Changes in pain perception after pelvis manipulation in women with primary dysmenorrhea: a randomized controlled trial

Depósito de investigación de la Universidad de Sevilla https://idus.us.es/ Esta es la versión aceptada del artículo publicado en: Pain Medicine This is a accepted manuscript of a paper published in: Pain Medicine Pain Medicine (2014): 10 septiembre 2014 DOI: https://doi.org/10.1111/pme.12404 El acceso a la versión publicada del artículo puede requerir la suscripción de la revista. Access to the published version may require subscription. “This is a pre-copyedited, author-produced version of an article accepted for publication in [insert journal title] following peer review. The version of record [Pain Medicine, Volume 15, Issue 9, 10 September 2014, Pages 1455–1463] is available online at: Oxford University Press [https://academic.oup.com/painmedicine/article/15/9/1455/1892723] [https://doi.org/10.1111/pme.12404] Title: Changes in Pain Perception after Pelvis Manipulation in Women with Primary Dysmenorrhea: A Randomized Controlled Trial Authors and affiliations: Silvia Molins-Cubero, PT, DO,* Cleofás Rodríguez-Blanco, PT, DO, PhD,† Ángel Oliva-Pascual-Vaca, PT, DO, PhD,† Alberto M. Heredia-Rizo, PT, PhD,† Juan J. Boscá-Gandía, PT, DO,* François Ricard, DO* * Department of Physical Therapy, Faculty of Nursing, Physiotherapy and Podiatry, University of Sevilla, Sevilla, Spain † Madrid Osteopathic School, Madrid, Spain * Corresponding author: Cleofás Rodríguez-Blanco, Department of Physical Therapy. Faculty of Nursing, Physiotherapy and Podiatry, University of Sevilla, c/ Avicena s/n, Sevilla 41009, Spain. Tel: (+34) 954486528; Fax: (+34) 954486527; E-mail: [email protected]. Abstract Objective. This study aims to evaluate the immediate effect of a global pelvic manipulation (GPM) technique, bilaterally applied, on low back pelvic pain in women with primary dysmenorrhea (PD). Design. A prospective, randomized, double-blind, controlled trial. Setting. Faculty of Nursing, Physiotherapy and Podiatry. University of Sevilla, Spain. Methods. The sample group included 40 women (30 ± 6.10 years) that were divided into an experimental group (EG) (N = 20) who underwent a bilateral GPM technique and a control group (CG) (N = 20) who underwent a sham (placebo) intervention. Evaluations were made of self-reported low back pelvic pain (visual analog scale), pressure pain threshold (PPT) in sacroiliac joints (SIJs), and the endogenous response of the organism to pain following catecholamines and serotonin release in blood levels. Results. The intragroup comparison showed a significant improvement in the EG in the self-perceived low back pelvic pain (P = 0.003) and in the mechanosensitivity in both SIJs (P = 0.001). In the between group comparison, there was a decrease in pain perception (P = 0.004; F(1,38) = 9.62; R2 = 0.20) and an increase in the PPT of both SIJs, in the right side (P = 0.001; F(1,38) = 21.29; R2 = 0.35) and in the left side (P = 0.001; F(1,38) = 20.63;R2 = 0.35). There were no intergroup differences for catecholamines plasma levels (adrenaline P = 0.123; noradrenaline P = 0.281; dopamine P = 0.173), but there were for serotonin levels (P = 0.045; F(1,38) = 4.296; R2 = 0.10). Conclusion. The bilateral GPM technique improves in a short term the self-perceived low back pelvic pain, the PPT in both SIJs, and the serotonin levels in women with PD. It shows no significant differences with a sham intervention in catecholamines plasma levels. Key Words. Primary Dysmenorrhea; Manipulation Spinal; Pelvic Pain; Pain Threshold; Serotonin; Catecholamines. Introduction Primary dysmenorrhea (PD) is a common gynecological disorder in women of childbearing age [1,2]. PD is defined by several symptoms that precede menstruation, in the absence of any organic pathology, and lasting around 48–72 hours [2]. The most common symptom is pain in the lower abdomen that radiates to both thighs or to the lumbar-sacral region. Pain is usually accompanied by less frequent signs and symptoms, such as tiredness, headache, nausea, constipation, and diarrhea [3,4]. The prevalence of PD varies between 45% and 95% of women of childbearing age [4,5]. It is a common cause of absenteeism from work or school, thus interfering with daily life and with many social costs arising from this [5]. There have been many proposals for interventions for PD in the scientific literature. As pelvic pain seems to be mediated by prostaglandin factor 2Å~ [6], the most common therapeutic approach has been medical treatment that usually involves the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) or oral contraceptives [7]. On one hand, NSAIDs are peripheral inhibitors of prostaglandin synthesis [8]. On the other hand, oral contraceptives inhibit ovulation and, consequently, the endometrium reduces in thickness thereby diminishing prostaglandin synthesis [7]. The efficiency of these treatments varies between 17% and 95% [4]. However, pharmacological treatment may involve some adverse side effects, like gastrointestinal bleeding, which increases their intolerance for some patients [4,9]. Hence, it is common for women to demand new and alternative therapeutic tools with less perceived associated risks [10]. Previous research has analyzed the effects on pelvic pain perception arising from PD through alternative therapies such as: 1) continuous low-level topical heat at hypogastric level [11]; 2) acupuncture [12–14]; 3) transcutaneous electrical nerve stimulation (TENS) and interferential current [15]; 4) homeopathy [16]; 5) Chinese herbal medicine [17]; 6) acupressure [18,19]; and even 7) low fat diets [20,21]. Many of these therapies have proven to have a positive impact on pain. However, these results are not conclusive enough to recommend their use routinely, due to poor methodological designs in some cases [10,22]. Several studies have evaluated the efficacy of spinal manipulative techniques on women with PD [23–26]. Spinal manipulation (SM) has proven to have some influence on pain perception and menstrual cramps, and also on plasma levels of some chemical mediators of pain [26–28]. Even though there are no conclusive observations to prove a positive effect of SM on pain associated with PD, there is a lack of agreement on which spinal region needs to be manipulated and on the techniques that may be most effective. Hence, there is some need to develop new studies in this field [29]. Holtzman et al. [25]. proposed that SM should be directed to specific restrictions in the lumbar-sacral spine (L5-S1) to alleviate pain associated with PD. Hypothesis The global pelvic manipulation (GPM) technique, bilaterally applied in women suffering from PD, improves pain perception on low back pelvic region and has a positive impact on the endogenous response of the organism to pain (catecholamines and serotonin release in blood levels). Objective Based on the neurophysiologic effects of SM techniques [30], the main aim of the study is to assess the immediate effects of a GPM technique in low back pelvic pain perception and in several nociceptive biomarkers in subjects with PD. Materials and methods Design and Randomization Procedure A randomized, by means of a randomized number table designed by an Internet website (http://www.randomized.org), and double-blind controlled clinical trial was conducted. The randomization sequence was guarded by an external consultant who guaranteed its concealment from all participants in the study: subjects, evaluators and therapist in charge of the interventions. Participants One hundred (N = 100) participants who had a history of low back pain and medical diagnosis of PD by a gynecologist, excluding any other gynecological pathology, were recruited for the study. The clinical records were selected from the main researcher’s practice. Sixty women (N = 60) were excluded from the study; 37 (N = 37) did not meet the inclusion/exclusion criteria, 14 women (N = 14) refused participation, and nine (N = 9) of them were excluded for reasons related mainly to fear to blood extraction or home address changes. During the allocation phase, 40 (N = 40) subjects who enrolled the study were distributed into two groups (N = 20). No losses to follow-up were recorded during data collection and analysis phases [31] (Figure 1). Established inclusion criteria were: 1) age between 18 and 50 years old; 2) diagnosis of PD according to the Primary Dysmenorrhea Consensus Guideline [32]; 3) regular menstrual cycle (28 ± 7 days); 4) menstrual pain of moderate or severe intensity (over 50 mm in the visual analog scale [VAS]); and 5) subjects who gave the informed consent. Exclusion criteria were the following: 1) to have an intrauterine device; 2) being diagnosed as suffering from secondary dysmenorrhea; 3) previous gynecological interventions; 4) contraindications to the GPM technique; 5) having received previous manipulative treatment within the 2 months before the beginning of the study; and 6) showing any stress or fear of SM. Sampling Process and Sample Size The subjects were selected according to nonprobabilistic convenience sampling techniques. The sample size was based on a pilot study [33], using the software “tamaño de la muestra 1.1”® (Hospital Universitario San Ignacio, Bogotá, Colombia). Taking into account a one-tailed hypothesis, the intergroup difference being of 20%, for an α value of 0.05, a variability of 15%, a desired power of 90%, and for an expected average of 25% in the experimental group (EG) and of 5% in the control group (CG), a sample size of 20 subjects per group was necessary. The final sample group consisted of 40 women with PD with a mean age of 30 ± 6.10 years (19–48). They were divided into an EG (N = 20) and a CG (N = 20). The study received approval and was designed conformed to the guidelines of the Institutional Ethical Committee. It has been registered in the Australian and New Zealand Clinical Trials Registry with registration number ACTRN12611001195943. Blinding All participants were informed of the general aspects of the study with the informed consent form (possible benefits, risks, precautions and side effects of the assessments, and the interventions). They were told before randomization that different types of treatments will be compared in the study. Subjects and evaluators who collected or analyzed data remained unaware of the treatment allocation group and the specific aims of the study to guarantee participant and outcome assessor blinding. The therapist in charge of the manipulation (interventor) did not participate in the assessment protocol. Measures were also taken to ensure that the interventor remained unaware of the treatment allocation group (interventor blinding). Study Protocol Subjects were contacted by phone. Once it was confirmed that they qualified under the inclusion/exclusion criteria and their willingness to participate, they were referred to the study setting the first day of the menstrual cycle. Then, the subject completed the informed consent paper, which was prepared in accordance with the Declaration of Helsinki (version 2008), and filled the personal and clinical data form. The measurement protocol took place in a room equipped with a treatment table and a steady temperature between 18°C and 21°C. All evaluations were performed in both groups before and after the intervention in the following order. Assessment of Low Back Pelvic Pain A VAS was used to measure self-reported pain. VAS is considered to be a validated, effective, accurate, sensitive, easy to use, and reproducible method to assess acute and chronic pain [34]. The subject marked on the VAS the current intensity of low back pelvic pain. The result was expressed in millimeters (mm), ranged from 0 mm to 100 mm. Assessment of Pressure Pain Threshold (PPT) in Sacroiliac Joints (SIJs) PPT is defined as the minimum amount of pressure needed to evoke discomfort or pain [35]. A digital dynamometer (PCE, FM model 200, Meschede, Germany) was used to which makes it difficult to find solid conclusions. In regard to plasma levels of nociceptive biomarkers, Degenhardt et al. [27] found no significant changes for serotonin levels after osteopathic manual therapy (OMT) in subjects with low back pain. This result suggests that the effects of the OMT without applying HVLA techniques may not be mediated by the serotonergic pathway but probably by endogenous opioids and cannabinoids. On the contrary, Skyba et al. [28] demonstrated in an animal model that joint manipulation augments the serotonin concentration, which can produce analgesia through the descending inhibitory pathway. When comparing between-groups, we observed a significant increase of serotonin concentration in the EG. It may be reasonable to state that this result is due to the decrease found in the serotonin level in the CG (14.93 Å} 36.58 ng/mL), because the increase in the EG level was small (4.98 ± 22.51 ng/ mL). We find no definite explanation for these results in the CG. Some studies have shown no statistical changes on nitric oxide concentration blood levels after alternative therapies (yoga and acupressure) in women with PD [51,52]. It remains an issue for future studies to complement the present evaluations with the assessment of nitric oxide levels after SM. It may help to get a better understanding of the clinical effect of manipulative techniques in PD. Limitations The study has certain limitations. First, the subject’s intake of NSAIDs and/or cyclooxygenase-2 specific inhibitors was not controlled. This could be a plausible explanation to understand the baseline intergroup differences in the perceived pain. It could be also argued that the intake of oral contraceptives, which has been related to pelvic pain alleviation [7], was higher in the EG (25% of subjects). Low-back pelvic pain seems to be associated with hypermobility, strain of the joints, and body mass index [50]. Participants’ height and weight were not measured in this trial. Unlike previous research [23,25], no evaluation of specific lumbar-sacral motion restrictions was performed either. Second, the findings must be cautiously interpreted because the study has only assessed immediate effects. Long-term results should be evaluated in future studies [53]. Finally, the measurement of catecholamines and serotonin plasma level is complex because it is influenced by food intake, stress, and patient position, and it shows a circadian rhythm [54]. Subjects were always placed during measurements in a sitting position, and they were at rest between each blood extraction. The study was always performed between 8:00 PM and 9:00 PM to avoid influencing the baseline levels. However, if any woman had a fear of SM or blood extraction and failed to report such feeling, catecholamines levels may have been altered in the postintervention evaluation. Conclusions The GPM technique, bilaterally applied to women with PD, appears to increase significantly the PPT in the SIJ and reduce the self-reported low–back pelvic pain in a short term. Regarding the plasma levels of chemical modulators of pain (catecholamines and serotonin), the GPM technique increases serotonin levels, with a small effect size. It shows no statistical significance in comparison with a sham (placebo) intervention for catecholamines plasma levels. References 1 Kennedy S. Primary dysmenorrhoea. Lancet 1997;349:1116. 2 Mish PC, ed. Webster’s Ninth New Collegiate Dictionary. Springfield, MA: MerriamWebster Inc.; 1986. 3 Dawood MY. Dysmenorrhea. 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