Discussion of the evidence

• 1. What is the role of the CNS in the experience of CPP? Search Strategy: Pelvic pain (MeSH) AND CNS.

Since early pain studies of the hypothalamic pituitary axis in the late 1990s [3], interest has grown in the notion that the key to understanding CPP lies in the CNS rather than the pelvis. More recently studies have focused on the structure and function of the brain itself comparing pain patients to controls.

Two studies have examined changes in gray matter volume in women with CPP. As‐Sanie et al. used voxel‐based morphometry to demonstrate that a similar reduction in gray matter volume in brain regions associated with pain processing was seen in women with CPP, whether or not endometriosis had been demonstrated in the pelvis. Pain‐free women with and without endometriosis did not show any such reduction [4]. Tu et al. used a similar methodology to compare 32 women with primary dysmenorrhea and 32 pain‐free controls. Again, alterations in gray matter volume were observed in areas of the brain known to be involved in pain processing and these persisted throughout the menstrual cycle i.e. beyond the duration of pain [5]. The same group identified altered cerebral metabolism in pain associated regions in women with menstrual pain compared to pain‐free menstruating women [6].

Vincent et al. used functional magnetic resonance imaging (MRI) (which detects alterations in blood flow identifying activation and deactivation of specific regions within the brain) to examine responses to experimental pain in women with dysmenorrhea but no ongoing pelvic pain compared to controls. Again changes in response to experimental pain were observed in pain subjects throughout the menstrual cycle, not just during the painful period. Mean serum cortisol levels were lower in women with dysmenorrhea compared to controls and levels correlated with duration of symptoms. Physical but not mental quality of life was also lower for women with dysmenorrhea [7].

Stratton and Berkley reviewed the existing literature to explore what is known of the link between endometriosis (as a potential association with pelvic pain) and the CNS. It is clear that endometriotic lesions can establish their own nerve supply and that this could provide a two‐way interaction between the disease and the CNS. It seems clear therefore that in addition to treating pathologies known to be associated with CPP, a focus on the CNS may also open potential conceptual and therapeutic options in the understanding and management of CPP [8].

Two helpful reviews summarize the clinical situation well. Baranowksi describes the potential genesis of pelvic pain starting from a relatively benign initial trigger which in a predisposed individual may progress to involve multiple layers of dysfunction including alteration in the perception of physiological sensation, associated musculo‐skeletal tension particularly in the pelvic floor, autonomic dysfunction, and difficulty in functioning both physically and socially. This has been termed a complex regional pain syndrome [9]. Aslam et al. explores the concept of visceral hyperalgesia a condition which describes the hypersensitivity of other organs in the same region which can develop in response to pain arising from the pelvis, and can lead to dysfunction in those organs [10].

In clinical discussions with patients suffering from CPP, the notion that the CNS may be involved in the genesis of pelvic pain seems to resonate with sufferers. Women are often aware of the way in which their symptoms are affected by psychological factors or their menstrual cycle and are glad of a template for this discussion which avoids the dichotomy between an organic and a psychological cause for their pain, but rather promotes a conversation about influences and factors which could be amended.

The recognition of the impact that primary dysmenorrhea has on women’s lives as well as these primary research data which demonstrate its effect on the CNS, has led to the inclusion of dysmenorrhea as a CPP syndrome in the most recent IASP taxonomy [11].

• 2. In women with CPP how does the initial consultation influence outcome? Search Strategy: Pelvic pain (MeSH) AND consultation AND outcome.

In addition to the information included in the existing evidence‐based guidelines, this search identified two additional papers of interest. In a study by Verheul et al., 30 healthy women with menstrual pain participated in a study in which they were asked to imagine having severe symptoms and take part in a scripted consultation with a general practitioner. Subjects completed questionnaires to measure their anxiety and expectations of success following the General Practitioner (GP) consultation. They were randomized to receive a scripted communication style from their GP which was either warm and empathic or cold and formal. In addition the GP adopted an outlook with either a positive expectation of the future or an uncertain outlook. In this highly controlled study which involved simulated patients and female GPs only, results suggested that only a warm empathic style associated with a positive outlook was likely to reduce anxiety and help the patient anticipate benefit from treatment [12].

In a second paper which provides a helpful synthesis of existing qualitative studies and an exploration of the potential and limitations of combining qualitative data, Souza et al. describe the emerging themes in studies of the doctor–patient interaction concerning CPP. Using clear methodology they include seven studies in a metasynthesis and draw out key themes. First they examine the considerable impact of CPP on women’s lives and the extent to which it disrupts their ability to fulfill their roles, with consequent effects on employment and on their families as well as their own sense of fulfillment. They explore the concept of secondary gain demonstrating how the focus of care should be on quality of life as a whole rather than on the pain itself. Second, they highlight the importance placed by patients on finding an explanation for the pain and the strain placed on the doctor–patient relationship if a pathological cause cannot be identified. It is clear that the doctor has an important role in validating pain and needs to understand how the pain is impacting on the patient’s life and what her expectations are with regard to investigation and treatment. They discuss the limitations of the biomechanical model of disease to understand a symptom of this kind and provide very helpful food for thought for clinicians seeking to treat women with CPP [13].

• 3. What is the prevalence of musculo‐skeletal abnormalities in women of reproductive age with CPP? Search Strategy: Pelvic pain: etiology (MeSH) AND musculoskeletal pain (MeSH).

Somatic (body wall) pain is poorly taught and understood among medical practitioners. Routine assessment of women with pelvic pain would not traditionally include assessment of the musculo‐skeletal system. Assessment even by those with an interest in the field is hampered by a lack of standardized tests. However, prevalence studies suggest that musculo‐skeletal dysfunction either as a primary cause of pain or secondary to chronic pain is common among patients with CPP. In a retrospective study of 987 women attending a CPP clinic, 22% of women were recorded as having pelvic floor tenderness [14]. In a prospective study of 19 women with CPP by the same author, subjects were significantly more likely than healthy controls to have abnormal musculo‐skeletal findings such as asymmetric iliac crests (61% vs 25%) [15]. In a blinded study of 48 women, abnormal musculo‐skeletal findings and pelvic floor tenderness were found significantly more commonly in the 19 women with CPP than in the 29 pain‐free women [16, 17].

Although the evidence base in this field is poor, clinicians should consider the involvement of a physiotherapist in their initial assessment particularly where the pain is movement or posture related or examination reveals focal tenderness.

• 4. What is the sensitivity and specificity of laparoscopy in identifying the cause of CPP in women? Search Strategy: pelvic pain (MeSH) AND diagnostic laparoscopy AND specificity and sensitivity.

No trials have been performed which adequately answer this question, because of the challenge of identifying an objective measure against which to judge the sensitivity and specificity of diagnostic laparoscopy which has traditionally been seen as the gold standard in the diagnosis of CPP. Although endometriosis can be identified at laparoscopy, it can also be asymptomatic and it is therefore not always clear whether the endometriosis is indeed the cause of the CPP. Some variants of endometriosis such as deep infiltrating disease and adenomyosis, may not be visible at laparoscopy and therefore the correct diagnosis may be missed.

Given the uncertain value of diagnostic laparoscopy several recently published guidelines advocate the use of a therapeutic trial of hormonal treatment to test the possible diagnosis of endometriosis rather than the first line use of diagnostic laparoscopy. MRI and transvaginal ultrasonography also have a useful role in the diagnosis of adenomyosis, endometriomas, and nodular (particularly bowel related) endometriosis http://www.eshre.eu/Guidelines‐and‐Legal/Guidelines/Endometriosis‐guideline.aspx.

Adhesions can also be identified reliably at laparoscopy but again, it is not always clear that adhesions cause pain. Certainly it is far from clear that dividing adhesions reduces pain [18]. Other conditions such as hernia may be visible at laparoscopy but their relevance is yet to be established.

It is important to remember that diagnostic laparoscopy is not without risk, with an incidence of injury to bladder, bowel, or blood vessel of approximately 2.4 per 1000 of which two‐thirds will need laparotomy [19]. Before undergoing diagnostic laparoscopy women should understand not only that these risks exist but also that a cause of their pain may not be found. It is vital that when this happens it is clear to both clinician and patient that the failure to identify pathology does not mean that the pain does not exist.

In managing women with CPP, screening for sexually transmitted infections (STIs) should always be offered to sexually active women even if the STI is not ultimately thought to be the cause of the pain. Failure to detect and treat an STI may lead to future sub‐fertility and increased risk of ectopic pregnancy, and increases the risk of onward transmission.

• 5. Which methods of pain relief are safe and effective in reducing CPP? Search Strategy: pelvic pain (MeSH) AND analgesia (MeSH).

The literature regarding effective treatment for CPP is hampered by the difficulties of defining the condition which is being treated. Clearly, if a treatable component of the pain is identified, then drugs or interventions specific to that condition should be considered. The search described above yielded no high quality studies of analgesia for CPP. What is known is that laparoscopic utero‐sacral nerve ablation (LUNA) is ineffective in the management of CPP [20].

In line with the WHO pain ladder, patients with CPP should be offered paracetamol with or without non‐steroidal anti‐inflammatory drugs (NSAIDs) in combination, taken regularly unless contraindicated. Although there is no evidence concerning CPP directly, Cochrane reviews concerning the use of NSAIDs for dysmenorrhea, suggest that no particular NSAID is better than another and patient or clinician experience should lead the choice [21]. The addition of opiate based drugs such as codeine or tramadol can be helpful particularly if taken only occasionally for peaks of pain but care should be taken to avoid constipation and addiction.

Little evidence exists to support the use of complementary therapies in CPP, although if the patient finds them helpful and wishes to explore their use, this seems reasonable, provided the patient is aware of potential interactions with other drugs.

It can be difficult to know whether there is a neuropathic element to a patient’s pain although the description of pain as burning, aching, or stabbing may be suggestive of nerve involvement. If pain is not well controlled with conventional analgesia, it may be worth trying an adjuvant analgesic such as amitriptyline (particularly helpful if sleep disturbance is an issue), pregabalin, gabapentin, or duloxetine. Some clinicians have identified innovative methods to diagnose and treat neuropathic pain including nerve blocks and surgery, but as summarized in a useful review article, more evidence is needed before these can be recommended unanimously [22].

A recent systematic review attempted to determine the value of psychological treatments in the management of CPP, emphasizing the need to adopt a biopsychosocial model in understanding and treating pain. Only four studies of adequate quality were identified and the heterogeneity in their design and small size made it difficult to draw conclusions. However two of the papers reported three‐month [23] and 12‐month follow‐up [24] in a study using Mensendieck somatocognitive therapy which can be seen as a hybrid of physiotherapy and psychotherapy. Results were encouraging with a significant improvement in pain scores 12 months after treatment. Further research is needed to explore its use in other settings.

Several helpful evidence‐based guidelines on the use of adjuvant analgesics have been published in recent years (Box 5.2). The reader is referred to the NICE guidelines: Neuropathic Pain – Pharmacological Management [25]. This gives a simple algorithm for treatment and includes the important advice to avoid starting opiates for benign pain without the advice of a specialist pain team.