Painful periods

Period pain

Period or menstrual pain is also referred to as dysmenorrhoea, and is usually further classified as primary (no evidence of pathology) or secondary (linked to pathology such as endometriosis). Menstrual pain affects about 60% of women who are menstruating [6], although up to 90% of adolescents can be affected [2]. For a proportion (estimate 2-28%), their pain is severe and distressing with a negative impact on many aspects of life, including missing school/work, reduced physical activity, disrupted sleep and reduced quality of life [5].

Why were we interested in menstrual pain?

We were interested in putting menstrual pain severity under the spotlight, because of the association with other painful conditions like low back pain, fibromyalgia, and irritable bowel syndrome, as well as with psychological conditions [5]. We wanted to try and understand the interactions between menstrual pain severity and tissue sensitivity and examine if musculoskeletal pain explained some of the association.

So what do we know about menstrual pain and tissue sensitivity?

In females with severe menstrual pain, heightened tissue sensitivity in response to different stimuli (pressure, pinch, thermal) is found locally (in the low abdomen/low back) and at sites distant from typical pain referral sites [4]. Sensitivity changes that occur in viscera and in deep tissues like muscles are evident around menses, but also across the menstrual cycle [4].

What about other factors?

Factors that can predispose to menstrual pain or dysmenorrhea include: low body mass index, earlier menarche (< 12 years), longer menstrual cycles, heavy menstrual flow, premenstrual syndrome, sterilisation, clinically suspected pelvic inflammatory disease, and psychological symptoms [5]. Associations between primary dysmenorrhea and women’s age, parity, oral contraceptive use, stress levels and family history are also reported, while the role of modifiable factors including cigarette smoking, diet, obesity, depression, and sexual abuse are less clear [5].

Our study

We tested the association between menstrual pain severity and measures of cold and pressure pain sensitivity, adjusting for potential confounding variables (number of musculoskeletal pain sites, oral contraceptive use, smoking, physical activity, body mass index, psychological distress, and sleep) [8].

Methodology

We used a cross-sectional design to look at the association between menstrual pain severity and sensitivity to pressure and cold stimuli in a community sample of young women (n=432) from the Western Australian Pregnancy Cohort (Raine) Study. This community sample was a good size and captured a representative group of young females making the findings more generalizable.

Menstrual pain severity and oral contraception use and data about multisite pain and other potentially confounding variables of interest were measured from questionnaires already planned for collection at age 20 and 22 year follow ups.

A visual analog scale (VAS; range from 0 (none) to 10 (unbearable)) was used to measure menstrual pain severity at both 20 and 22 years over the 3-year period, with three groups created: 1) no pain/mild pain (VAS 0-3), 2) at least moderate pain at a minimum of one of the two time points (hereafter named ‘mixed’, 3) severe pain (VAS 8-10).

We extended the data capture by using standardised quantitative sensory testing (QST) protocols that allowed us to measure sensitivity to cold and pressure [1]. Pain threshold for cold sensitivity was tested at the wrist (dorsum) and for pressure sensitivity at four sites (wrist, the trapezius muscle along the neck, the low back and the lower leg).

What we found

Severe and ‘mixed’ menstrual pain were positively associated with heightened cold pain sensitivity (distant from menstrual pain referral site) and pressure pain sensitivity (local to menstrual pain referral site). These associations remained after adjusting for all covariates including multisite musculoskeletal pain.

Severe menstrual pain was significantly associated with a predicted cold pain threshold of 7.8 °C (95 % CI 3.1-12.4 °C) lower (i.e.; perceiving cold pain sooner or at a higher temperature) among those with severe pain and 4.3 °C (1.7-7.0 °C) lower among those with mixed pain, compared to the females with no pain or mild pain.

Severe menstrual pain and mixed pain were associated with lower pressure pain thresholds (i.e. more pressure sensitive) at the lumbar spine (severe: -135.6 kPa (-206.1, -65.1); mixed: -61.7 kPa (-100.3, -23.0)).

What it means

We propose that severe menstrual pain may provide a sufficient viscero-visceral/viscero-somatic nociceptive input of a cyclic nature that effectively ‘primes’ the nervous system [3]. We speculate that this ‘priming’ may translate as biologic stress. Prolonged stress can alter central regulatory systems such as the HPA-axis with resultant dysfunction, including blunted cortisol responses [7]. Such dysfunction can trigger a cytokine-mediated sickness response, and at least partly explain the more widespread tissue sensitivity to cold and pressure (a bit like having the flu, which also activates the immune system with widespread sensitivity) and further increase susceptibility to addition nociceptive inputs.

Where to next?

We need longitudinal data to help us better understand the causal relationships underlying these associations and to establish trajectories between menstrual pain severity and other somatic pain conditions. Our data highlight the need for innovative management approaches to attenuate the negative impact of severe menstrual pain in young women.

Acknowledgements: Raine Study participants, RaineStudy Team, University of Western Australia, the Raine Medical Research Foundation, the Telethon Kids Institute, the Women’s and Infant’s Research Foundation, Curtin University, Edith Cowan University, and funding from NH&MRC, Lions Eye Institute and Safework Australia

About Helen Slater

Helen Slater Curtin UniversityHelen is a clinical researcher and physiotherapist at the School of Physiotherapy and Exercise Science, Curtin University. She’s interested in all things pain but especially findings ways to get evidence about pain into real world clinical settings. Along with colleagues, she researches models of care for people living with musculoskeletal pain; explores ways to use health policy to lever the best evidence into clinical practice; upskills consumers with pain and health professionals about pain; and investigates the ways in which the same clinical problem can present so differently in each individual. She acknowledges the fab team who all worked on bringing together this piece of work. She’s reckons she’s really lucky to work with lots of collegial, really smart, fun people.

References

[1] Backonja M M, Attal N, Baron R, Bouhassira D, Drangholt M, Dyck P J, Edwards R R, Freeman R, Gracely R, Haanpaa M H, Hansson P, Hatem S M, Krumova E K, Jensen T S, Maier C, Mick G, Rice A S, Rolke R, Treede R D, Serra J, Toelle T, Tugnoli V, Walk D, Walalce M S, Ware M, Yarnitsky D, Ziegler D. Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus. Pain 2013;154(9):1807-19.

[2] Berkley K J. Primary Dysmenorrhea: An Urgent Mandate,. PAIN Clincal Updates, Vol. VOL XXI IASP, 2013.

[3] Giamberardino M A, Costantini R, Affaitati G, Fabrizio A, Lapenna D, Tafuri E, Mezzetti A. Viscero-visceral hyperalgesia: characterization in different clinical models. Pain 2010;151(2):307-22.

[4] Giamberardino M A, Tana C, Costantini R. Pain thresholds in women with chronic pelvic pain. Curr Opin Obstet Gynecol 2014;26(4):253-9.

[5] Ju H, Jones M, Mishra G. The prevalence and risk factors of dysmenorrhea. Epidemiol Rev 2014;36(1):104-13.

[6] Ju H, Jones M, Mishra G D. Premenstrual syndrome and dysmenorrhea: symptom trajectories over 13 years in young adults. Maturitas 2014;78(2):99-105.

[7] Paananen M, O’Sullivan P, Straker L, Beales D, Coenen P, Karppinen J, Pennell C, Smith A. A low cortisol response to stress is associated with musculoskeletal pain combined with increased pain sensitivity in young adults: a longitudinal cohort study. Arthritis Res Ther 2015;17:355.

[8] Slater H, Paananen M, Smith AJ, OʼSullivan P, Briggs AM, Hickey M, Mountain J, Karppinen J, Beales D. Heightened cold pain and pressure pain sensitivity in young female adults with moderate-to-severe menstrual painPain. 2015 Dec;156(12):2468-78

Comments

  1. Helen Slater says

    John, Thank you for your comments. In our paper (the hyperlink is provided as reference 8 above) we elaborate on what biological mechanisms might be involved – albeit necessarily brief. One of your papers [Lyon P, Cohen M, Quintner J. An Evolutionary Stress-Response Hypothesis for Chronic Widespread Pain (Fibromyalgia Syndrome)
    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21692974%5D also provides an interesting interrogation of the ‘whole-organism stress response’ in the context of evolutionary biology and widespread sensitisation. If, and how, this might underlie the sensitisation evident in young women experiencing severe menstrual pain described in our paper requires more exploration with high quality longitudinal studies. Plenty to keep us busy and it’s important to have such longitudinal data to test various hypotheses. Thanks again for your comments.

  2. Alison Lingwood says

    Hi Helen, So what is it the these group of women with heightened immune response have in common ? Could it be their own conscious/ unconscious view of themselves as a woman, in today’s challenging society, is a large part of the trigger : attack on the self ? I would like to suggest it is.

    Helen Slater Reply:

    Alison, thank you for your comment. Our data do not provide the answer to this question. There are many factors that are likely to influence tissue sensitivity – these are likely complex; and the interactions between factors complex too.

  3. I also agree that there is a stress hormone interaction at play. It would be interesting to test for diurnal cortisol. There is also evidence to show estrogen dominance (too high of a ratio of estrogen as compared to progesterone) as a source of these symptoms. It may be valuable to test hormone levels, as well. On the note of having other widespread lowered pain thresholds, there was some talk/survey in another group about whether women were experiencing increased hip pain in the week prior and the week of menstruation. The consensus was an overwhelming, yes. And I would agree, anecdotally, my pain levels go up in hip, shoulder and SIJ at that time. Is there a stress response creating increased cortisol, inflammatory response, or estrogen dominance at play? Would love to hear more on this as it comes.

    Helen Slater Reply:

    Tianna, Thank you for your comments. Please see my comment to Alyssa above. That may be of interest to you. Helen

  4. Had to suffer with period period pain till my mid 40’s then I was diagnosed with adenomyosis. My pain then made sense to me and I am able to manage it. Till then every medical officer I went to treated me as if I was overly sensitive to normal period pain, basically told me to go away- not sure how my comment helps your study , but any work in this area is a positive.

    Helen Slater Reply:

    Karen, thank you for sharing your story. You have captured one of the ongoing problems in this area. While periods are normal for females across part of our life span, and pain with periods is common (and accepted by most as ‘normal’!), when severe, we need to find better ways to help females treat and manage it, including identifying specific causes where appropriate. Helen

  5. Helen, would you consider testing diurnal cortisol rhythms in this cohort in order to see if there is support for your prolonged pain -> ongoing physiological stress response -> HPA dysfunction with reduced cortisol output/response to demand -> increased sensitivity to cold and pressure theory? Certainly blunted cortisol responses is something I see clinically quite frequently in my chronic pelvic pain patients. Fascinating.

    Helen Slater Reply:

    Thanks you Alyssa,
    Yes! This is something we plan to consider. There is some data about menstrual pain and cortisol already. For example, Vincent et al. 2011 (http://www.ncbi.nlm.nih.gov/pubmed/21524851) showed that the longer the
    duration of severe menstrual pain (dysmenorrhea), the greater the suppression of the woman’s HPA ( biomarked as a reduction in cortisol). Some of our co-authors have also looked at the association between cortisol responses and musculoskeletal pain (alone and MS pain plus increased pain sensitivity) in the Raine cohort (see Paananen et al. Arthritis Research & Therapy. 2015;17:355; http://www.ncbi.nlm.nih.gov/pubmed/26654189). They found a hypo-responsive HPA axis at age 18 years was associated with MS pain at 22 years in young females with increased pain sensitivity. We do need to explore these relationships further – it is probably also worth looking at my reply to Dr Quintner’s comment – his paper would be of interest to you too. Helen

  6. No mention of cancer. I consistently had severe period pain with nausea, starting at 9 years old. Then I got a diagnosis of ovarian cancer at 22. I think researchers need to look for correlation between pain and any sort of lesions or indications of cancer developing. It’s already known that girls who get their periods early are at risk for cancer. So what can be done to prevent it?

    Helen Slater Reply:

    Lisa, you raise a really important point. Like all pain, it is always critical to try and ensure that any serious pathology or condition (like cancer) is picked up as early as possible and appropriate treatment given. This should be a priority for clinicians, with appropriate early on-referral if relevant. In our study, the young females were from a big community sample and not coming to see us because of their pain, rather this was just one aspect of a lot of information we gathered. Not all pain means something serious (life-threatening like cancer) is wrong. The trick is to be able to pick what is and what isn’t, because the treatments differ! Getting the right treatment at the right time, by the right team is the main goal.

  7. John Quintner, Rheumatologist says

    Helen, congratulations to you and the team for undertaking this most important study. Would you provide a brief summary of what is known about the possible mechanism(s) of menstrual pain? As you mention, the link with conditions such as Chronic Widespread Pain (fibromyalgia) suggests that what is happening in the uterus each month constitutes a significant biological stressor to many women in this age group.

    Helen Slater Reply:

    John, Thank you for your comments. In our paper (the hyperlink is provided as reference 8 above) we elaborate on what biological mechanisms might be involved – albeit necessarily brief. One of your papers [Lyon P, Cohen M, Quintner J. An Evolutionary Stress-Response Hypothesis for Chronic Widespread Pain (Fibromyalgia Syndrome)
    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21692974%5D also provides an interesting interrogation of the ‘whole-organism stress response’ in the context of evolutionary biology and widespread sensitisation. If, and how, this might underlie the sensitisation evident in young women experiencing severe menstrual pain described in our paper requires more exploration with high quality longitudinal studies. Plenty to keep us busy and it’s important to have such longitudinal data to test various hypotheses. Thanks again for your comments.