The aetiology of sensory changes seen in women with pelvic floor dysfunction A thesis submitted to the University of Manchester for the degree of Doctor of Philosophy in the Faculty of Biology, Medicine and Health 2019 Dr Charlotte Mahoney School of Medical Sciences and Division of Developmental Biology and Medicine 1 Contents List of figures ........................................................................................................ 7 List of tables ....................................................................................................... 10 List of abbreviations ............................................................................................ 15 1 Introduction .................................................................................................. 19 1.1 The Pelvic Floor ...................................................................................... 19 1.1.1 Anatomy of the Pelvic Floor ................................................................... 19 1.1.2 Neuroanatomy of the Pelvic Floor ........................................................... 22 1.1.3 Pelvic floor dysfunction ......................................................................... 30 1.1.4 The aetiology of pelvic floor dysfunction.................................................. 31 1.2 Physiology of sensation ............................................................................ 39 1.2.1 Sensory pathways ................................................................................ 39 1.2.2 Nerve fibres ........................................................................................ 39 1.2.3 Sensory receptors ................................................................................ 41 1.3 Nerve regeneration ................................................................................. 41 1.3.1 The physiology of nerve regeneration ..................................................... 41 1.3.2 Time frame for nerve regeneration ......................................................... 42 1.4 Treatment of nerve injury ........................................................................ 42 1.5 Neurophysiology: sensation testing ........................................................... 43 1.5.1 Nerve conduction studies ...................................................................... 43 1.5.2 Somatosensory evoked potentials .......................................................... 44 1.5.3 Quantitative sensory testing .................................................................. 44 1.5.4 Current Perception Thresholds ............................................................... 47 1.5.5 Comparison of CPT and QST .................................................................. 47 1.6 Pelvic floor dysfunction and sensation ........................................................ 50 1.6.1 Pelvic organ prolapse ........................................................................... 50 1.6.2 Stress incontinence .............................................................................. 52 1.6.3 Urge incontinence ................................................................................ 52 1.6.4 Painful bladder syndrome ...................................................................... 53 1.6.5 Faecal incontinence .............................................................................. 57 2 1.6.6 Female sexual dysfunction .................................................................... 57 1.7 Measuring sensation of vaginal tone .......................................................... 61 1.8 Computer interviewing............................................................................. 61 1.9 Identifying the research question .............................................................. 64 1.9.1 Hypothesis .......................................................................................... 64 1.9.2 Aims .................................................................................................. 65 1.9.3 Objectives ........................................................................................... 65 2 Materials and methods ................................................................................... 67 2.1 Quantitative sensory testing ..................................................................... 67 2.1.1 Sensory testing equipment .................................................................... 67 2.1.2 Vibration sensation .............................................................................. 70 2.1.3 Temperature sensation ......................................................................... 70 2.2 Pelvic organ prolapse .............................................................................. 71 3 Female genital stretch sensation ...................................................................... 72 3.1 Introduction ........................................................................................... 72 3.2 Materials and Methods ............................................................................. 73 3.2.1 Study design ....................................................................................... 73 3.2.2 Recruitment ........................................................................................ 73 3.2.3 Study entry ......................................................................................... 75 3.2.4 Demographic Data ............................................................................... 75 3.2.5 Stretch testing equipment ex vivo experiments........................................ 75 3.2.6 Psychophysical methodology ................................................................. 76 3.2.7 Repeatability ....................................................................................... 80 3.2.8 Statistical Analysis ............................................................................... 81 3.3 Results .................................................................................................. 83 3.3.1 Recruitment ........................................................................................ 83 3.3.2 Baseline characteristics of the cohort ...................................................... 84 3.3.3 Intra-rater reliability ............................................................................. 85 3.3.4 Inter-rater Reliability ............................................................................ 87 3.3.5 Regression modelling ........................................................................... 89 3 3.3.6 Normal Values ................................................................................... 106 3.4 Discussion ............................................................................................ 107 3.4.1 Findings & current evidence ................................................................ 107 3.4.2 Strengths .......................................................................................... 108 3.4.3 Limitations ........................................................................................ 109 3.4.4 Generalisability .................................................................................. 110 3.4.5 Future work ...................................................................................... 110 3.4.6 Conclusion ........................................................................................ 110 4 Childbirth and pelvic sensation ...................................................................... 111 4.1 Introduction ......................................................................................... 111 4.2 Materials and Methods ........................................................................... 111 4.2.1 Study design ..................................................................................... 111 4.2.2 Sample size....................................................................................... 112 4.2.3 Recruitment ...................................................................................... 112 4.2.4 Study entry ....................................................................................... 114 4.2.5 Clinical Visits ..................................................................................... 114 4.2.6 Retention .......................................................................................... 114 4.2.7 Demographic data .............................................................................. 115 4.2.8 Delivery data ..................................................................................... 115 4.2.9 Quantitative sensory testing ................................................................ 116 4.2.10 Pelvic organ prolapse ......................................................................... 117 4.2.11 Pelvic floor symptoms ......................................................................... 117 4.2.12 Statistical analysis ............................................................................. 118 4.3 Results ................................................................................................ 124 4.3.1 Recruitment ...................................................................................... 124 4.3.2 Retention .......................................................................................... 125 4.3.3 Baseline cohort characteristics ............................................................