Pain Management Commons^™

Preclinical Perspectives On Disorders Of The Temporomandibular Joint: Tracing The Past, Navigating The Present, And Shaping The Future, John K Neubert, Kyle Allen, Tamara Alliston, Alejandro J Almarza, Kyriacos A Athanasiou, Basak Donertas-Ayaz, Bruna Balbino De Paula, Roxanne Bavarian, Nidhi Bhutani, Brian E Cairns, Robert M Caudle, Yang Chai, Jian-Fu Chen, Yong Chen, Glenn T Clark, Yenisel Cruz-Almeida, Alexandre F Dasilva, Paul L Durham, Airam Vivanco Estela, Millie Embree, Roger Fillingim, Fernando Guastaldi, Shruti Handa, Sunil D Kapila, David Keith, Keith L Kirkwood, Phillip Kramer, Katherine T Martucci, Niall P Murphy, Andrea G Nackley, Richard Ohrbach, Benedikt Sagl, Shad B Smith, Feng Tao, Beth Winkelstein, Hai Yao, Simon Young, Michael S Gold

Faculty, Staff and Student Publications

Temporomandibular disorders (TMDs) are complex conditions characterized by orofacial pain and dysfunction, affecting a significant portion of the population. TMDs may involve joint and/or muscle pain, dysfunction (e.g., noise, limited or altered jaw movements), or both, leading to a marked decrease in quality of life. Patients often experience functional limitations that hinder eating, speaking, and daily activities. Additionally, TMDs are frequently associated with psychological distress, including anxiety and depression, which further impacts overall well-being. Despite the profound individual and societal impact of TMDs, effective therapies remain elusive, partly due to deficiencies in translational research. A primary limitation in the TMD …

Baseline Predictors Of Responders To Auricular Point Acupressure In Chronic Low Back Pain, Nada Lukkahatai, Wanqi Chen, Jennifer Kawi, Hulin Wu, Claudia M Campbell, Johannes Thrul, Xinran Huang, Paul Christo, Constance M Johnson

Faculty, Staff and Student Publications

Background: Chronic low back pain (cLBP) is a major cause of disability, with varied patient responses to treatments. Auricular point acupressure (APA) has shown potential as a non-pharmacological intervention, but individual responses may differ significantly.

Objective: This study aimed to determine the predictability of baseline characteristics, including functional disability, symptom severity, and treatment expectancy, on clinically significant responses to APA in reducing pain and improving function.

Methods: A secondary analysis was performed using data from a randomized controlled trial with 263 cLBP patients. Participants were randomly assigned to targeted APA (T-APA), non-targeted APA (NT-APA), or to a control group. APA …

Co-Morbid Indomethacin-Responsive Headaches In A Woman In Her Late 60s With Paroxysmal Hemicrania And Hypnic Headache: A Case Report, Ashlyn Brown, Randolph W Evans, Claudia Carrizo, Mark Burish

Faculty, Staff and Student Publications

Paroxysmal hemicrania (PH) and hypnic headache (HH) are rare indomethacin-responsive headache syndromes. This case report details the new onset of both disorders in a woman in her late 60s. One headache type presented as severe pain centered on the right eyebrow, lasting 30 minutes, occurring more than 8 times daily, and associated with ipsilateral lacrimation and rhinorrhea. The second type was a right frontal severe pain, with onset at 4 a.m., occurring only during sleep, lasting 30 minutes, and with no associated factors. The patient's response to indomethacin for both headache types was confirmed through an unblinded ABAB study design: …

Artificial Intelligence And Machine Learning In Cancer Pain: A Systematic Review, Vivian Salama, Brandon Godinich, Yimin Geng, Laia Humbert-Vidan, Laura Maule, Kareem A Wahid, Mohamed A Naser, Renjie He, Abdallah S R Mohamed, Clifton D Fuller, Amy C Moreno

Faculty, Staff and Student Publications

Background/objectives: Pain is a challenging multifaceted symptom reported by most cancer patients. This systematic review aims to explore applications of artificial intelligence/machine learning (AI/ML) in predicting pain-related outcomes and pain management in cancer.

Methods: A comprehensive search of Ovid MEDLINE, EMBASE and Web of Science databases was conducted using terms: "Cancer," "Pain," "Pain Management," "Analgesics," "Artificial Intelligence," "Machine Learning," and "Neural Networks" published up to September 7, 2023. AI/ML models, their validation and performance were summarized. Quality assessment was conducted using PROBAST risk-of-bias andadherence to TRIPOD guidelines.

Results: Forty four studies from 2006 to 2023 were included. Nineteen studies used …

Methods For Pragmatic Randomized Clinical Trials Of Pain Therapies: Immpact Statement, David Hohenschurz-Schmidt, Dan Cherkin, Andrew S C Rice, Robert H Dworkin, Dennis C Turk, Michael P Mcdermott, Matthew J Bair, Lynn L Debar, Robert R Edwards, Scott R Evans, John T Farrar, Robert D Kerns, Michael C Rowbotham, Ajay D Wasan, Penney Cowan, Mckenzie Ferguson, Roy Freeman, Jennifer S Gewandter, Ian Gilron, Hanna Grol-Prokopczyk, Smriti Iyengar, Cornelia Kamp, Barbara I Karp, Bethea A Kleykamp, John D Loeser, Sean Mackey, Richard Malamut, Ewan Mcnicol, Kushang V Patel, Kenneth Schmader, Lee Simon, Deborah J Steiner, Christin Veasley, Jan Vollert

Faculty, Staff and Student Publications

Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the …

Disability In Cluster Headache Is More Than Attack Frequency – Results From And Validation Of The English Version Of The Cluster Headache Impact Questionnaire (Chiq), Katharina Kamm, Andreas Straube, Mark Burish, Ruth Ruscheweyh

Faculty, Staff and Student Publications

BACKGROUND: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire.

METHODS: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group.

RESULTS: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by …

Utilising Discriminant Function Analysis (Dfa) For Classifying Osteoarthritis (Oa) Patients And Volunteers Based On Biomarker Concentration, Laura Jane Coleman, John L Byrne, Stuart Edwards, Rosemary O'Hara

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of cartilage, causing pain, stiffness, and limited movement. Early diagnosis is crucial for effective management but remains challenging due to non-specific early symptoms. This study explores the application of Discriminant Function Analysis (DFA) to classify OA patients and healthy volunteers based on biomarker concentrations of Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α), and Myeloperoxidase (MPO). DFA was employed to analyse biomarker data from 86 participants (58 patients, 28 volunteers) to evaluate the discriminatory power of these biomarkers in predicting OA. Significant differences were observed in MPO and TNF-α levels between …

Dyadic Yoga For Head And Neck Cancer Patients Undergoing Chemoradiation And Their Family Caregivers, Kathrin Milbury, David I Rosenthal, Yisheng Li, An Thuy Ngo-Huang, Smitha Mallaiah, Sania Yousuf, Clifton D Fuller, Carol Lewis, Eduardo Bruera, Lorenzo Cohen

Faculty, Staff and Student Publications

Objectives: Concurrent chemoradiation to treat head and neck cancer (HNC) may result in debilitating toxicities. Targeted exercise such as yoga therapy may buffer against treatment-related sequelae; thus, this pilot RCT examined the feasibility and preliminary efficacy of a yoga intervention. Because family caregivers report low caregiving efficacy and elevated levels of distress, we included them in this trial as active study participants.

Methods: HNC patients and their caregivers were randomized to a 15-session dyadic yoga program or a waitlist control (WLC) group. Prior to randomization, patients completed standard symptom (MDASI-HN) and patients and caregivers completed quality of life (SF-36) assessments. …

Risk Factors For Pediatric Ischemic Stroke And Intracranial Hemorrhage: A National Electronic Health Record Based Study, Stuart Fraser, Samantha M Levy, Amee Moreno, Gen Zhu, Sean Savitz, Alicia Zha, Hulin Wu

Faculty, Staff and Student Publications

BACKGROUND: Stroke is an important cause of morbidity in pediatrics. Large studies are needed to better understand the epidemiology, pathogenesis and risk factors associated with pediatric stroke. Large administrative datasets can provide information on risk factors in perinatal and childhood stroke at low cost. The aim of this hypothesis-generating study was to use a large administrative dataset to assess for prevalence and odds-ratios of rare exposures associated with pediatric stroke.

METHODS: The data for patients aged 0-18 with a diagnosis of either ischemic stroke or intracranial hemorrhage were extracted from the Cerner Health Facts EMR Database from 2000 to 2018. …

Adapting And Evaluating A Theory-Driven, Non-Pharmacological Intervention To Self-Manage Pain, Jennifer Kawi, Chao Hsing Yeh, Lauren Grant, Johannes Thrul, Hulin Wu, Paul J Christo, Lorraine S Evangelista

Faculty, Staff and Student Publications

BACKGROUND: The existing literature has limited detail on theory-driven interventions, particularly in pain studies. We adapted Bandura's self-efficacy framework toward a theory-driven, non-pharmacological intervention using auricular point acupressure (APA) and evaluated participants' perceptions of this intervention on their pain self-management. APA is a non-invasive modality based on auricular acupuncture principles.

METHODS: We mapped our study intervention components according to Bandura's key sources of self-efficacy (performance accomplishments, vicarious experience, verbal persuasion, and emotional arousal) to facilitate the self-management of pain. Through a qualitative study design, we conducted virtual interviews at one and three months after a 4-week APA intervention among 23 …

Commentary On 2022 Guidelines On Clinical Trial Design In Cluster Headache And Further Suggestions, Ioana Medrea, Stewart J Tepper, Donliang Wang, Paul G Mathew, Mark Burish

Faculty, Staff and Student Publications

BACKGROUND: New guidelines for cluster headache clinical trials were recently published. We welcome these new guidelines and raise additional considerations in trial methodologies.

MAIN BODY: We present non-inferiority trials to overcome ethical issues with placebo use, and additionally discuss issues with trial recruitment.

CONCLUSIONS: We highlight some possible issues and solutions to be considered with the recently published cluster headache trial guidelines.

Patient And Dentist Perspectives On Collecting Patient Reported Outcomes After Painful Dental Procedures In The National Dental Pbrn, Elsbeth Kalenderian, Sayali Tungare, Urvi Mehta, Sharmeen Hamid, Rahma Mungia, Alfa-Ibrahim Yansane, David Holmes, Kim Funkhouser, Ana M Ibarra-Noriega, Janelle Urata, D Brad Rindal, Heiko Spallek, Joel White, Muhammad F Walji

Faculty, Staff and Student Publications

BACKGROUND: Dental Patient Reported Outcomes (PROs) relate to a dental patient's subjective experience of their oral health. How practitioners and patients value PROs influences their successful use in practice.

METHODS: Semi-structured interviews were conducted with 22 practitioners and 32 patients who provided feedback on using a mobile health (mHealth) platform to collect the pain experience after dental procedures. A themes analysis was conducted to identify implementation barriers and facilitators.

RESULTS: Five themes were uncovered: (1) Sense of Better Care. (2) Tailored Follow-up based on the dental procedure and patient's pain experience. (3) Effective Messaging and Alerts. (4) Usable Digital Platform. …

An Opioid-Minimizing Multimodal Pain Regimen Reduces Opioid Exposure And Pain In Trauma-Injured Patients At High Risk For Opioid Misuse: Secondary Analysis From The Mast Trial, Constanza De Dios, Robert Suchting, Charles Green, James M Klugh, John A Harvin, Heather E Webber, Joy M Schmitz, Scott D Lane, Jin H Yoon, Angela Heads, Kandice Motley, Angela Stotts

Faculty, Staff and Student Publications

BACKGROUND: Screening to identify patients at risk for opioid misuse after trauma is recommended but not commonly used to guide perioperative opioid management interventions. The Multimodal Analgesic Strategies for Trauma trial demonstrated that an opioid-minimizing multimodal pain regimen reduced opioid exposure in a heterogeneous trauma patient population. Here, we assess the efficacy of the Multimodal Analgesic Strategies for Trauma multimodal pain regimen in a critical patient subgroup who screened at high risk for opioid misuse.

METHODS: The Multimodal Analgesic Strategies for Trauma trial compared an opioid-minimizing multimodal pain regimen (oral acetaminophen, naproxen, gabapentin, lidocaine patch, as-needed opioid) against an original …

Benefits Of The Enhanced Recovery After Surgery (Eras) Pathway With Quadratus Lumborum Blocks For Minimally Invasive Gynecologic Surgery Patients: A Retrospective Cohort Study, Paul S Lee, Laurie L Brunette, Intira Sriprasert, Mohamed Eloustaz, Rasika Deshpande, Crystal Adams, Laila Muderspach, Lynda Roman, Shane Dickerson, Michael P Kim

Faculty, Staff and Student Publications

STUDY OBJECTIVE: This study aimed to determine the effect of the implementation of the Enhanced Recovery After Surgery (ERAS) protocol among patients receiving minimally invasive gynecologic surgery.

DESIGN AND SETTING: This retrospective cohort study was performed in a tertiary care hospital.

PATIENTS: A total of 328 females who underwent minimally invasive gynecologic surgeries requiring at least one overnight stay at Keck Hospital of University of Southern California (USC), California, USA, from 2016 to 2020 were included in this study.

INTERVENTIONS: The institutional ERAS protocol was implemented in late 2018. A total of 186 patients from 2016 to 2018 prior to …

Evaluating The Impact Of An Mhealth Platform For Managing Acute Postoperative Dental Pain: Randomized Controlled Trial, Bunmi Tokede, Alfa Yansane, Ana Ibarra-Noriega, Joanna Mullins, Kristen Simmons, Nicholas Skourtes, Urvi Mehta, Sayali Tungare, David Holmes, Joel White, Muhammad Walji, Elsbeth Kalenderian

Faculty, Staff and Student Publications

BACKGROUND: Postoperative dental pain is pervasive and can affect a patient's quality of life. Adopting a patient-centric approach to pain management involves having contemporaneous information about the patient's experience of pain and using it to personalize care.

OBJECTIVE: In this study, we evaluated the use of a mobile health (mHealth) platform to collect pain-related patient-reported outcomes over 7 days after the patients underwent pain-inducing dental procedures; we then relayed the information to the dentist and determined its impact on the patient's pain experience.

METHODS: The study used a cluster-randomized experimental study design with an intervention arm where patients were prompted …

Aibp Regulates Trpv1 Activation In Chemotherapy-Induced Peripheral Neuropathy By Controlling Lipid Raft Dynamics And Proximity To Tlr4 In Dorsal Root Ganglion Neurons, Juliana M Navia-Pelaez, Julia Borges Paes Lemes, Leonardo Gonzalez, Lauriane Delay, Luciano Dos Santos Aggum Capettini, Jenny W Lu, Gilson Gonçalves Dos Santos, Ann M Gregus, Patrick M Dougherty, Tony L Yaksh, Yury I Miller

Faculty, Staff and Student Publications

Nociceptive afferent signaling evoked by inflammation and nerve injury is mediated by the opening of ligand-gated and voltage-gated receptors or channels localized to cholesterol-rich lipid raft membrane domains. Dorsal root ganglion (DRG) nociceptors express high levels of toll-like receptor 4 (TLR4), which also localize to lipid rafts. Genetic deletion or pharmacologic blocking of TLR4 diminishes pain associated with chemotherapy-induced peripheral neuropathy (CIPN). In DRGs of mice with paclitaxel-induced CIPN, we analyzed DRG neuronal lipid rafts, expression of TLR4, activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), and TLR4-TRPV1 interaction. Using proximity ligation assay, flow cytometry, and …

One Immune System Plays Many Parts: The Dynamic Role Of The Immune System In Chronic Pain And Opioid Pharmacology, Sanam Mustafa, Juliana E Bajic, Benjamin Barry, Samuel Evans, Kariel R Siemens, Mark R Hutchinson, Peter M Grace

Faculty, Staff and Student Publications

The transition from acute to chronic pain is an ongoing major problem for individuals, society and healthcare systems around the world. It is clear chronic pain is a complex multidimensional biological challenge plagued with difficulties in pain management, specifically opioid use. In recent years the role of the immune system in chronic pain and opioid pharmacology has come to the forefront. As a highly dynamic and versatile network of cells, tissues and organs, the immune system is perfectly positioned at the microscale level to alter nociception and drive structural adaptations that underpin chronic pain and opioid use. In this review, …

Biological Correlates Of The Effects Of Auricular Point Acupressure On Pain, Chao Hsing Yeh, Nada Lukkahatai, Xinran Huang, Hulin Wu, Hongyu Wang, Jingyu Zhang, Xinyi Sun, Thomas J Smith

Faculty, Staff and Student Publications

BACKGROUND: To identify candidate inflammatory biomarkers for the underlying mechanism of auricular point acupressure (APA) on pain relief and examine the correlations among pain intensity, interference, and inflammatory biomarkers.

DESIGN: This is a secondary data analysis.

METHODS: Data on inflammatory biomarkers collected via blood samples and patient self-reported pain intensity and interference from three pilot studies (chronic low back pain, n = 61; arthralgia related to aromatase inhibitors, n = 20; and chemotherapy-induced neuropathy, n = 15) were integrated and analyzed. This paper reports the results based on within-subject treatment effects (change in scores from pre- to post-APA intervention) for …

Pain Experience And Sensory Changes In Astronauts During And After Short-Lasting Commercial Spaceflight: A Proof-Of-Concept Study, Andrea K Sauer, Marie Vigouroux, Patrick M Dougherty, Juan Pablo Cata, Pablo M Ingelmo

Faculty, Staff and Student Publications

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. …

Pain Experience And Sensory Changes In Astronauts During And After Short-Lasting Commercial Spaceflight: A Proof-Of-Concept Study, Andrea K Sauer, Marie Vigouroux, Patrick M Dougherty, Juan Pablo Cata, Pablo M Ingelmo

Faculty, Staff and Student Publications

Space travel has been associated with musculoskeletal pain, yet little is known about the nociceptive changes and pain experience during spaceflight. This preliminary study aims to investigate the pain experience and sensory alterations in astronauts following a 17-day mission to the International Space Station (ISS) on Axiom Space's AX-1 commercial space flight. Two participants were enrolled, and data were collected pre-flight, in-flight, post-flight, and three-month post-flight. Validated pain questionnaires assessed anxiety, catastrophizing, impact on physical and mental health, disability, and overall pain experience. Qualitative interviews were conducted post-landing and conditioned pain modulation (CPM) and quantitative sensory testing (QST) were performed. …

Hdac2 In Primary Sensory Neurons Constitutively Restrains Chronic Pain By Repressing Α2Δ-1 Expression And Associated Nmda Receptor Activity, Jixiang Zhang, Shao-Rui Chen, Meng-Hua Zhou, Daozhong Jin, Hong Chen, Li Wang, Ronald A Depinho, Hui-Lin Pan

Faculty, Staff and Student Publications

α2δ-1 (encoded by the Cacna2d1 gene) is a newly discovered NMDA receptor-interacting protein and is the therapeutic target of gabapentinoids (e.g., gabapentin and pregabalin) frequently used for treating patients with neuropathic pain. Nerve injury causes sustained α2δ-1 upregulation in the dorsal root ganglion (DRG), which promotes NMDA receptor synaptic trafficking and activation in the spinal dorsal horn, a hallmark of chronic neuropathic pain. However, little is known about how nerve injury initiates and maintains the high expression level of α2δ-1 to sustain chronic pain. Here, we show that nerve injury caused histone hyperacetylation and diminished enrichment of histone deacetylase-2 (HDAC2), …

Preconditioning By Voluntary Wheel Running Attenuates Later Neuropathic Pain Via Nuclear Factor E2-Related Factor 2 Antioxidant Signaling In Rats, Suzanne M Green-Fulgham, Michael E Harland, Jayson B Ball, Jiahe Li, Michael J Lacagnina, Heather D'Angelo, Renee A Dreher, Kendal F Willcox, Sabina A Lorca, Andrew J Kwilasz, Steven F Maier, Linda R Watkins, Peter M Grace

Faculty, Staff and Student Publications

Animal and human studies have shown that exercise prior to nerve injury prevents later chronic pain, but the mechanisms of such preconditioning remain elusive. Given that exercise acutely increases the formation of free radicals, triggering antioxidant compensation, we hypothesized that voluntary running preconditioning would attenuate neuropathic pain by supporting redox homeostasis after sciatic nerve injury in male and female rats. We show that 6 weeks of voluntary wheel running suppresses neuropathic pain development induced by chronic constriction injury across both sexes. This attenuation was associated with reduced nitrotyrosine immunoreactivity-a marker for peroxynitrite-at the sciatic nerve injury site. Our data suggest …

Fadu Head And Neck Squamous Cell Carcinoma Induces Hyperexcitability Of Primary Sensory Neurons In An In Vitro Coculture Model, Megan L Uhelski, Aysegul Gorur, Ted Shi, German Corrales, Kim N Du, Yan Li, Moran Amit, Claudio E Tatsui, Laurence D Rhines, Patrick M Dougherty, Juan P Cata

Faculty, Staff and Student Publications

Introduction: Currently, cancer pain is viewed as a process orchestrated by the release of pronociceptive molecules and the invasion of neural structures, referred to as perineural invasion (PNI). Cancer pain resulting from PNI is well-documented, but the mechanisms leading to peripheral sensitization because of tumor growth are not fully known.

Methods: A retrospective study was used to examine how the use of anti-inflammatory medications affected preoperative pain in patients with oral squamous cell carcinoma cancer. We then used an in vitro coculture model in which dorsal root ganglion (DRG) neurons were incubated together with Fadu human head and neck squamous …