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Chronic pain is a major health problem affecting more than 1.5 billion people worldwide. Specifically, neuropathic pain and chronic post-surgical pain are debilitating clinical conditions with few efficacious treatments, warranting development of novel therapeutics. Starting with the hypothesis that dysregulated translation regulation pathways may underlie these pain states, we demonstrated that there is a major reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity and increased phosphorylation of mTOR and ERK downstream targets in these persistent pain states. We also hypothesized that activators of AMP-activated protein kinase (AMPK) may represent a novel treatment avenue for the treatment of neuropathic and incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors. The AMP activated protein kinase (AMPK) activators, metformin, resveratrol and A769662, inhibited translation regulation signaling pathways in sensory neurons, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia. We have further demonstrated that local injection of resveratrol, metformin or A769662 and topical application of resveratrol, a potent AMPK activator, into the hindpaw following plantar incision dose-relatedly reverses incision-mediated mechanical hypersensitivity as well as hyperalgesic priming induced by incision. In addition, co-treatment with systemic metformin and local resveratrol at individually sub-efficacious doses at the time of incision blocked acute hypersensitivity and hyperalgesic priming suggesting potential super-additive effects of combined AMPK activator use. These results highlight the importance of signaling to translation control in peripheral sensitization of nociceptors and provide further evidence for activation of AMPK as a novel treatment avenue for acute and chronic pain states.

Cardiac surgery incisional pain can decrease inspiratory effort, alter normal respiratory mechanics, and increase the potential for post-operative pulmonary complications. Post-surgical atelectasis is the most frequent complication after coronary artery bypass grafting (CABG), ranging from 54% to 92%. All types of therapy such as an incentive spirometry (IS), deep breathing exercises (DBE) or continuous positive airway pressure (CPAP) have a valuable role to play in the prevention or the treatment of post-surgical atelectasis. However, the type of therapy that should be used is not completely clear yet. The present research aims to evaluate the benefit of early use of CPAP via mask therapy to treat or prevent post-surgical atelectasis after CABG, particularly in smokers and elderly patients, as compared to regular (IS) therapy. Also, it aims to evaluate the patients' and medical staff's experience about the use of the new method of CPAP via mask therapy. The present research was conducted at King Fahd Armed Forces Hospital in Saudi Arabia between March 2010 and December 2011. It used a mixed methods approach. The first two studies were intervention quantitative studies, which investigated the benefit of CPAP via mask therapy. The others were qualitative studies that evaluated the experience of patients and medical staff regarding CPAP therapy use.A total of 180 patients (male and female) (36 in each group) participated in the two quantitative studies. Ninety two participants (male and female) participated in the qualitative studies. The first quantitative study results showed an improvement in CPAP via mask therapy for half hours every two hours group measurements as compared to IS therapy groups. IC was increased significantly in the "CPAP every two hours group" as compared to control group (IS) (baseline mean for IS group 1.34L and "CPAP every two hours group" 1.42L, post- therapy mean 1.59L and 1.88L respectively, p= 0.037). In addition, when chest physiotherapy was added to the two regimens, the improvement of CPAP therapy measurements became more than IS therapy. Moreover, the patient’s acceptance rate for CPAP therapy every two hours was 93% and the medical staff acceptance rate was 86%. CPAP via mask therapy for half hour every two hours had better outcomes in treating or preventing post-surgical atelectasis after CABG, particularly in smokers and elderly patients. Adding chest physiotherapy led to even better outcomes. The use of the new method of CPAP therapy had high acceptance rate by the participants and medical staff.

Persistent postsurgical pain (PPSP) is reported as recurrent and frequently disabling complication of many surgical procedures. The consequences for PPSP not only reduce the quality of life for patients but also financially tax the health care system, considering the volume of surgical procedures performed annually. Development of chronic pain has been proposed to involve a complex pathophysiology combined with pre-, intra-, and post-operative risk factors. There is no definite recommendation on which factor to assess (in which surgery) and what tools to utilize for conducting a study on PPSP, since many recognized risk factors for PPSP are contradictory. For a comprehensive overview of major PPSP risk factors for identification and possible prevention, we conducted a systematic review and meta-analysis of the published literature on the risk factors across six major surgical groups: breast surgery, chest/thoracic surgery, total hip arthroplasty/total knee arthroplasty (THA/TKA), gynecologic surgery, iliac crest bone harvest (ICBH), and groin hernia repair. Furthermore, to assess the generalizability of the meta-analysis results, we sought to conduct a retrospective, cross-sectional study examining the prevalence and major risk factors of PPSP after cystectomy for bladder cancer. The meta-analysis found that no single risk factor was associated with PPSP across all surgical groups. Age and previous surgery were found to be risk factors for PPSP in gynecologic surgery. For thoracic surgery, male sex and BMI were found as risk factors for PPSP. Surgical duration, presurgical chronic pain, and BMI were risk factors for groin hernia repair. The prevalence of PPSP in our cystectomy study was 22.1%. Female sex and presurgical chronic pain were risk factors significantly associated with PPSP after cystectomy. No risk factors were universally associated with PPSP. Persistent pain after each type of surgical procedure appear to have separate set risk factors among age, BMI, sex, previous surgery, and presurgical pain.

Chronic pain is an ever-present issue and some estimate its cost to society at $635 billion per year. Not only does chronic pain cause increased visits to medical personnel, it also complicates other medical conditions and lowers productivity in the workplace. One area of study includes Chronic Post Surgical Pain (CPSP) in children that have undergone spinal fusion surgery for Adolescent Idiopathic Scoliosis (AIS). Some of the major factors that may lead to CPSP include preoperative pain, psychosocial factors, age, intraoperative nerve injury, acute postoperative pain, and genetics. In order to explore the psychological factors, our lab has employed an Unpredictable Chronic Mild Stress (UCMS) paradigm, which models unforeseen life stressors and depression. Some sensory testing was conducted included Hot Plate and von Frey fiber testing. Previous studies from this lab have shown that adult male mice have hyperalgesia to thermal stimuli following a UCMS paradigm. To further explore this finding, a younger mice cohort of both sexes and a cohort that underwent Maternal Deprivation (MD) were added. Maternal Deprivation is a model of early-childhood stress and older female mice have been shown to have changes in thermal sensitivities as a result of early childhood stressors. Our lab found that stressed young females also exhibit a heightened sensitivity to thermal stimuli at 49°C compared to their male and control counter parts. These results indicate that the thermal sensitivity of young females can be affected by early childhood stress and depression.

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OBJECTIVE: The overall goal of this study was to examine the relationship between preoperative, 1-year post-operative, and 2-year postoperative self-image in adolescents with idiopathic scoliosis undergoing spinal fusion surgery. In addition, a minor goal was to examine the relationship between pre-surgical mental health and post-surgical self-image and satisfaction. Additionally, spinal curvature and preoperative pain were explored in relation to the effect of pre-surgical mental health on post-surgical self-image. Analyses were performed in order to better understand the relationship of corrective surgery to self-image, and self-image's relationship to persistent postoperative pain, which has been recognized as a common clinically significant problem. METHODS: The Scoliosis Research Society Questionnaire-30 and Spinal Appearance Questionnaire were administered to 219 patients enrolled in the Prospective Pediatric Scoliosis study at pre-operative, 1-year post-operative, and 2-year post-operative time points. A subset (n=163) of these patients had complete data. The Scoliosis Research Society Questionnaire-30 includes pain and mental health subscales, which were examined preoperatively for the purpose of this study. Measurements of preoperative curve (Cobb) angle percentage correction were used in the analysis of this data, which were determined using operative notes. The Spinal Appearance Questionnaire (SAQ) includes self-image appearance and expectations subscales, which were examined at the preoperative, 1-year postoperative, and 2-year postoperative time points. RESULTS: There were significant improvements in self-image after surgical intervention in children with idiopathic scoliosis undergoing spinal fusion surgery. Cobb angle percentage correction, preoperative pain scores as determined by the SRS-30, and preoperative mental health scores as determined by the SRS-30 were not significant predictors of postoperative self-image as measured by the SAQ. There is little to no correlation between the preoperative measures and postoperative self-image. CONCLUSIONS: Prior studies have confirmed that pediatric persistent postsurgical pain is a significant health concern, and that presurgical mental health and self-image are factors that contribute to a pediatric patient's longitudinal experience with postsurgical pain. This study shows that there are clinically significant improvements in self-image after surgical intervention in patients with adolescent idiopathic scoliosis undergoing spinal fusion surgery. These findings suggest that preoperative pain, degree of spinal curvature correction, and preoperative mental health are not determinative of postoperative self-image in pediatric populations. Future studies should be conducted on more diverse populations, and take into account measures that may be predictors of poor postoperative self-image, specifically depression and anxiety. In summary it is important to explore the biological mechanisms pertaining to pediatric post-surgical chronic pain and their relation to differences in somatosensory phenotypes in this patient population.

To understand pain processing requires the assessment of an individual’s perception of pain with temporal stimulation over different periods. Offset analgesia (OA), a phenomenon widely studied, refers to a disproportionate decrease in pain experience following a small reduction in temperature during noxious thermal stimulation. OA leads to skin desensitization, causing brief pain inhibition at the stimulation site and leading to adaptation and a decrease in pain scores. To avoid sensitization and habituation during thermal pain procedures, previous studies have utilized protocols in which the thermal stimulation is applied to different areas of the skin (e.g., upper forearm versus lower forearm). The reliability of this thermal pain calibration procedure in producing a nonadaptive effect has been previously tested using pain rating scales. The utilization of neuroimaging to further elucidate these relationships has not been widely studied, but it is likely an important tool to investigate these constructs. Functional near-infrared spectroscopy (fNIRS) is a noninvasive optical imaging technique that measures changes in hemoglobin (Hb) concentrations within the brain using the characteristic absorption spectra of Hb in the near-infrared range. This thesis investigated whether adaptation exists across four conditions of the OA paradigm using fNIRS. Introducing fNIRS to define significant differences in brain metrics (e.g., activated regions of interest) in participants who have undergone surgery and are experiencing chronic pain as well as healthy, pain-free controls could have implications for more accurate measures of OA and more reliable pain treatment options. In this study, noxious thermal stimulation was given to 19 participants on the forearm of the nondominant hand through a commonly used three-temperature OA paradigm with offset, constant, and control trials. Each OA paradigm consisted of four conditions (A, B, C, and D) with a pseudorandom sequence design of three trials. OA was implemented with the participant while real-time fNIRS data were obtained on the subject’s prefrontal and somatosensory cortices, regions known to be involved in pain processing. Hemoglobin responses during the four OA trials were evaluated and compared within experimental conditions. Repeated measures ANOVA was used to analyze the significant differences among conditions. Results showed no significant differences among the four OA trials. The findings of this thesis study indicated that brain response from the prefrontal and somatosensory cortices is not affected within the four OA trials. The consistent brain activation across multiple trials of stimulation suggests an absence of adaptive responses. In line with previous findings, these results imply the reliability of such thermal pain calibration procedures by fNIRS brain imaging. Further investigation with a larger sample size is likely for the verification of the findings from this study. / 2026-02-14T00:00:00Z

Despite recent advances in surgical technique and the development of numerous therapeutic agents, the formation post surgical adhesions (PSA) continues to cause complications for many patients. In this research, we have employed a rational system to develop a novel treatment to address this clinical need. Based on an understanding of the biochemical events that lead to PSA formation, a series of targeted polymeric biomaterials was designed to interrupt the fibrin gel matrix propagation and suppress PSA formation. Using group transfer polymerization, a series of well controlled block copolymers of polyacrylic acid and poly(ethylene glycol-methacrylate) based materials was synthesized. Subsequent functionalization with the pentapeptide Cys-Arg-Glu-Lys-Ala (CREKA) was employed to target the materials to fibrin as a marker of pro-adhesive sites. While preliminary testing of the untargeted materials verified their ability to suppress non-specific protein adsorption to model surfaces, numerous in vitro tests were conducted to study the ability to inhibit fibrin gel propagation. The ability to inhibit both the rate and quantity of fibrinogen deposition to a fibrin coated surface has been demonstrated. In addition, the rate of fibrin gel propagation and the degree of cellular attachment can modulated. Taking advantage of the systematic variation in structure facilitated by the robust synthetic methodology employed, statistical analysis was used to elucidate the structureproperty relationships governing the performance of these materials. The most important factors that lead to enhanced performance in in vitro tests are the length of PEG chain and number of peptide units conjugated to the polymer: increasing PEG chain length and increasing the number of peptides conjugated to the polymer both improve performance in all tests. The synthetic methods that have been developed, in conjunction with the experimental results, will be used to direct future studies, including cytotoxicity and animal studies.

Este estudo objetivou avaliar o perfil clínico e epidemiológico de pacientes submetidos à cirurgia de prótese de quadril e que sofreram complicações relacionadas a esta no pós-operatório. A pesquisa foi realizada no período de 2002 a 2006; a amostra inicial foi composta de 398 cirurgias de pacientes submetidos à Artroplastia Primária de Quadril, realizadas em um hospital escola especializado da Cidade de São Paulo. Em 48 destas cirurgias ocorreram complicações pós-operatórias, compondo a amostra final deste estudo. Houve predominância de indivíduos do sexo feminino (66,7%), com média de idade de 59 anos, casados ou em união estável/amasiado (43,4%), provenientes da cidade de São Paulo (55,3%). Referente à escolaridade a maioria (58,1%) tinha fundamental completo. Quanto à ocupação houve predominância de aposentados e pacientes que desenvolvem atividades técnicas e ocupacionais, ambos com 35,1%. Infecção do quadril foi o motivo predominante para revisão da prótese de quadril (33,3%). A Vancomicina e a Ceftazidima, associadas, foram os antibióticos mais utilizados (58,1%). O estudo contribui para a estruturação de um cuidar multidisciplinar e especializado, pois possibilita o conhecimento da clientela, através de um perfil sociodemográfico e clínico, proporcionando mecanismos para intervenções de modo a transformar a assistência de Enfermagem em Ortopedia e Traumatologia e Reabilitação Física / This study was aimed at evaluating the clinical and epidemiological profile of patients submitted to hip prosthesis surgery who had complications related to it in the post-surgery period. The research was conducted between 2002 and 2006; the initial sample was comprised of 398 surgeries of patients submitted to Primary Hip Arthroplasty, performed at a specialized school hospital in the city of São Paulo. In 48 of those surgeries there were post-surgery complications, thus comprising the final sample of this study. There was a predominance of females (66.7%), with average age of 59, married or with a stable union (43.4%), living in the city of São Paulo (55.3%). Regarding education, most (58.1%) had finished primary school. As for occupation, the majority were retirees and patients that perform technical and occupational activities, both with 35.1%. Hip infection was the most common cause for hip prosthesis revision (33.3%). Vancomycin and ceftazydime, used together, were the most used antibiotics (58.1%). The study helps the development of a multidisciplinary, specialized care because it brings information about the clientele through a socio-demographic and clinical profile, thus providing mechanisms for interventions so as to transform care in Orthopedic and Traumatology Nursing and in Physical Rehabilitation Nursing