Synopsis of an engineering solution for a painful problem Phantom Limb Pain

This paper is synopsis of a recently proposed solution for treating patients who suffer from Phantom Limb Pain (PLP). The underpinning approach of this research and development project is based on an extension of “mirror box” therapy which has had some promising results in pain reduction. An outline of an immersive individually tailored environment giving the patient a virtually realised limb presence, as a means to pain reduction is provided. The virtual 3D holographic environment is meant to produce immersive, engaging and creative environments and tasks to encourage and maintain patients’ interest, an important aspect in two of the more challenging populations under consideration (over-60s and war veterans). The system is hoped to reduce PLP by more than 3 points on an 11 point Visual Analog Scale (VAS), when a score less than 3 could be attributed to distraction alone

Synopsis of an engineering solution for a painful problem: Phantom limb pain

This paper is synopsis of a recently proposed solution for treating patients who suffer from Phantom Limb Pain (PLP). The underpinning approach of this research and development project is based on an extension of "mirror box" therapy which has had some promising results in pain reduction. An outline of an immersive individually tailored environment giving the patient a virtually realised limb presence, as a means to pain reduction is provided. The virtual 3D holographic environment is meant to produce immersive, engaging and creative environments and tasks to encourage and maintain patients' interest, an important aspect in two of the more challenging populations under consideration (over-60s and war veterans). The system is hoped to reduce PLP by more than 3 points on an 11 point Visual Analog Scale (VAS), when a score less than 3 could be attributed to distraction alone. Copyright © 2014 SCITEPRESS - Science and Technology Publications. All rights reserved.Published versio

The Effects of Insoles on Biomechanics of Standing Balance and Walking of Trans-Femoral Amputees

As the world’s population ages, it is expected that the number of people having experienced amputations will grow, alongside comorbidities. Lifestyle adaptations associated with lower limb amputation are likely to occur and, with this, there is likely an impact on mobility and balance. This research has initially investigated, via a comprehensive survey, the impact of lower limb amputation and prosthetic use on the lives of amputees with a focus on their balance and mobility during daily activities. The survey consisted of parts of the Prosthesis Evaluation Questionnaire (PEQ), the Activities-Specific Balance Confidence (ABC) Scale, and the Oswestry Disability Index (ODI). The results of the survey (155 participants in all levels of lower limb amputation) showed that the majority of LLAs suffered from stump and intact-side pain, frequent falling, LBP with impact on their functionality, and a lower level of balance confidence. A considerable proportion of respondents were at risk of falling and needed intervention to improve their balance. According to the mentioned problems which LLAs deal with on a daily basis and the effectiveness of insoles use on similar balance problems and lower limb pains among non-amputees, it was supposed the insoles used on the intact side of LLAs would improve their situation. Therefore, biomechanical research was conducted to examine the effect of insoles use on perturbed standing balance and self-selected speed walking of TF amputees (11 participants) and a group of non-amputees (14 participants). Data was collected via 3D motion analysis systems, including high-speed cameras and force platforms. The function level of amputee participants was evaluated according to spatio-temporal variables of their walking and their responses to the ABC scale and PEQ-Mobility parts of the survey. Lower self-selected speed and asymmetrical walking compared to non-amputees indicated that amputee participants had lower levels of function. Results of the ABC scale questionnaire showed that most of them had moderate functional level (three amputees with good and one with a low level of functionality). These results corresponded with their PEQ-M scores. The kinematic and kinetic results of walking showed asymmetrical performance of amputees’ limbs with a prominent role of the intact limb. However, the relationship between the centre of mass (COM) and centre of pressure (COP) with lateral borders of BOS as the balance did not exhibit any difference between amputees and non-amputees, which shows proper balance maintenance of amputees during walking. For studying the biomechanics of standing balance, a perturbation was applied by a front/back-pulling load (2.5% of body weight) to the waist of each participant which, upon release, respectively induced backwards and forward falling. The observed changes in COP, COM, ground reaction forces and joint moments during standing and in response to the perturbation indicated that the intact limb of TF amputees had the main role in their balance, which resulted in an asymmetrical posture. Both groups used ankle movements to maintain balance in reaction to the perturbation. Insoles use was associated with changes in a very limited number of biomechanical variables for non-amputees and in none of the amputees’ biomechanical variables. But, the quantitative evaluation of insoles showed most participants were satisfied with insoles and felt more comfortable in their daily activity during their use. The results of this research (including both survey and biomechanical studies) affirm the necessity of providing more support (in the form of medical and musculoskeletal rehabilitation interventions) for LLAs to address the current issues, particularly with balance and their function in daily activities. The use of insoles in the initial phase of gait training after the first prosthesis fit might be beneficial for LLAs

Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists

New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes

Medical robots for MRI guided diagnosis and therapy

Magnetic Resonance Imaging (MRI) provides the capability of imaging tissue with fine resolution and superior soft tissue contrast, when compared with conventional ultrasound and CT imaging, which makes it an important tool for clinicians to perform more accurate diagnosis and image guided therapy. Medical robotic devices combining the high resolution anatomical images with real-time navigation, are ideal for precise and repeatable interventions. Despite these advantages, the MR environment imposes constraints on mechatronic devices operating within it. This thesis presents a study on the design and development of robotic systems for particular MR interventions, in which the issue of testing the MR compatibility of mechatronic components, actuation control, kinematics and workspace analysis, and mechanical and electrical design of the robot have been investigated. Two types of robotic systems have therefore been developed and evaluated along the above aspects. (i) A device for MR guided transrectal prostate biopsy: The system was designed from components which are proven to be MR compatible, actuated by pneumatic motors and ultrasonic motors, and tracked by optical position sensors and ducial markers. Clinical trials have been performed with the device on three patients, and the results reported have demonstrated its capability to perform needle positioning under MR guidance, with a procedure time of around 40mins and with no compromised image quality, which achieved our system speci cations. (ii) Limb positioning devices to facilitate the magic angle effect for diagnosis of tendinous injuries: Two systems were designed particularly for lower and upper limb positioning, which are actuated and tracked by the similar methods as the first device. A group of volunteers were recruited to conduct tests to verify the functionality of the systems. The results demonstrate the clear enhancement of the image quality with an increase in signal intensity up to 24 times in the tendon tissue caused by the magic angle effect, showing the feasibility of the proposed devices to be applied in clinical diagnosis

Imaging Pain And Brain Plasticity: A Longitudinal Structural Imaging Study

Chronic musculoskeletal pain is a leading cause of disability worldwide yet the mechanisms of chronification and neural responses to effective treatment remain elusive. Non-invasive imaging techniques are useful for investigating brain alterations associated with health and disease. Thus the overall goal of this dissertation was to investigate the white (WM) and grey matter (GM) structural differences in patients with musculoskeletal pain before and after psychotherapeutic intervention: cognitive behavioral therapy (CBT). To aid in the interpretation of clinical findings, we used a novel porcine model of low back pain-like pathophysiology and developed a post-mortem, in situ, neuroimaging approach to facilitate translational investigation. The first objective of this dissertation (Chapter 2) was to identify structural brain alterations in chronic pain patients compared to healthy controls. To achieve this, we examined GM volume and diffusivity as well as WM metrics of complexity, density, and connectivity. Consistent with the literature, we observed robust differences in GM volume across a number of brain regions in chronic pain patients, however, findings of increased GM volume in several regions are in contrast to previous reports. We also identified WM changes, with pain patients exhibiting reduced WM density in tracts that project to descending pain modulatory regions as well as increased connectivity to default mode network structures, and bidirectional alterations in complexity. These findings may reflect network level dysfunction in patients with chronic pain. The second aim (Chapter 3) was to investigate reversibility or neuroplasticity of structural alterations in the chronic pain brain following CBT compared to an active control group. Longitudinal evaluation was carried out at baseline, following 11-week intervention, and a four-month follow-up. Similarly, we conducted structural brain assessments including GM morphometry and WM complexity and connectivity. We did not observe GM volumetric or WM connectivity changes, but we did discover differences in WM complexity after therapy and at follow-up visits. To facilitate mechanistic investigation of pain related brain changes, we used a novel porcine model of low back pain-like pathophysiology (Chapter 6). This model replicates hallmarks of chronic pain, such as soft tissue injury and movement alteration. We also developed a novel protocol to perform translational post-mortem, in situ, neuroimaging in our porcine model to reproduce WM and GM findings observed in humans, followed by a unique perfusion and immersion fixation protocol to enable histological assessment (Chapter 4). In conclusion, our clinical data suggest robust structural brain alterations in patients with chronic pain as compared to healthy individuals and in response to therapeutic intervention. However, the mechanism of these brain changes remains unknown. Therefore, we propose to use a porcine model of musculoskeletal pain with a novel neuroimaging protocol to promote mechanistic investigation and expand our interpretation of clinical findings

The effects of distraction, relaxation, and guided imagery on procedural fear and pain in children

The fear and pain of medical procedures are a source of great distress to children. Techniques such as distraction, relaxation and guided imagery help children to cope, and in some cases, have a marked influence on the experience of fear and pain during painful medical procedures. However, the effects, embedded in the relationships between consciousness, imagery, fear and pain, are unclear, particularly with regard to the clinical (as opposed to the laboratory) reality of procedural pain. The aim of this thesis was to empirically account for the therapeutic effects of distraction, relaxation, and imagery on procedural fear and pain in children and to offer a model based on a constructive view of experience allied to recent advances in neurophysiology that could account for the effects. Two studies were undertaken to address this aim. The first study investigated the effects of cartoon distraction on fear and pain in children undergoing venepuncture. The second study investigated the independent and combined effects of relaxation and imagery on fear and pain in children also undergoing venepuncture. The studies indicated that relaxation, distraction and imagery reduced procedural fear. Procedural pain was not affected by relaxation but distraction showed positive effects as did imagery, particularly if procedural pain was defined in terms of its sensory and emotional components. These effects are explained using a model based on a top-down constructivist view of the psychology and neurophysiology of fear, pain, imagery and consciousness. The neurophysiological components of the model comprised the amygdala, anterior cingulate cortex and association areas within a working memory view of consciousness. The constructivist perspective held that during relaxation the child’s cognitive, emotional and sensorial quality were largely based on the ‘reality’ of the procedure room, but that during imagery and perhaps distraction, the qualia were located elsewhere. The thesis concludes with the relevance of the model for clinical practice and implications for further psychological and neurophysiological research.Doctor of Philosoph

Infrared Thermography for the Assessment of Lumbar Sympathetic Blocks in Patients with Complex Regional Pain Syndrome

[ES] El síndrome de dolor regional complejo (SDRC) es un trastorno de dolor crónico debilitante que suele afectar a una extremidad, y se caracteriza por su compleja e incomprendida fisiopatología subyacente, lo que supone un reto para su diagnóstico y tratamiento. Para evitar el deterioro de la calidad de vida de los pacientes, la consecución de un diagnóstico y tratamiento tempranos marca un punto de inflexión. Entre los diferentes tratamientos, los bloqueos simpáticos lumbares (BSLs) tienen como objetivo aliviar el dolor y reducir algunos signos simpáticos de la afección. Este procedimiento intervencionista se lleva a cabo inyectando anestesia local alrededor de los ganglios simpáticos y, hasta ahora, se realiza frecuentemente bajo el control de diferentes técnicas de imagen, como los ultrasonidos o la fluoroscopia. Dado que la termografía infrarroja (TIR) ha demostrado ser una herramienta eficaz para evaluar la temperatura de la piel, y teniendo en cuenta el efecto vasodilatador que presentan los anestésicos locales inyectados, se ha considerado el uso de la IRT para la evaluación de los BSLs. El objetivo de esta tesis es, estudiar la capacidad de la TIR como una técnica complementaria para la evaluación de la eficacia en la ejecución de los BSLs. Para cumplir este objetivo, se han realizado tres estudios implementando la TIR en pacientes diagnosticados de SDRC de miembros inferiores sometidos a BSLs. El primer estudio se centra en la viabilidad de la TIR como herramienta complementaria para la evaluación de la eficacia ejecución de los BSLs. Cuando se realizan los BSLs, la colocación correcta de la aguja es crítica para llevar realizar el procedimiento técnicamente correcto y, en consecuencia, para lograr los resultados clínicos deseados. Para verificar la posición de la aguja, tradicionalmente se han utilizado técnicas de imagen, sin embargo, los BSLs bajo control fluoroscópico no siempre aseguran su exacta ejecución. Por este motivo, se han aprovechado las alteraciones térmicas inducidas por los anestésicos locales y se han evaluado mediante la TIR. Así, cuando en las imágenes infrarrojas se observaron cambios térmicos en la planta del pie afectado tras la inyección de lidocaína, se consideró que el BSL era exitoso. El segundo estudio trata del análisis cuantitativo de los datos térmicos recogidos en el entorno clínico a partir de diferentes parámetros basados en las temperaturas extraídas de ambos pies. Según los resultados, para predecir adecuadamente los BSLs exitosos, se deberían analizar las temperaturas de las plantas de los pies durante los primeros cuatro minutos tras la inyección del anestésico local. Así, la aplicación de la TIR en el entorno clínico podría ser de gran ayuda para evaluar la eficacia de ejecución de los BSLs mediante la evaluación de las temperaturas de los pies en tiempo real. Por último, el tercer estudio aborda el análisis cuantitativo mediante la implementación de herramientas de machine learning (ML) para evaluar su capacidad de clasificar automáticamente los BSLs. En este estudio se han utilizado una serie de características térmicas extraídas de las imágenes infrarrojas para evaluar cuatro algoritmos de ML para tres momentos diferentes después del instante de referencia (inyección de lidocaína). Los resultados indican que los cuatro modelos evaluados presentan buenos rendimientos para clasificar automáticamente los BSLs entre exitosos y fallidos. Por lo tanto, la combinación de parámetros térmicos junto con de clasificación ML muestra ser eficaz para la clasificación automática de los procedimientos de BSLs. En conclusión, el uso de la TIR como técnica complementaria en la práctica clínica diaria para la evaluación de los BSLs ha demostrado ser totalmente eficaz. Dado que es un método objetivo y relativamente sencillo de implementar, puede permitir que los médicos especialistas en dolor identifiquen los bloqueos realizados fallidos y, en consecuencia, puedan revertir esta situación.[CA] La síndrome de dolor regional complex (SDRC) és un trastorn de dolor crònic debilitant que sol afectar una extremitat, i es caracteritza per la seua complexa i incompresa fisiopatologia subjacent, la qual cosa suposa un repte per al seu diagnòstic i tractament. Per a evitar la deterioració de la qualitat de vida dels pacients, la consecució d'un diagnòstic i tractament primerencs marca un punt d'inflexió. Entre els diferents tractaments , els bloquejos simpàtics lumbars (BSLs) tenen com a objectiu alleujar el dolor i reduir alguns signes simpàtics de l'afecció. Aquest procediment intervencionista es duu a terme injectant anestèsia local al voltant dels ganglis simpàtics i, fins ara, es realitza freqüentment sota el control de diferents tècniques d'imatge, com els ultrasons o la fluoroscopia. Atés que la termografia infraroja (TIR) ha demostrat ser una eina eficaç per a avaluar la temperatura de la pell, i tenint en compte l'efecte vasodilatador que presenten els anestèsics locals injectats, s'ha considerat l'ús de la TIR per a l'avaluació dels BSLs. L'objectiu d'aquesta tesi és, estudiar la capacitat de la TIR com una tècnica complementària per a l'avaluació de l'eficàcia en l'execució dels BSLs. Per a complir aquest objectiu, s'han realitzat tres estudis implementant la TIR en pacients diagnosticats de SDRC de membres inferiors sotmesos a BSLs. El primer estudi avalua la viabilitat de la TIR com a eina complementària per a l'analisi de l'eficàcia en l'execució dels BSLs. Quan es realitzen els BSLs, la col·locació correcta de l'agulla és crítica per a dur a terme el procediment tècnicament correcte i, en conseqüència, per a aconseguir els resultats clínics desitjats. Per a verificar la posició de l'agulla, tradicionalment s'han utilitzat tècniques d'imatge, no obstant això, els BSLs baix control fluoroscòpic no sempre asseguren la seua exacta execució. Per aquest motiu, s'han aprofitat les alteracions tèrmiques induïdes pels anestèsics locals i s'han avaluat mitjançant la TIR. Així, quan en les imatges infraroges es van observar canvis tèrmics en la planta del peu afectat després de la injecció de lidocaIna, es va considerar que el BSL era exitós. El segon estudi tracta de l'anàlisi quantitativa de les dades tèrmiques recollides en l'entorn clínic a partir de diferents paràmetres basats en les temperatures extretes d'ambdós peus. Segons els resultats, per a predir adequadament l'execució exitosa d'un BSL, s'haurien d'analitzar les temperatures de les plantes dels peus durant els primers quatre minuts després de la injecció de l'anestèsic local. Així, l'implementació de la TIR en l'entorn clínic podria ser de gran ajuda per a avaluar l'eficàcia d'execució dels BSLs mitjançant l'avaluació de les temperatures dels peus en temps real. El tercer estudi aborda l'anàlisi quantitativa mitjançant la implementació d'eines machine learning (ML) per a avaluar la seua capacitat de classificar automàticament els BSLs. En aquest estudi s'han utilitzat una sèrie de característiques tèrmiques extretes de les imatges infraroges per a avaluar quatre algorismes de ML per a tres moments diferents després de l'instant de referència (injecció de lidocaïna). Els resultats indiquen que els quatre models avaluats presenten bons rendiments per a classificar automàticament els BSLs en exitosos i fallits. Per tant, la combinació de paràmetres tèrmics juntament amb models de classificació ML mostra ser eficaç per a la classificació automàtica dels procediments de BSLs. En conclusió, l'ús de la TIR com a tècnica complementària en la pràctica clínica diària per a l'avaluació dels BSLs ha demostrat ser totalment eficaç. Atés que és un mètode objectiu i relativament senzill d'implementar, pot ajudar els metges especialistes en dolor a identificar els bloquejos realitzats fallits i, en conseqüència, puguen revertir aquesta situació.[EN] Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that usually affects one limb, and it is characterized by its misunderstood underlying pathophysiology, resulting in both challenging diagnosis and treatment. To avoid the patients' impairment quality of life, the achievement of both an early diagnosis and treatment marks a turning point. Among the different treatment approaches, lumbar sympathetic blocks (LSBs) are addressed to alleviate the pain and reduce some sympathetic signs of the condition. This interventional procedure is performed by injecting local anaesthetic around the sympathetic ganglia and, until now, it has been performed under different imaging techniques, including the ultrasound or the fluoroscopy approaches. Since infrared thermography (IRT) has proven to be a powerful tool to evaluate skin temperatures and taking into account the vasodilatory effects of the local anaesthetics injected in the LSB, the use of IRT has been considered for the LSBs assessment. Therefore, the purpose of this thesis is to evaluate the capability of IRT as a complementary assessment technique for the LSBs procedures performance. To fulfil this aim, three studies have been conducted implementing the IRT in patients diagnosed with lower limbs CRPS undergoing LSBs. The first study focuses on the feasibility of IRT as a complementary assessment tool for LSBs performance, that is, for the confirmation of the proper needle position. When LSBs are performed, the correct needle placement is critical to carry out the procedure technically correct and, consequently, to achieve the desired clinical outcomes. To verify the needle placement position, imaging techniques have traditionally been used, however, LSBs under radioscopic guidance do not always ensure an exact performance. For this reason, the thermal alterations induced by the local anaesthetics, have been exploited and assessed by means of IRT. Thus, the LSB procedure was considered successfully performed when thermal changes within the affected plantar foot were observed in the infrared images after the lidocaine injection. The second study deals with the quantitative analysis of the thermal data collected in the clinical setting through the evaluation of different temperature-based parameters extracted from both feet. According to the results, the proper LSB success prediction could be achieved in the first four minutes after the block through the evaluation of the feet skin temperatures. Therefore, the implementation of IRT in the clinical setting might be of great help in assessing the LSBs performance by evaluating the plantar feet temperatures in real time. Finally, the third study addresses the quantitative analysis by implementing machine learning (ML) tools to assess their capability to automatically classify LSBs. In this study, a set of thermal features retrieved from the infrared images have been used to evaluate four ML algorithms for three different moments after the baseline time (lidocaine injection). The results indicate that all four models evaluated present good performance metrics to automatically classify LSBs into successful and failed. Therefore, combining infrared features with ML classification models shows to be effective for the LSBs procedures automatic classification. In conclusion, the use of IRT as a complementary technique in daily clinical practice for LSBs assessment has been evidenced entirely effective. Since IRT is an objective method and it is not very demanding to perform, it is of great help for pain physicians to identify failed procedures, and consequently, it allow them to reverse this situation.Cañada Soriano, M. (2022). Infrared Thermography for the Assessment of Lumbar Sympathetic Blocks in Patients with Complex Regional Pain Syndrome [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/181699TESI

The Prediction of Nociceptive Neural Activity in Passive Tissues following Lumbar Spine Flexion

Low back pain is a costly and debilitating disorder; however, most cases are categorized as being non-specific: low back pain without an identifiable origin or cause. Non-specific low back pain can be broadly considered and treated as either musculoskeletal disorders or pain disorders. In the musculoskeletal case, mechanics and loading history are believed to disrupt or damage tissues in the low back, which then generate nociceptive signals to be interpreted as pain. If the low back pain is a pain disorder, the disruption or damage is not with the tissues of the lower back, but rather the nervous system that transmits or interprets these nociceptive signals. Additionally, these subcategories of non-specific low back pain are not wholly independent since mechanical exposures can influence nervous system activity and vice versa. A specific outcome of this interconnectedness between mechanics and neural encoding is that a mechanical exposure can alter our ability to detect mechanical loads or mechanical sensitivity. One mechanical exposure that is linked to low back pain development and has been documented to alter neural activity is lumbar spine flexion. The purpose of this thesis was to determine the extent and mechanisms underlying how lumbar spine flexion can alter lower back mechanical sensitivity through a combination of viscoelastic creep and muscle activity, and to determine the implications those changes could have on the development of low back pain. The methods undertaken to achieve this thesis’ purpose were a combination of in-vivo human laboratory experiments, ex-vivo benchtop histology and mechanical testing, and in-silico modelling across four studies. Studies 1 and 2 quantified how mechanical sensitivity was altered over time in response to static and repetitive lumbar spine flexion respectively, Study 3 quantified the innervation properties of lumbar spine tissues, and Study 4 simulated mechanical exposures before and after lumbar spine flexion exposures to determine the nociceptive neural activity those exposures and conditions could generate. The first two studies employed a similar design and methodology measuring mechanical sensitivity and biomechanical variables before and up to 40 minutes after a 10-minute lumbar spine flexion exposure. For Study 1, the exposure was a static, seated, maximal lumbar spine flexion exposure and for Study 2, the exposure was a repetitive, standing, maximal lumbar spine flexion exposure. A custom motorized pressure algometer was constructed for these studies and used to track three measures of mechanical sensitivity—pressure-pain threshold, stimulus intensity, and stimulus unpleasantness—in the lower back and tibial shaft. Accelerometry was used in both studies to track the development and recovery from viscoelastic creep through lumbar spine flexion range of motion, and surface electromyography was used to determine flexion-relaxation (mean amplitude) in Study 1, and muscle fatigue (mean power frequency) in Study 2. Isometric joint strength and ratings of perceived exertion were also measured in Study 2. These data were fed into two main statistical processes: the first aimed to determine the time-course of mechanical sensitivity changes in the lower back relative to the tibial control site, and the second was to determine if any of the biomechanical variables (creep, muscle use, strength) or tibial mechanical sensitivities could predict lower back mechanical sensitivity changes. The static exposure generated a 10.3% creep response (4.4 ± 2.7°) in flexion range of motion that lasted for at least 40 minutes after the exposure. This exposure caused a transient increase in lower back stimulus unpleasantness but otherwise did not affect mechanical sensitivity nor did it affect flexion-relaxation. The strongest predictor of lower back mechanical sensitivity throughout the static exposure was the tibial surrogate; however, the magnitude of creep was also a significant predictor of changes in lower back pressure-pain thresholds. Despite being significant, these significant predictors could not explain the majority to the variance in mechanical sensitivity, and these changes appear more related to emotional affect than a physiological response. Study 1 concluded that a static lumbar spine flexion exposure that did not incorporate muscle activity did not alter nociceptive activity but could shape how nociceptive activity is experienced. The repetitive exposure generated a 5.0% creep response (2.7 ± 1.4°) in flexion range of motion dissipated within 5 minutes of the exposure ending. This exposure caused an immediate and transient decrease in lumbar spine extensor mean power frequency (5.1%) and lower back joint strength (9.8%) indicative of muscle fatigue, and a delayed 13.6% increase in lower back pressure-pain thresholds occurring 10 minutes after the exposure ended. Like Study 1, tibial mechanical sensitivities were the strongest predictor of lower back mechanical sensitivities, however interaction terms between these tibial surrogates and either creep magnitude or fatigue indicators (mean power frequency and strength) were also significant predictors. The delayed desensitization following this repetitive exposure was believed to arise from a combination of creep development and muscle use. The third study used lumbar spine tissues harvested from four cadaveric donors to determine the relative concentration of four neural membrane molecules (Protein Gene Product 9.5 (PGP9.5), Calcitonin Gene-Related Peptide, Bradykinin B1-Receptor, and Acid-Sensing Ion Channel 3 (ASIC3)) relevant to detecting mechanical stimuli in three tissues (dermal skin, superficial posterior annulus fibrosus, and the supraspinous-interspinous ligament complex) using Western Blotting. Only PGP9.5 and ASIC3 were found consistently in any of the three tissues. PGP9.5 had similar concentrations in skin and ligament, both of which were at least 12.8 times higher than in annular tissues. ASIC3 was most common in skin, followed by ligament, then annulus fibrosus, however the ratio of ASIC3:PGP9.5 was highest in annular tissue. The fourth study documents a model of nociceptive activity that predicts the likelihood that three exposures (pressure-pain threshold, flexion range of motion, and tissue failure) would generate nociceptive activity in the brainstem given a tissue (skin, annulus, or ligament), a viscoelastic state, ζ(t), and a muscle activity state, ϕ(t). The model simulated a single tissue-exposure combination for a sample of 100 mechanical sensitivities derived from the data in Studies 1 and 2. The model itself consisted of a Sensitivity Module that converted a tissue stress to an electrical current and a Neurological Module that used the electrical current to simulate the behaviour of a network of Hodgkin-Huxley neurons. The pressure-pain threshold exposure was used to validate the model and derive values for ζ(t) and ϕ(t), which were then applied to the other two exposures in annular and ligament tissues. While ζ(t), representing any effects related to creep following lumbar spine flexion, had minimal effects on nociceptive neural activity, ϕ(t), representing muscle activity-related effects of lumbar spine flexion, could inhibit nociceptive activity substantially. A major prediction from the model is that annulus fibrosus failure would be unlikely to generate any nociceptive activity in 12% of the population, and that characteristics of the exposure could increase that percentage to as many as 99.9% depending on the mode of failure. Flexion range of motion consistently generated no nociceptive activity in all tissues and conditions, and ligament failure consistently generated nociceptive activity regardless of other factors. While both viscoelastic creep and muscle activity related to lumbar spine flexion can influence mechanical sensitivity, the effects of muscle activity were more prominent, and could meaningfully influence the connection between tissue disruption and low back pain. These effects were most notable in exposures that have the potential to damage the annulus fibrosus