Efectividad de un programa de educación en neurociencia del dolor en mujeres con vulvodinia y correlaciones con la conectividad cerebral estudiada mediante resonancia magnética funcional

Resumo

Effectiveness of a Pain Neuroscience Education Program in Women with Vulvodynia and Correlations with Brain Connectivity studied by Functional Magnetic Resonance: a single case experimental design Background: Vulvodynia is a painful condition that affects 8-10% of women of all ages and is characterized by pain in the vulva that occurs spontaneously or provoked, often by sexual intercourse. Vulvodynia has a negative effect on the quality of life of women and their partners, and is associated to a significant personal, economic and social burden. Internationally, there is no general consensus on vulvodynia treatment algorithms, and recommended guidelines are based primarily on expert opinion and a limited number of clinical trials. Education in pain neuroscience is an emerging strategy that is offering promising outcomes in the management of chronic pain. The objective of this thesis is to study the therapeutic effectiveness of this treatment in patients with vulvodynia and dyspareunia and if this type of treatment is able of modifying brain connectivity patterns. Several randomized controlled trials (RCTs) have investigated the efficacy of pain neuroscience education (PNE) in various pain conditions. There have also been published several systematic reviews that have shown consistent evidence that PNE has a positive effect on pain and disability. The latest systematic review published in 2019 has shown that PNE can reduce pain, disability, catastrophism and kinesiophobia in the short and medium term, although the heterogeneity of the outcomes is very wide. However, so far no study has been conducted implementing PNE in the treatment of vulvodynia and whose objectives have been to reduce pain and its associated disability. Study design: A single case type AB experimental design has been used, in which the measurements have been done in a first phase divided into 2 times (A1 and A2), an intermediate phase (treatment phase), with a simultaneous intervention in 15 patients and finally a second phase of outcomes assessment, also divided into 2 times (B1 and B2). The thesis presented consists of two studies: Study 1 is a prospective controlled study of the effects of an intervention program based on PNE in women with vulvodynia and Study 2 analyses the effects of this treatment on brain connectivity using functional magnetic resonance imaging (fMRI). Patients: 15 women with vulvodynia and dyspareunia were recruited, whose age ranged from 21 to 54 years and with an average of 6 years of evolution of the pain condition. Methods: Study I consisted of an intervention program based on PNE and gradual exposure. Each patient received an average of seven educational sessions over approximately 6-8 weeks, plus follow-up sessions over approximately 1 year. After the educational sessions, most of the women received recommendations on strategies to facilitate their desensitization. In study 2, three fMRI and structural MRI (DTI) were performed on each patient: 1st MRI at baseline at the start of the study, at time A1 (MRI 1); 2nd MRI before the intervention program (MRI 2) in the time A2 and a 3rd MRI at follow-up (MRI 3). A full study was obtained in 14 of the 15 patients, as one patient dropped out of the study during the intervention period. The time from MRI 1 (A1) to MRI 2 (A2) was 53 days, from MRI 2 (A2) to MRI 3 (B1) 366 days and from MRI 3 (B1) to the end of the study (B2) 225 on average. Measurements: To assess the treatment efficacy in study I, the following variables were analysed: (1) Variables from the clinical interview in 2 times A1 and B1. (2) Variables from the online questionnaire that the patients have completed weekly from the beginning of the study [A1] until the final assessment of the follow-up [B2]. (3) Questionnaires of pain and disability in 3 times: at beginning [A1] matching with the 1st MRI, after the waiting period and 2nd MRI [A2] and finally in the assessment phase, matching with the 3rd MRI [B1]. (4) Maps of pain and allodynia [A1, B1]. (5) Quantitative sensory testing [A1, A2 and B1]. In study II, the following studies were carried out: 1) Brain functional connectivity MRI study through independent component analysis (ICA). (2) Study of functional connectivity through the analysis of regions of interest (ROIs). (3) Study of the correlations between clinical variables and the global connectivity of each network and the connectivity of each pair of nodes (4) Discriminant analysis to assess the predictive value of brain connectivity in the pain experienced during the MRI (5). Structural connectivity study using the diffusion tensor imaging (DTI). Outcomes: It has been observed that a treatment program based on PNE is effective in the treatment of pain, obtaining a complete suppression of pain and allodynia in the majority of women with vulvodynia and dyspareunia. This treatment reduced anxiety, depression, catastrophism, kinesiophobia, miscognitions related to pain, interference of pain in the patient’s life and disability and improved the quality of sexual life in women with vulvodynia. The treatment carried out significantly reduced the areas of pain and allodynia both in the vulva and in the rest of the body regions. It has also been observed that the therapeutic effects were maintained beyond 12 months. Pressure pain and allodynia thresholds were significantly reduced at each of the six anatomical points of the vulvar mucosa studied. No differences were found in the tests of conditioned pain modulation (CPM effect) before and after the treatment and although the values of the temporal summation ratio (WUR) seem to indicate an improvement in pain intensity, due to the number of patients in whom there were no data after treatment, the results are not considered relevant. It has been observed that this treatment is able of modifying brain connectivity patterns in patients with vulvodynia and dyspareunia. After treatment, a significant increase in functional connectivity was observed between the anterior and posterior components of the Default Network (DMN). A significant decrease in functional connectivity was observed between the Right Anterior Insula (raINS) and the Posterior Cerebellum (vermis), which is part of the salience processing circuit. A correlation was observed between the global connectivity of some brain networks and different clinical variables both before and after the intervention. A correlation between pain and visual network (VN) nodes connectivity was observed. The decrease in pain in patients with vulvodynia after treatment was associated with a significant decrease in the connectivity of the VN nodes, of this network with sensorimotor network nodes (SMN) and with nodes of the salience network (SN). The discriminant analysis showed that the connectivity between the nodes of the DMN, SN and the Dorsal Attention Network Frontoparietal is able to predict in 88.9% of the cases whether or not the patient experienced pain during the fMRI study. No change in structural connectivity was observed by DTI analysis before and after treatment, nor any correlation with clinical variables.