Implementation and outcomes of a statewide TBI screening program for underserved populations.

The purpose of this paper is to describe the implementation and outcomes of a unique traumatic brain injury (TBI) screening initiative serving the community, with a focus on underserved populations. Idaho's definition of underserved populations includes people living in rural/frontier areas, people experiencing homelessness or intimate partner violence, people with co-occurring disorders, and people with cultural and/or linguistically diverse backgrounds. The goals of screenings are to help participants gain awareness about the likelihood of having experienced a TBI, bridge the gap in TBI reporting, and provide needed support to underserved populations in a rural state. Our work represents a cross-sectional study. Beginning in 2014, TBI screenings were conducted by the Institute of Rural Health within a public health university with several internal and external partners, as well as grant funding for work. Trained interprofessional health students and/or members of the Institute of Rural Health performed TBI screenings using the Ohio State University TBI Identification Method-Interview Form. Those who screened as likely experiencing a TBI received resources for care and follow-up telephone calls. Data were collected on the number of individuals screened and their results and reported using descriptive statistics. From 2014 to 2022, a total of 1333 individuals were screened at 23 different community events across Idaho. Over 30% of screened individuals reported a history of head or neck injury, primarily due to falls and being hit by objects. The majority of identified cases of TBI were characterized by no loss of consciousness or <30 min of unconsciousness. Screenings targeting underserved populations showed higher TBI prevalence. Targeting underserved populations proved valuable in identifying TBI cases. The collaborative and interprofessional approach of this screening is unique and highlights the potential to address complex health issues effectively. These findings offer valuable insights for others implementing TBI screening programs in community settings.

Flourishing and the Prioritization of Workplace Elements in General Surgery Residents.

INTRODUCTION: To explore and begin to operationalize workplace elements that influence general surgery (GS) resident wellbeing. Tailoring workplace wellbeing interventions is critical to their success. Occupational science has revealed that a person-centered approach to identifying positive and negative workplace influences can inform tailoring while accounting for individual differences. To our knowledge, this approach has not been applied to the surgical training environment. METHODS: A national sample of GS residents from 16 Accreditation Council for Graduate Medical Education training programs ranked the importance of workplace elements via an anonymous survey. Latent profile analysis was performed to identify shared patterns of workplace element prioritization and their relation to levels of flourishing, a measure of global wellbeing. RESULTS: GS trainee respondents (n = 300, 34% response rate - average for studies with this sample population) expressed a hierarchy of workplace element importance which differed by gender and race. "Skills to manage stress" and "a team you feel a part of" were prioritized higher by non-males than males. Residents of color and residents underrepresented in medicine, respectively, prioritized "recognition of work/effort" and "skills to manage stress" more than White and overrepresented in medicine residents. Flourishing prevalence varied by 40% with small differences in the specific profile of workplace element prioritization. CONCLUSIONS: Differences in prioritization of workplace elements reveal subtle but important differences that may guide the design of wellbeing interventions for different populations within surgery.

Impact of local anesthesia block on pain medication use and length of hospital stay in elderly indigenous patients in Alaska hospitalized for fragility fracture.

Introduction: Fragility fractures (low-energy, minimal-trauma fractures) are common in the aging population and can lead to decreased function, increased mortality, and long-lasting pain. Although opioids are helpful in reducing acute postoperative pain, they present risks that may lead to increased morbidity and mortality. Materials and Methods: This was a retrospective review of medical records of all Alaska Native and American Indian people older than 50 years, who received surgery for hip fracture repair between January 2018 and June 2019 (n = 128). Results: We found that receipt of a peripheral nerve block (PNB) is a predictor for decreased length of hospital stay. However, receipt of PNB did not predict a reduction in postoperative morphine milligram equivalents opioid doses. Discussion: Further study is required to determine whether one PNB method is superior to others based on individual-level characteristics.

A translation control module coordinates germline stem cell differentiation with ribosome biogenesis during Drosophila oogenesis.

Ribosomal defects perturb stem cell differentiation, and this is the cause of ribosomopathies. How ribosome levels control stem cell differentiation is not fully known. Here, we discover that three DExD/H-box proteins govern ribosome biogenesis (RiBi) and Drosophila oogenesis. Loss of these DExD/H-box proteins, which we name Aramis, Athos, and Porthos, aberrantly stabilizes p53, arrests the cell cycle, and stalls germline stem cell (GSC) differentiation. Aramis controls cell-cycle progression by regulating translation of mRNAs that contain a terminal oligo pyrimidine (TOP) motif in their 5' UTRs. We find that TOP motifs confer sensitivity to ribosome levels that are mediated by La-related protein (Larp). One such TOP-containing mRNA codes for novel nucleolar protein 1 (Non1), a conserved p53 destabilizing protein. Upon a sufficient ribosome concentration, Non1 is expressed, and it promotes GSC cell-cycle progression via p53 degradation. Thus, a previously unappreciated TOP motif in Drosophila responds to reduced RiBi to co-regulate the translation of ribosomal proteins and a p53 repressor, coupling RiBi to GSC differentiation.

Direct patient care services by community and ambulatory care pharmacists in Idaho.

Background Pharmacists are one of the most accessible but unoptimized healthcare providers in the community. They are medication experts and have authority to independently prescribe in Idaho. Through the provision of direct patient care services (i.e., those distinct from traditional prescription dispensing functions), pharmacists have a greater opportunity to impact chronic disease prevention and management across the state. This can be done by filling gaps in community care (e.g., prescribing recommended therapy) and directly managing and preventing chronic diseases. However, current practices surrounding pharmacist-provided direct patient care services are unknown. Objective To characterize direct patient care services provided by Idaho community and ambulatory care pharmacists as well as to assess individual pharmacists' and their work sites' capacity and barriers in providing and expanding services. Setting Community and ambulatory care pharmacists' work sites in Idaho. Method We administered a cross-sectional, electronic, 20-min survey to Idaho community and ambulatory care pharmacists. Main outcome measure The survey focused on collecting data on current practices, capacity, and barriers related to pharmacist-provided direct patient care services. Results The survey was completed by 280 eligible community and ambulatory care pharmacists with the majority of respondents (n = 250) offering pharmacist-provided direct patient care services. Pharmacists most often prescribed therapy for tobacco cessation (nicotine replacement, bupropion, varenicline), naloxone, and devices for patients with diabetes. Top barriers to individual pharmacists providing services were dispensing load and workload while top barriers to work sites (e.g., environment) were reimbursement/billing, number of available staff, and workflow. Conclusion Idaho community and ambulatory care pharmacists currently offer direct patient care services to patients across the state, but face barriers in providing and increasing services offered.

Bitter taste receptors are expressed in human epithelial ovarian and prostate cancers cells and noscapine stimulation impacts cell survival.

Bitter taste receptors (Tas2Rs) are a subfamily of G-protein coupled receptors expressed not only in the oral cavity but also in several extra-oral tissues and disease states. Several natural bitter compounds from plants, such as bitter melon extract and noscapine, have displayed anti-cancer effects against various cancer types. In this study, we examined the prevalence of Tas2R subtype expression in several epithelial ovarian or prostate cancer cell lines, and the functionality of Tas2R14 was determined. qPCR analysis of five TAS2Rs demonstrated that mRNA expression often varies greatly in cancer cells in comparison to normal tissue. Using receptor-specific siRNAs, we also demonstrated that noscapine stimulation of ovarian cancer cells increased apoptosis in ovarian cancer cells in a receptor-dependent, but ROS-independent manner. This study furthers our understanding of the function of Tas2Rs in ovarian cancer by demonstrating that their activation has an impact on cell survival.

External validation of three risk stratification rules in patients presenting with pulmonary embolism and cancer.

Numerous risk stratification rules exist to predict post-pulmonary embolism (PE) mortality; however, few were designed for use in cancer patients. In the EPIPHANY registry, adapted versions of common rules (the Hestia criteria, Pulmonary Embolism Severity Index [PESI], and simplified PESI [sPESI]) displayed high sensitivity for prognosticating mortality in PE patients with cancer. These adapted rules have yet to be externally validated. Therefore, we sought to evaluate the performance of an adapted Hestia criteria, PESI, and sPESI for predicting 30-day post-PE mortality in patients with cancer. We identified consecutive, adults presenting with objectively confirmed PE and cancer to our institution (November 2010 to January 2014). The proportion of patients categorized as low or high risk by these three risk stratification rules was calculated, and each rule's accuracy for predicting 30-day all-cause mortality was determined. Of the 124 patients with PE and active cancer identified, 25 (20%) experienced mortality at 30 days. The adapted Hestia criteria categorized 23 (19%) patients as low risk, while exhibiting a sensitivity of 88% (95% confidence interval [CI] = 68-97%), a negative predictive value NPV of 87% (95% CI = 65-97%), and a specificity of 20% (95% CI = 13-30%). A total of 38 (31%) and 30 (24%) patients were low risk by the adapted PESI and sPESI, with both displaying sensitivities of 92% and NPVs > 93%. Specificities were 36% (95% CI = 27-47%) and 28% (95% CI = 20-38%) for PESI and sPESI. In our external validation, the adapted Hestia, PESI, and sPESI demonstrated high sensitivity but low specificity for 30-day PE mortality in patients with cancer. Larger, prospective trials are needed to optimize strategies for risk stratification in this population.

Cost-utility of empagliflozin in patients with type 2 diabetes at high cardiovascular risk.

AIMS: In the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG) trial, empagliflozin reduced cardiovascular and all-cause mortality in type 2 diabetes (T2D) patients at high cardiovascular risk. We sought to estimate the cost-effectiveness of empagliflozin versus standard treatment for the prevention of cardiovascular morbidity and mortality in patients with T2D. METHODS: A Markov model was developed to assess the cost-effectiveness of empagliflozin (versus standard treatment) for the prevention of cardiovascular morbidity and mortality in patients with T2D using a 3-month cycle length and a lifetime horizon. Data sources included the EMPA-REG randomized clinical trial and other published epidemiological studies. Outcomes included treatment costs (in 2016 US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analysis (PSA) was performed to test the robustness of conclusions. RESULTS: Empagliflozin use resulted in higher total lifetime treatment costs ($371,450 versus $272,966) but yielded greater QALYs (10.712 vs. 9.419) compared to standard treatment. This corresponded to an ICER of $76,167 per QALY gained. PSA suggested empagliflozin would be cost-effective in 96% of 10,000 iterations assuming a willingness-to-pay threshold of $100,000 per QALY gained. CONCLUSION: Empagliflozin may be cost-effective compared to standard treatment in T2D patients at high cardiovascular risk.

External Validation of Generic and Cancer-Specific Risk Stratification Tools in Patients With Pulmonary Embolism and Active Cancer.

Background: Numerous risk stratification tools exist to predict early post-pulmonary embolism (PE) mortality; however, few were specifically designed for use in patients with cancer. This study sought to evaluate the performance of 3 cancer-specific (RIETE, POMPE-C, and Font criteria) and 3 generic (Hestia, Pulmonary Embolism Severity Index [PESI], and Geneva prognostic score [GPS]) risk stratification tools for predicting 30-day post-PE mortality in patients with active cancer. Methods: We identified consecutive, adult, objectively confirmed patients with PE and active cancer presenting to our institution from November 2010 to January 2014. We calculated the proportion of patients categorized as low or high risk by each of the 6 risk stratification tools and determined each tools' accuracy for predicting 30-day all-cause mortality. Results: A total of 124 patients with PE and active cancer were included (mean age, 66.2 years; 46.0% with concurrent deep vein thrombosis; 49.2% with metastatic disease; and 46.8%, 16.9%, and 11.3% receiving chemotherapy, radiation, or both, respectively). Mortality at 30 days occurred in 25 patients (20.2%). The cancer-specific tools (POMPE-C, RIETE, and Font criteria) categorized between 32% and 43% of patients as low risk and displayed sensitivities and specificities of 88.0% to 96.0% and 38.4% to 52.5%, respectively. The generic PESI and Hestia tools had sensitivities >96.0%, but classified <19% of patients as low risk; specificity of these tools were low (PESI, 6.1%; Hestia, 23.2%). Although the final noncancer tool, GPS, classified 43.5% of patients as low risk, it did so with a sensitivity of 52.0% and specificity of 42.4%. Conclusions: When risk-stratifying PE in patients with active cancer, cancer-specific tools appeared to exhibit better prognostic accuracy than their generic counterparts. POMPE-C, RIETE, and the Font criteria identified a substantially greater proportion of patients with PE likely to survive to 30 days with comparable sensitivity to the generic tools.

Observation management of pulmonary embolism and agreement with claims-based and clinical risk stratification criteria in United States patients: a retrospective analysis.

BACKGROUND: Guidelines suggest observation stays are appropriate for pulmonary embolism (PE) patients at low-risk for early mortality. We sought to assess agreement between United States (US) observation management of PE and claims-based and clinical risk stratification criteria. METHODS: Using US Premier data from 11/2012 to 3/2015, we identified adult observation stay patients with a primary diagnosis of PE, ≥1 PE diagnostic test claim and evidence of PE treatment. The proportion of patients at high-risk was assessed using the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) equation and high-risk characteristics (age > 80 years, heart failure, chronic lung disease, renal or liver disease, high-risk for bleeding, cancer or need for thrombolysis/embolectomy). RESULTS: We identified 1633 PE patients managed through an observation stay. Despite their observation status, IMPACT classified 46.4% as high-risk for early mortality and 33.3% had ≥1 high-risk characteristic. Co-morbid heart failure, renal or liver disease, high-risk for major bleeding, cancer and hemodynamic instability were low (each <4.5%), but 7.8% were >80 years-of-age and 19.4% had chronic lung disease. CONCLUSION: Many PE patients selected for management in observation stay units appeared to have clinical characteristics suggestive of higher-risk for mortality based upon published claims-based and clinical risk stratification criteria.

Novel Use of Ranolazine as an Antiarrhythmic Agent in Atrial Fibrillation.

OBJECTIVE: To review the limitations of current antiarrhythmic drugs in atrial fibrillation (AF) and discuss the rationale and clinical trials supporting the use of ranolazine in AF. DATA SOURCES: MEDLINE was searched from 1980 to September 2016 using the terms ranolazine, atrial fibrillation, coronary artery bypass grafting, and valve surgery. STUDY SELECTION AND DATA EXTRACTION: English-language studies and reviews assessing antiarrhythmic drugs, including ranolazine, were incorporated. DATA SYNTHESIS: The use of ranolazine monotherapy has been evaluated in 2 clinical trials. In the RAFFAELLO trial, higher doses of ranolazine showed a trend toward lower AF recurrence versus placebo ( P = 0.053), but further evidence is needed to support its use as a sole therapeutic agent. Ranolazine has shown utility in a limited number of studies as an adjunctive agent, which is critical for those in whom standard therapy is inadequate or the adverse event profile precludes optimized standard therapy. In the HARMONY trial, ranolazine 750 mg and dronedarone 225 mg twice daily reduced the AF burden by 59.1% from baseline ( P = 0.008 vs placebo). In a trial by Koskinas and colleagues, patients receiving ranolazine 1500 mg once and intravenous amiodarone had a higher conversion rate than those receiving amiodarone alone ( P = 0.024). There are also promising studies for the prevention and treatment of post-cardiothoracic surgery AF, which require further investigation. CONCLUSIONS: Ranolazine's pharmacological properties and available evidence suggest potential for its use in AF.

Cost-Effectiveness of High-Dose Edoxaban Compared with Adjusted-Dose Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation Patients.

OBJECTIVE: To estimate the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of high-dose edoxaban compared with adjusted-dose warfarin in patients at risk for stroke who have nonvalvular atrial fibrillation (NVAF) and a creatinine clearance (Clcr ) of 15-95 ml/minute. METHODS: A Markov model was created to compare the cost-effectiveness of high-dose edoxaban and adjusted-dose warfarin in patients with a Clcr of 15-95 ml/minute. The model was performed from a U.S. societal perspective and assumed patients initiated therapy at 70 years of age, had a mean CHADS2 (congestive heart failure, hypertension, age 75 or older, diabetes, stroke) score of 3, and no contraindications to anticoagulation. The model assumed a cycle length of 1 month and a lifetime horizon (maximum of 30 years/360 cycles). Data sources included renal subgroup analysis of the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation (ENGAGE-AF) trial and other published studies. Outcomes included lifetime costs (2014 US$), QALYs, and incremental cost-effectiveness ratios. The robustness of the model's conclusions was tested using one-way and 10,000-iteration probabilistic sensitivity analysis (PSA). RESULTS: Patients treated with high-dose edoxaban lived an average of 10.50 QALYs at a lifetime treatment cost of $99,833 compared with 10.11 QALYs and $123,516 for those treated with adjusted-dose warfarin. The model's conclusions were found to be robust upon one-way sensitivity analyses. PSA suggested high-dose edoxaban was economically dominant compared with adjusted-dose warfarin in more than 99% of the 10,000 iterations run. CONCLUSIONS: High-dose edoxaban appears to be an economically dominant strategy when compared with adjusted-dose warfarin for the prevention of stroke in NVAF patients with a Clcr of 15-95 ml/minute and an appreciable risk of stroke.

A Review of New Pharmacologic Treatments for Patients With Chronic Heart Failure With Reduced Ejection Fraction.

Heart failure (HF) impacts an estimated 5.7 million Americans, and its prevalence is projected to increase to more than 8 million Americans in the next 15 years. Key clinical trials have established an evidence-based foundation for treatment of heart failure with reduced ejection fraction (HFrEF). Ivabradine and sacubitril/valsartan, which inhibit the f-channel and the angiotensin receptor and neprilysin, respectively, were recently approved by the Food and Drug Administration for HFrEF. In systolic heart failure, treatment with the If inhibitor ivabradine significantly reduced the combined endpoint of cardiovascular mortality or heart failure hospital admission vs placebo (P < .05). In the Prospective Comparison of angiotensin receptor-neprilysin inhibitor (ARNI) with angiotensin-converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure trial, sacubitril/valsartan significantly reduced the combined endpoint of cardiovascular death or heart failure hospitalization vs enalapril (P < .001). The place of therapy with ivabradine and sacubitril/valsartan is defined by these trials and their interplay with guideline-directed medical therapy. Ivabradine and sacubitril/valsartan increase pharmacotherapy options for the treatment of HFrEF but are not yet first-line agents. Clinical application will be better defined in the coming years as practitioners increase their familiarity with ivabradine and sacubitril/valsartan.

Enzymatically activated near infrared nanoprobes based on amphiphilic block copolymers for optical detection of cancer.

BACKGROUND AND OBJECTIVE: Nanotechnology offers the possibility of creating multi-functional structures that can provide solutions for biomedical problems. The nanoprobes herein described are an example of such structures, where nano-scaled particles have been designed to provide high specificity and contrast potential for optical detection of cancer. Specifically, enzymatically activated fluorescent nanoprobes (EANPs) were synthesized as cancer-specific contrast agents for optical imaging. STUDY DESIGN/MATERIALS AND METHODS: EANPs were prepared by nanoprecipitation of blends of poly(lactic acid)-b-poly(ethylene glycol) and poly(lactic-co-glycolic acid)-b-poly(l-lysine). The lysine moieties were then covalently decorated with the near infrared (NIR) fluorescent molecule AlexaFluor-750 (AF750). Close proximity of the fluorescent molecules to each other resulted in fluorescence quenching, which was reversed by enzymatically mediated cleavage of poly(l-lysine) chains. EANPs were characterized by dynamic light scattering and electron microscopy. Enzymatic development of fluorescence was studied in vitro by fluorescence spectroscopy. Biocompatibility and contrast potential of EANPs were studied in cancerous and noncancerous cells. The potential of the nanoprobes as contrast agents for NIR fluorescence imaging was studied in tissue phantoms. RESULTS: Spherical EANPs of ∼100 nm were synthesized via nanoprecipitation of polymer blends. Fluorescence activation of EANPs by treatment with a model protease was demonstrated with up to 15-fold optical signal enhancement within 120 minutes. Studies with MDA-MB-231 breast cancer cells demonstrated the cytocompatibility of EANPs, as well as enhanced fluorescence associated with enzymatic activation. Imaging studies in tissue phantoms confirmed the ability of a simple imaging system based on a laser source and CCD camera to image dilute suspensions of the nanoprobe at depths of up to 4 mm, as well as up to a 13-fold signal-to-background ratio for enzymatically activated EANPs compared to un-activated EANPs at the same concentration. CONCLUSION: Nanoprecipitation of copolymer blends containing poly(l-lysine) was utilized as a method for preparation of highly functional nanoprobes with high potential as contrast agents for fluorescence based imaging of cancer. Lasers Surg. Med. 47:579-594, 2015. © 2015 Wiley Periodicals, Inc.

Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies.

Olfactomedin (OLF) domains are found within extracellular, multidomain proteins in numerous tissues of multicellular organisms. Even though these proteins have been implicated in human disorders ranging from cancers to attention deficit disorder to glaucoma, little is known about their structure(s) and function(s). Here we biophysically, biochemically, and structurally characterize OLF domains from H. sapiens olfactomedin-1 (npoh-OLF, also called noelin, pancortin, OLFM1, and hOlfA), and M. musculus gliomedin (glio-OLF, also called collomin, collmin, and CRG-L2), and compare them with available structures of myocilin (myoc-OLF) recently reported by us and R. norvegicus glio-OLF and M. musculus latrophilin-3 (lat3-OLF) by others. Although the five-bladed ß-propeller architecture remains unchanged, numerous physicochemical characteristics differ among these OLF domains. First, npoh-OLF and glio-OLF exhibit prominent, yet distinct, positive surface charges and copurify with polynucleotides. Second, whereas npoh-OLF and myoc-OLF exhibit thermal stabilities typical of human proteins near 55°C, and most myoc-OLF variants are destabilized and highly prone to aggregation, glio-OLF is nearly 20°C more stable and significantly more resistant to chemical denaturation. Phylogenetically, glio-OLF is most similar to primitive OLFs, and structurally, glio-OLF is missing distinguishing features seen in OLFs such as the disulfide bond formed by N- and C- terminal cysteines, the sequestered Ca2+ ion within the propeller central hydrophilic cavity, and a key loop-stabilizing cation-π interaction on the top face of npoh-OLF and myoc-OLF. While deciphering the explicit biological functions, ligands, and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, we used structural insights gained here to generate a new antibody selective for myoc-OLF over npoh-OLF and glio-OLF as a first step in overcoming the impasse in detailed functional characterization of these biomedically important protein domains.

Structural basis for misfolding in myocilin-associated glaucoma.

Olfactomedin (OLF) domain-containing proteins play roles in fundamental cellular processes and have been implicated in disorders ranging from glaucoma, cancers and inflammatory bowel disorder, to attention deficit disorder and childhood obesity. We solved crystal structures of the OLF domain of myocilin (myoc-OLF), the best studied such domain to date. Mutations in myoc-OLF are causative in the autosomal dominant inherited form of the prevalent ocular disorder glaucoma. The structures reveal a new addition to the small family of five-bladed ß-propellers. Propellers are most well known for their ability to act as hubs for protein-protein interactions, a function that seems most likely for myoc-OLF, but they can also act as enzymes. A calcium ion, sodium ion and glycerol molecule were identified within a central hydrophilic cavity that is accessible via movements of surface loop residues. By mapping familial glaucoma-associated lesions onto the myoc-OLF structure, three regions sensitive to aggregation have been identified, with direct applicability to differentiating between neutral and disease-causing non-synonymous mutations documented in the human population worldwide. Evolutionary analysis mapped onto the myoc-OLF structure reveals conserved and divergent regions for possible overlapping and distinctive functional protein-protein or protein-ligand interactions across the broader OLF domain family. While deciphering the specific normal biological functions, ligands and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, atomic detail structural knowledge of myoc-OLF is a valuable guide for understanding the implications of glaucoma-associated mutations and will help focus future studies of this biomedically important domain family.

Spontaneous behavioral responses in the orofacial region: a model of trigeminal pain in mouse.

OBJECTIVES: To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse. BACKGROUND: Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients, they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited, and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology. METHODS: C57BL/6 mice received either an injection of 0.9% saline solution or complete Freund's adjuvant into the right masseter muscle. Animals were video-recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hours, mice were euthanized and perfused, and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate to determine the nociceptive-specific nature of their behaviors. RESULTS: We characterized and quantified 3 distinct patterns of acute grooming behaviors: forepaw rubbing, lower lip skin/cheek rubbing against enclosure floor, and hindpaw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. Complete Freund's adjuvant-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after 2 hours. CONCLUSIONS: These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this common and challenging condition.