional outcomes after robotic versus standard TKA in the setting of various regional pain modalities.

Patients undergoing spinal surgery are at high risk of acute and persistent postoperative pain. Therefore, adequate pain relief is crucial. This systematic review aimed to provide answers about best-proven postoperative analgesic treatment for patients undergoing lumbar 1- or 2-level fusions for degenerative spine diseases. We performed a search in PubMed, Embase, and The Cochrane Library for randomized controlled trials. The primary outcome was opioid consumption after 24 hours postoperatively. We performed meta-analyses, trial sequential analyses, and Grading of Recommendations assessment to accommodate systematic errors. Forty-four randomized controlled trials were included with 2983 participants. Five subgroups emerged: nonsteroidal anti-inflammatory drugs (NSAIDs), epidural, ketamine, local infiltration analgesia, and intrathecal morphine. The results showed a significant reduction in opioid consumption for treatment with NSAID ( < 0.0008) and epidural ( < 0.0006) (predefined minimal clinical relevance of 10 mg). Concerning secondary outcomes, significant reductions in pain scores were detected after 6 hours at rest (NSAID [ < 0.0001] and intrathecal morphine [ < 0.0001]), 6 hours during mobilization (intrathecal morphine [ = 0.003]), 24 hours at rest (epidural [ < 0.00001] and ketamine [ < 0.00001]), and 24 hours during mobilization (intrathecal morphine [ = 0.03]). The effect of wound infiltration was nonsignificant. The quality of evidence was low to very low for most trials. The results from this systematic review showed that some analgesic interventions have the capability to reduce opioid consumption compared with control groups. However, because of the high risk of bias and low evidence, it was impossible to recommend a "gold standard" for the analgesic treatment after 1- or 2-level spinal fusion surgery.

A higher level of pain self-efficacy has been suggested as a predictor of a better outcome in patients with musculoskeletal disorders. The Pain Self-Efficacy Questionnaire (PSEQ) is one of the most frequently used patient-reported outcome measures for pain self-efficacy. The purpose of this study was to conduct a systematic review that would identify, appraise, and synthetize the psychometric properties of the PSEQ. Embase, MEDLINE, and CINAHL databases were searched for publications reporting on psychometric properties of the PSEQ in populations with musculoskeletal disorders. After applying selection criteria on identified citations, 28 studies (9853 participants) were included. The methodological quality as measured with the COSMIN risk of bias tool varied from to for most measurement properties. The results showed a weighted mean intraclass correlation coefficient of 0.86 (range: 0.75-0.93) for test-retest reliability for the original 10-item PSEQ and the minimal detectable change at 95% confidence interval was 11.52 out of 60 points. Effect size and standardized response mean values were 0.53 and 0.63, respectively, whereas the minimal clinically important difference ranged from 5.5 to 8.5 in patients with chronic low back pain. Internal consistency (Cronbach alpha) ranged from 0.79 to 0.95. The results also showed that the PSEQ has low to moderate correlations with measures of quality of life, disability, pain, pain interference, anxiety, depression, and catastrophizing. Finally, the PSEQ has been adapted and validated in 14 languages. Overall, the results demonstrate that the PSEQ has excellent validity, reliability, and responsiveness. Further high-quality studies are needed to determine responsiveness in populations other than chronic low back pain.