Background: Altered autonomic nervous system (ANS) function has been proposed as a mechanism in the development of central sensitisation (CS) and visceral pain hypersensitivity (VPH). The contribution of the parasympathetic nervous system (PNS) and the factors that mediate differences in sensitisation to acid are unclear and their study will clarify risk factors for oesophageal pain hypersensitivity (OPH) in gastrooesophageal reflux disease. Aims: To investigate psychophysiological and pharmacological manipulation of PNS tone in the development of OPH, and to determine factors which predict the development of OPH to acid infusion in healthy volunteers in a validated model of acid induced OPH. Methods: Pain thresholds to electrical stimulation in the proximal oesophagus were determined before and after a 30-minute distal oesophageal infusion of 0.15 mol/L hydrochloric acid in subjects. Sympathetic (SNS) and PNS parameters were measured at baseline and continuously thereafter. Subjects underwent psychological profiling for anxiety, depression, attachment vulnerability and personality type. Using this model, five studies were undertaken: Study 1 a pilot study to trail modulation suitability for further study used. In Study 2, subjects who demonstrated secondary hyperalgesia in the proximal non-acid-exposed oesophagus performed deep or sham breathing. Study 3 subjects, who did not sensitise to acid, underwent a validated stress test to induce OPH. With Study 4, deep breathing with IV saline (placebo) or atropine (PNS antagonist) was used to evaluate deep breathing’s induced PNS tone in OPH reduction. Study 5, a genetic pilot study, exploring the role of the GCH-1 haplotype in VPH. Results: ANS control’s key role in CS was clarified. Deep breathing increased PNS tone and prevented acid-induced OPH in comparison to sham breathing and confirmed increased PNS tone’s reversal of OPH. Psychological factors of anxiety, alexithymia and attachment status influence ANS modulation of CS. Individuals’ predisposition to VPH due to psychogenetic profiles were clarified and their biopsychosocial role illustrated. Conclusions and Inferences: A mechanistic explanation for the analgesic effect of deep breathing is provided with potential therapeutic implications in the treatment of VPH syndromes. Further clinical study is warranted to develop cost-effective treatments for chronic VPH syndromes.

L’interocezione è definita come il senso della condizione fisiologica dell’intero organismo. Le sensazioni interocettive comprendono un ampio raggio di funzioni biologiche sia consce sia inconsce, e costituiscono la dimensione interna del nostro senso del Se. L’obiettivo primario di questa tesi è stato di capire come le percezioni interne del corpo siano in grado di modificare il nostro senso del se e come questi processi possano essere cambiati, modificati e alterati per migliorare il benessere psicofisiologico. Gli scopi di questa dissertazione sono stati 1) capire come gli input interocettivi sono processati e come contribuiscono al nostra percezione del se e al nostro benessere. 2) sviluppare nuove tecnologie per manipolare il sistema interocettivo al fine di promuovere il benessere. 3) testare queste nuove tecnologie interocettive su soggetti sani e su popolazioni cliniche. La tesi propone nuovi contributi sia teorici sia sperimentali. Nella sezione sperimentale, le tecnologie interocettive sono state testate per promuovere il benessere in popolazioni cliniche e non. I risultati hanno indicato che i trattamenti interocettivi possono promuovere il benessere nei soggetti sani e ridurre la severità dei sintomi in soggetti patologici (i.e., con dolore cronico) confermando la possibilità di manipolare la dimensione interocettiva per promuovere il benessere dell’individuo. / Interoception can be defined as the sense of the physiological condition of the entire organism (Craig, 2003). From this point of view interoceptive sensations entail a broad range of relevant biological functions that serve conscious and unconscious processes and constitute the embodied inner dimension of our sense of Self. The main objective of this thesis was to understand how the perceptions that arise from our body are able to shape our sense of Self and moreover, how these processes can be changed, modified, and altered to improve both our physiological both our psychological well-being. The purpose of this dissertation was 1) to understand how interoceptive inputs are processed and how they contribute to our self-perception and well-being. 2) to develop new interoceptive technologies to manipulate the interoceptive system to promote well-being. 3) to test these new technological applications on healthy and clinical populations. The thesis proposes both theoretical both experimental contributes. In the experimental section interoceptive technologies are tested to promote well-being in healthy and clinical populations. Results indicated that “interoceptive treatment” can both promote well-being in healthy subjects both reduce symptoms severity in clinical subjects (i.e. chronic pain) confirming the possibility to manipulate the interoceptive dimension to enhance healthy functioning.

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Background: Work-related stress (WRS) is associated with musculoskeletal pain (MSP), changes in the autonomic nervous system (ANS) and anxiety. Objective: To determine the feasibility of a follow-up study and treatment efficacy of the Reaset Approach on MSP, ANS and State-Trait anxiety. Methods: 15 subjects with WRS and MSP were assigned into 3 groups (Body, Head-Neck, Head-Neck-Body). Each group received a single 25 minute ‘Reaset Approach’ intervention. Heart rate variability (HRV), electro-dermal activity (EDA), State Trait Anxiety (STAI) and MSP were measured. Results: HRV parameters: SDNN increased in 13 of 15 subjects while SD1 and SD2 increased in 12 of 15 subjects. EDA reduced in 10 of 14 subjects. State Anxiety reduced in all subjects and Trait Anxiety reduced in 14 of 15 subjects. MSP reduced in all subjects after the intervention and were still lower three days afterwards. Conclusions: This pilot study determined that a follow-up study can ensue provided minor modifications are implemented and that the ‘Reaset Approach’ has an influence on the ANS, anxiety and MSP. Results do differ between groups. The intervention groups including the head and neck modalities demonstrated better results.:I. Abstract (En) III II. Abstract (De) IV III. Table of Contents V IV. Index of figures VIII V. Index of tables IX VI. Index of abbreviations X 1 Introduction 1 2 Background 2 2.1 Work-related musculoskeletal pain 2 2.2 Work-related stress 3 2.3 Osteopathy and the autonomic nervous system 3 2.4 Stress, pain and osteopathy 4 3 Questions 6 3.1 Feasibility 6 3.2 Treatment effect 6 4 Methods 7 4.1 Study design 7 4.2 Participants 8 4.2.1 Inclusion criteria 8 4.2.2 Exclusion criteria 8 4.2.3 Recruitment 8 4.2.4 Randomization 10 4.3 Parameters 11 4.3.1 Heart rate variability 11 4.3.2 Electro-dermal activity 11 4.3.3 State anxiety 11 4.3.4 Trait anxiety 12 4.3.5 Perceived pain 12 4.4 Measuring Instruments 13 4.4.1 Heart rate variability 13 4.4.2 Electro-dermal Activity 13 4.4.3 State-Trait Anxiety Inventory 13 4.4.4 Short-Form McGill Pain Questionnaire 13 4.5 Interventions 14 4.5.1 Intervention ‘B’: Body 14 4.5.2 Intervention ‘HN’: Head and Neck 16 4.5.3 Intervention ‘HNB’: Head, Neck and Body 16 4.6 Study flow 18 4.7 Statistics 20 5 Results 21 5.1 Autonomic nervous system: Heart rate variability 21 5.1.1 SDNN 22 5.1.2 SD1 25 5.1.3 SD2 28 5.2 Autonomic Nervous System: Electro-dermal activity 31 5.3 Anxiety 34 5.3.1 State anxiety 34 5.3.2 Trait anxiety 37 5.4 Musculoskeletal pain 39 5.4.1 Visual analogue scale 40 5.4.2 Total Short-Form McGill Pain Questionnaire 43 6 Discussion 46 6.1 Discussion of the method 46 6.2 Discussion of the results 50 6.2.1 Autonomic nervous system 50 6.2.1.1 Heart rate variability 50 6.2.1.2 Electro-dermal activity 51 6.2.2 Anxiety 51 6.2.2.1 State anxiety 51 6.2.2.2 Trait Anxiety 52 6.2.3 Musculoskeletal pain 52 6.3 Suggestions for future research 53 7 Conclusion 54 8 Literature 55 9 Addendum 63 9.1 Table: SF-MPQ with Sensory, Affective and Evaluative dimension 63 9.2 Patient Information Sheet 64 9.3 Structured telephone interview 70 9.4 Structured pre-treatment interview 72 9.5 SF-MPQ permission 73 9.6 SF-MPQ 74 9.7 STAI License 76 9.8 STAI forms Y-1 and Y-2 77 / Hintergrund: Arbeitsbedingter Stress (ABS) ist verbunden mit muskelschmerzen, Veränderungen im autonomen Nervensystem (ANS) und Angst. Ziel: Machbarkeit einer Follow-up-Studie und Wirksamkeit der Behandlung des Reaset Ansatzes auf ANS, Muskelschmerzen und State und Trait- Angst bestimmen. Methoden: 15 Patienten mit ABS und Muskelschmerzen wurden in 3 Gruppen eingeteilt (Körper, Kopf-Hals, Kopf-Hals-Körper). Jede Gruppe erhielt eine einzige 25 Minuten dauernde 'Reaset Approach’-Behandlung. Herzfrequenzvariabilität (HRV), elektro-dermale Aktivität (EDA), State-Trait-Angstsinventar (STAI) und Muskelschmerzen (SF-MPQ) wurden gemessen. Ergebnisse: Die HRV-wert: SDNN ist bei 13 von 15 Probanden erhöht, während SD1 und SD2 bei 12 von 15 Probanden zugenommen hat. EDA war bei 10 von 14 Probanden reduziert. Die State-Angst hat bei allen Probanden und die Trait-Angst bei 14 der 15 Probanden abgenommen. Muskelschmerzen waren bei alle Probanden anschließend an und drei Tage nach der Intervention reduziert. Schlussfolgerung: Diese Pilotstudie hat gezeigt, dass eine Follow-up-Studie fortgesetzt werden kann, sofern kleinere Änderungen durchgeführt werden. Die 'Reaset Approach’ hat einen günstigen Einfluss auf die ANS, State-Trait-Angst und Muskelschmerzen. Ergebnisse zwischen den Gruppen sind unterschiedlich. Die Interventionsgruppen mit einschließlich der Kopf-Hals-Modalitäten zeigten bessere Ergebnisse..:I. Abstract (En) III II. Abstract (De) IV III. Table of Contents V IV. Index of figures VIII V. Index of tables IX VI. Index of abbreviations X 1 Introduction 1 2 Background 2 2.1 Work-related musculoskeletal pain 2 2.2 Work-related stress 3 2.3 Osteopathy and the autonomic nervous system 3 2.4 Stress, pain and osteopathy 4 3 Questions 6 3.1 Feasibility 6 3.2 Treatment effect 6 4 Methods 7 4.1 Study design 7 4.2 Participants 8 4.2.1 Inclusion criteria 8 4.2.2 Exclusion criteria 8 4.2.3 Recruitment 8 4.2.4 Randomization 10 4.3 Parameters 11 4.3.1 Heart rate variability 11 4.3.2 Electro-dermal activity 11 4.3.3 State anxiety 11 4.3.4 Trait anxiety 12 4.3.5 Perceived pain 12 4.4 Measuring Instruments 13 4.4.1 Heart rate variability 13 4.4.2 Electro-dermal Activity 13 4.4.3 State-Trait Anxiety Inventory 13 4.4.4 Short-Form McGill Pain Questionnaire 13 4.5 Interventions 14 4.5.1 Intervention ‘B’: Body 14 4.5.2 Intervention ‘HN’: Head and Neck 16 4.5.3 Intervention ‘HNB’: Head, Neck and Body 16 4.6 Study flow 18 4.7 Statistics 20 5 Results 21 5.1 Autonomic nervous system: Heart rate variability 21 5.1.1 SDNN 22 5.1.2 SD1 25 5.1.3 SD2 28 5.2 Autonomic Nervous System: Electro-dermal activity 31 5.3 Anxiety 34 5.3.1 State anxiety 34 5.3.2 Trait anxiety 37 5.4 Musculoskeletal pain 39 5.4.1 Visual analogue scale 40 5.4.2 Total Short-Form McGill Pain Questionnaire 43 6 Discussion 46 6.1 Discussion of the method 46 6.2 Discussion of the results 50 6.2.1 Autonomic nervous system 50 6.2.1.1 Heart rate variability 50 6.2.1.2 Electro-dermal activity 51 6.2.2 Anxiety 51 6.2.2.1 State anxiety 51 6.2.2.2 Trait Anxiety 52 6.2.3 Musculoskeletal pain 52 6.3 Suggestions for future research 53 7 Conclusion 54 8 Literature 55 9 Addendum 63 9.1 Table: SF-MPQ with Sensory, Affective and Evaluative dimension 63 9.2 Patient Information Sheet 64 9.3 Structured telephone interview 70 9.4 Structured pre-treatment interview 72 9.5 SF-MPQ permission 73 9.6 SF-MPQ 74 9.7 STAI License 76 9.8 STAI forms Y-1 and Y-2 77