The impact of primary dysmenorrhoea on pain perception, quality of life, and sleep in young healthy women.

Abstract
Primary dysmenorrhoea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynaecological condition that affects between 45 to 95% of menstruating women. Despite the high prevalence, dysmenorrhoea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. The overall purpose of this thesis is two-fold: first, to contribute knowledge about the impact and consequences of recurrent severe menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhoea, and secondly, to investigate day-time and night-time treatment of recurrent primary dysmenorrhoeic pain. For this thesis, I completed five separate studies on three different groups of young, otherwise healthy women with a history of severe primary dysmenorrhoea, and age-matched controls without dysmenorrhoea. The first two studies, presented in Chapter 2, addressed the question of whether women with primary dysmenorrhoea are hypersensitive to experimental pain. I used clinically-relevant experimentally-induced muscle pain stimuli (intramuscular injection of hypertonic saline and ischaemia) in referred and non-referred sites of menstrual pain, at different phases of the menstrual cycle. Women with dysmenorrhoea, compared to women without dysmenorrhoea, had increased sensitivity to deep-muscle pain both within the area of referred menstrual pain and at a remote pain-free site. Further, the increased muscle pain sensitivity was evident even in phases of the menstrual cycle when women did not have menstrual pain, illustrating that the changes in pain perception extend outside of the painful menstruation phase. These findings suggest that women with dysmenorrhoea show long-lasting changes in pain processing possibly because of the recurrent dysmenorrhoeic pain. A secondary aim of the study presented in Chapter 2a, was to determine the impact of menstrual cycle phase on experimentally-induced muscle pain sensitivity in women with and without primary dysmenorrhoea. My results suggest that menstrual cycle phase has no effect on pain sensitivity in either group of women. As part of my studies, I investigated the impact of dysmenorrhoeic pain on quality of life and mood. I found that women with dysmenorrhoea had a significantly reduced quality of life (Chapter 3) and poorer mood (Chapter 2a and Chapter 5), during menstruation compared to their pain-free follicular phase, and compared to the menstruation phase of the pain-free control women. These data highlight the negative impact that primary dysmenorrhoea has on young women, for up to a few days every month. Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed as the first-line therapy for menstrual pain. Yet, severe dysmenorrhoeic pain is often poorly managed, especially at night, when the pain likely disrupts sleep. I conducted two studies investigating the effectiveness of diclofenac potassium, a readily-available NSAID with a low side-effect profile, compared to placebo, in alleviating severe primary dysmenorrhoeic pain across the day (Chapter 4), and during the night (Chapter 5). I also investigated the effectiveness of diclofenac potassium in improving subjective and objective sleep quality (Chapter 5). I found that the daily recommended dose (150 mg) of diclofenac potassium, administered at three timepoints across the first 24 hours of menstruation, significantly reduced perceived menstrual pain, compared to placebo. I confirmed that dysmenorrhoeic pain reduces polysomnographic and subjective measures of sleep quality compared with the pain-free follicular phase. I also showed, for the first time, that diclofenac potassium is effective, compared to placebo, in alleviating nocturnal pain, along with restoring subjective sleep quality and polysomnographic measures of objective sleep quality in women with severe primary dysmenorrhoea. My studies have addressed several gaps in the knowledge about primary dysmenorrhoea. I have shown that women with primary dysmenorrhoea are hypersensitive to deep muscle pain, supporting the hypothesis of other researchers that the recurrent menstrual pain experienced by these women is associated with central sensitisation, and may predispose women with primary dysmenorrhoea to other chronic painful conditions. Therefore, limiting the monthly noxious input into the central nervous systems of these women, by means of effective treatment of dysmenorrhoea, may improve their long-term health. The research presented in this thesis further highlights the efficacy of diclofenac potassium in relieving not only day-time and night-time dysmenorrhoeic pain, but also in restoring objective and subjective pain-induced sleep disturbances in women with dysmenorrhoea. Further, my research has shown that dysmenorrhoeic pain has an immediate negative impact on quality of life and mood during menstruation. The results of this thesis show the multi-factorial impact of dysmenorrhoea and should stimulate further research about the long-term benefits of effective treatment of menstrual pain.
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