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Abstract

Chronic pelvic pain (CPP) is a prevalent disorder amongst women. The physiology of CPP is attributed to various neurophysiological mechanisms and endometriosis, adenomyosis, chronic infection and functional disorders such as irritable bowel syndrome or interstitial cystitis are all diseases which fall under the umbrella term of CPP. CPP and its associated multitude of causes can affect perioperative care through several mechanisms. Patients with CPP may be more likely to experience significant pain in the perioperative setting and preoperative pain can be a predictor of post-operative pain. Thus, optimisation of CPP prior to the perioperative period is an important consideration. Currently limited and conflicting evidence exists regarding the peri-operative pharmacological analgesia. The various aetiologies of CPP and patient medical history result in the inability to generalise one analgesic regime. Areas of further research includes neuromodulation techniques, genomic and proteomic biomarker studies and the applicability of artificial intelligence.

Keywords

Chronic pelvic pain perioperative endometriosis dysmenorrhea dyspareunia

Introduction

In Australia, one in five women and one in twelve men are affected by chronic pelvic pain (CPP) sometime in their life. However, despite the prevalence of CPP within our society, it is a severely understudied condition with a current lack of clarity existing around the perioperative management of CPP. While current traditional approaches to managing CPP primarily involves medical or surgical therapy, the only moderate improvement in long term pain highlights the need for further exploration into alterative management options.¹ This review aims to highlight the causes of CPP, the challenges in managing CPP and suggest alternative treatment options for managing this complex condition.

CPP is defined as pain emerging from the pelvis and lasting for more than 6 months. It is often accompanied by low mood, pessimism and poor sexual experiences. The patient population suffering from CPP are also vulnerable due to multiple physical and psychological comorbidities. CPP is also associated with lower urinary tract, bowel, sexual or gynaecologic symptoms.² The most common diagnoses associated with CPP are irritable bowel syndrome (26.2%), ovarian cysts (20.8%), stress (19.5%), endometriosis (14.8%), cystitis (14.1%) and back problems (13.45%).³ CPP causes can affect perioperative care through several mechanisms; however, it most clearly affects aspects of analgesic management. Additionally, surgical therapy can only be appropriately scheduled following an accurate diagnosis. However, as the underlying diagnosis is often non-life threatening in nature, the peri-operative period is highly variable from weeks to months, with endometriosis-related surgeries often generally classified in Australia as elective category three surgeries with a waitlist time of up to a year.⁴

Chronic pelvic pain syndrome (CPPS) is defined as a syndrome encompassing common urological and gynaecological diseases. Symptoms appear to arise from interactions between psychological factors and impairment in immune, neurological and endocrine systems.⁵ When defining CPPS, one should ensure that symptoms are unrelated to menstruation, pregnancy, trauma or previous surgeries.⁵ The similarities between CPP and CPPS are that both should last more than 6 months and be severe enough to affect functionality of patients.⁶

Societal impact of CPP

The societal impact of CPP is often under-recognised. In a study, Pitts et al.⁷ data on 1983 Australian women aged 16–49 years who were still menstruating and sexually active was collected. The prevalence was 71.7% for dysmenorrhoea, 14.1% for dyspareunia and 21.5% for other CPP.⁷ However, only 34.2% of women who reported pain sought medical advice. Additionally, men aged between 25 and 50 years old who experience CPP, often hesitate to seek treatment.

A systematic review by the World Health Organisation, Latthe et al.⁸ showed that CPP was an important cause of morbidity in women. However, the condition was being neglected due to lack of epidemiological data.

A multitude of CPP patients experience yellow-flag symptoms such as depression, anxiety, extended rest and isolation due to fear of pain, substance abuse and time off work. Peveler et al.⁹ showed that lost productivity in women with endometriosis is equivalent to 11 working hours per woman weekly through absenteeism and presenteeism. Furthermore, studies revealed that women with CPP had fewer children likely due to poorer social adjustment and therefore often start their families later in life.⁹

Professor Abbott, Medical Director of Endometriosis Australia, revealed the yearly total economic burden of CPP in the reproductive aged population was A$9.5 billion in Australia.⁶ A survey of 407 women with either a confirmed diagnosis of endometriosis or CPP not related to endometriosis found women with endometriosis spent an average of A$3876 yearly on health costs, A$25,665 for productivity costs and A$1136 on carers. For those with CPP without a diagnosis of endometriosis, an average of A$4719 was spent on health costs, A$18,773 for productivity costs and A$1418 for carer costs.⁶ Most finances (75%–84%) were lost to productivity loss.⁶ Estimated outpatient visits cost for CPP for the US population of women aged 18–50 years is $881.5 million yearly.¹⁰ Prescription costs ranged from US $193 to US $2457 per woman yearly.¹¹

The aetiologies of CPP are diverse

The physiology of CPP can initially be classified as nociceptive and non-nociceptive. Nociceptive pain originates from the stimulation of pain-sensitive structures, which are affected in disorders of the musculoskeletal, urological, gynaecological and gastrointestinal systems.¹²

Musculoskeletal

Musculoskeletal disorders associated with CPP can involve the spinal, abdominal or pelvic complex of muscles. Noxious stimulation can induce peripheral afferents, primarily type c nerve fibres which can result in nociceptive pain.¹³ Pain may be localised to a specific trigger point or attributed to muscle hyperalgesia, as is evident in fibromyalgia.¹⁴ Muscle hyperalgesia can be explained by central sensitisation which increases signalling to the CNS and amplifies human’s perception of a peripheral stimulus.¹³ Inflammation of the ligaments, enthesitis and bursitis can also contribute to CPP.

Gynaecological

In gynaecological conditions such as endometriosis, the repeated inflammatory pain impulse from the affected organ, may induce cross-sensitisation whereby a false pain sensation from the organ supplied by the same dorsal root ganglion develops, contributing to CPP.¹⁵ Similarly, in painful bladder syndrome, the defect in the glycosaminoglycan layer of the bladder can result in continuous exposure of the bladder wall to potassium causing inflammatory cytokine and Toll-like receptor 4 release and resultant tissue irritation.¹⁶

Pelvic conditions that directly affect the nerves or pelvic nerve or plexus pathologies can also cause CPP. Common plexuses affected include the sacral plexus, inferior hypogastric plexus and branches of the lumbar plexus. Gynaecological procedures such as a hysterectomy or laparoscopic uterosacral nerve ablation can potentially damage the inferior hypogastric plexus resulting in visceral pelvic pain.⁶ Changes in pelvic vein circulation from pelvic interventions or thrombosis can result in pelvic varicose veins which increases the risk of vascular entrapment or sacral compartment syndrome.¹⁷ Nerve entrapment, leiomyomas, cauda equina syndrome and sacral cysts are associated with CPP.¹⁸

Psychosocial

Stress has also been shown to initiate and exacerbate visceral pain with patients with CPP having a higher incidence of anxiety, depression and sleep disorders. Repetitive emotional and physical trauma, in particular sexual abuse can exacerbate the somatic symptoms of CPP as well as contribute to the post-traumatic stress.¹⁹

Multiple patient factors may predispose to CPP

Risk factors for dysmenorrhea included younger age (<30 years), low BMI (<20), smoking, early menarche (<12 years), longer, irregular or heavy menstrual flow, clinically suspected pelvic inflammatory disease and history of sexual assault. Non-cyclical pelvic pain was associated with clinically suspected pelvic inflammatory disease, caesarean section scar, pelvic adhesions, previous miscarriage, sexual abuse and psychological morbidities including depression, hysteria and somatisation.²⁰ A strong inter-relationship between risk factors was also suggested with CPP rarely being caused by a single factor alone.²¹

As a significant proportion of the primary causes for CPP are gynaecological, an indirect correlation may exist between risk factors of common gynaecological conditions and CPP.²² Studies examining the incidence of surgically diagnosed endometriosis overall found that in comparison to Caucasian women, Black and Hispanic women had lower rates of disease while Asian women had similar rates of disease in comparison to Caucasian women.²³ While these studies should be interpreted cautiously due to risk of selection bias, race and ethnicity may indirectly have an association with CPP.

The standard terminology used in CPP is often inconsistent and poorly defined. The variation in the language is often dependent on the primary cause of the CPP and the affected body domain. Characteristics of CPP include persistent pain (>6 months), with the pain being localised to the pelvis, lower abdomen, low back, medial aspect of the thigh, inguinal region or perineum.²⁴ Language used to describe the pain experienced includes sharp, dull ache, burning, stabbing, electric shock-like sensation paraesthesia, pressure, heaviness or discomfort. Patients also report variations in the modality of the pain, describing it as persistent, continuous, recurrent, episodic and cyclical in nature.²⁵

An individual’s obstetric history can also contribute to CPP. A long-term follow up study, Bergström et al.²⁶ showed about 19% of women reported pelvic girdle pain to varying degrees 12 months post-partum. These results were similar to other follow-up studies 3-²⁷ and 6-years post-partum.²⁸

Several studies also suggest the mode of delivery may result in CPP. During a vaginal delivery, tearing of the levator ani muscle, perineum and neuromuscular injury may occur when a fetal head descends. Levator ani lacerations has been found to have an association with unexplained CPP. Results from a longitudinal study also showed an association between the use of forceps during at least one vaginal delivery and dyspareunia.²⁹

Caesarean section has also been shown to be a risk factor for CPP. About 12% of women continue to report pelvic pain 10.2 months after their caesarean delivery.³⁰ Possible causes for this pain includes iliohypogastric or ilioinguinal nerve entrapment, uterine scar defect and pelvic adhesions.³¹

Current variation in guidelines

There remains significant practice variation and a lack of clear guidelines surrounding the management of CPP. For many gynaecologists, surgical management with a laparoscopy is often considered the ultimate or definitive method for evaluating CPP and diagnostic laparoscopy is considered by many to be routine in the evaluation of chronic pelvic pain.³² However, many studies have demonstrated the major role of diagnostic laparoscopy only in the diagnosis of endometriosis or adhesive disease.³³

As there are several other causes of CPP, the resultant emphasis on laparoscopy can have a negative therapeutic effect on patients due to premature dismissal of the women’s pain.³⁴

For other gynaecologists, the adoption of a multidisciplinary team approach with the inclusion of physiotherapists and detailed exploration of other causes from the initial consult is their primary management, with laparoscopy only considered as a second-line investigative tool when the index of suspicion for endometriosis or adhesive disease requiring surgical intervention is high.^35,36 The range in current practice can potentially impact the continuity of care for patients and may result in negative long-term patient outcomes.

Endometriosis affects approximately 176 million women aged 15–49 years worldwide and is the leading gynaecological cause of CPP. This outnumbers the prevalence of breast cancer, prostate cancer and diabetes in the same demographics, and yet today a large gap exists between evidence and practice. The pelvic pain report also cited that The High Price of Pain November 2007 estimated that implementation of evidence-based treatments could halve the cost of chronic pain to the Australian economy. A systematic review of international guidelines for the management of CPP, Mardon et al.³⁷ demonstrated that on quality appraisal, guidelines on average, scored ‘excellent’ for the domains ‘scope and purpose’ (80.6%, SD = 13.3) and ‘clarity and presentation’ (74.4%, SD = 12.0); other domains, scored a ‘satisfactory’ or ‘poor’ result. NICE, RANZCOG and ESHRE for Endometriosis and Teede et al. (2018)³⁸, International Evidence Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome, Monash University, were the recommended guidelines for use.³⁷

Unfortunately, there is still a lack of high-quality research of the matter. In fact, according to Mardon et al.,³⁷ over 35% of guidelines for CPP management were not supported by evidence. Out of 15 pelvic pain guidelines, all recommended surgical or pharmaceutical interventions, 11 recommended psychological input and only 7 suggested physiotherapy.³⁷

No easy path exists for the management of CPP and the healthcare system has major improvements to make, concerning education, guidelines or government funding. However, these challenges are being acknowledged and ways to resolve them are gaining interest.

Analgesic options

CPP is complex to manage. Patients with CPP may experience significant pain in the perioperative setting. For example, in patients undergoing laparoscopic hysterectomy, preoperative pain is more predictive of postoperative pain than the presence of endometriosis.³⁹ This issue highlights the importance of optimising CPP prior to the perioperative period. Strategies to manage perioperative pain in patients with CPP may vary based upon CPP aetiology, individual comorbidities, nature of surgery and patient preferences.

Analgesic option based upon aetiology of pain

Overall, there is limited evidence regarding perioperative pharmacological analgesia in these conditions. However, for pain related to the reproductive system, studies support non-steroidal anti-inflammatory drugs (NSAIDs) as a first line analgesic for dysmenorrhoea in the community setting, which may help rationalise their use in the perioperative setting for patients with this issue.⁴⁰ For CPP related to the neurological system, neuropathic pain agents may be used.⁴¹ However, again, there is conflicting evidence regarding their use in CPP, with some larger trials failing to show benefit.⁴² There is conflicting evidence in this area particularly regarding endometriosis.⁴³ GnRH analogue, Linzagolix and hormonal therapy have been shown to significant reduce pelvic pain related to endometriosis.⁴⁴ Studies also suggest the role of vitamin D in the regulation of important cellular and signalling pathways involving gene expressions and cytokines in endometriosis. However evaluation of the efficacy of vitamin D in reducing the clinical symptoms achieved equivocal results, highlighting the need for further research.⁴⁵

Additionally, there is limited evidence regarding perioperative non-pharmacological management in patients with CPP. Psychological therapies as well as psychological management strategies of pain may have an important role.⁴⁶ Cognitive behavioural therapy has been well-studied in chronic pain, although less so in CPP.⁴⁷ In the perioperative setting, the role of both physical therapies and interventional strategies is limited due to logistical considerations.⁴⁸ In individuals who currently smoke, a positive correlation was observed between the cumulative pack-years of smoking and the severity of chronic pelvic pain.⁴⁹ Additionally, quitting smoking at least 3 weeks prior to surgery, resulted in improved post-operative pain outcomes compared to smoking cessation less than 3 weeks before surgery.⁵⁰

Analgesic option based upon comorbidities

Standard considerations apply to analgesic options in patients with CPP as in the general population with respect to comorbidities. Renal function, liver function and potential for medication interactions are considered in all populations, although patients with CPP may have specific comorbidities that influence these characteristics.

Renal dysfunction is seen in patients with CPP due to certain urological aetiologies. For example, patients with urinary retention may develop hydronephrosis with resultant renal dysfunction. Similarly, gynaecological malignancies may result in renal dysfunction, and their surgical management may predispose to acute kidney injury.⁵¹ Renal dysfunction is particularly relevant to the use of NSAIDs, which may be contraindicated in significant renal impairment.⁵² Opioid use may also be modified by renal dysfunction, depending on the presence or absence of renally-cleared active metabolites.⁵³

Hepatic dysfunction may occur with some causes of CPP. For example, in syndromes such as Fitz-Hugh Curtis, the causes of CPP (e.g. pelvic inflammatory disease) may occur with hepatitis and the subsequent risk of hepatic dysfunction.⁵⁴ Hepatic dysfunction may also occur with gynaecological malignancies with hepatobiliary metastases.⁵⁵ Hepatic endometriosis may also result in abnormal liver function.⁵⁶ In this setting, medications that lead to worsening of liver injuries, such as paracetamol, may need careful consideration. Hepatically-cleared medications such as NSAIDs and certain opioids may need dose reduction or avoidance.⁵⁷ When opioids are required for perioperative analgesia in the setting of hepatic dysfunction, fentanyl is relatively well-tolerated, although it will have a higher bioavailability due to its high hepatic extraction ratio.⁵⁸

Patients with CPP may already use medications that predispose them to medication interactions. For example, oxybutynin and solefenacin are commonly used to reduce urinary symptoms in patients with CPP. These medications, particularly when combined with opioids and antiemetics, may predispose to anticholinergic syndromes.⁵⁹ Similarly, amitriptyline and nortriptyline which may be used in conditions associated with CPP, may predispose individuals to serotonin syndrome (e.g. when used with tramadol).⁶⁰

Analgesic option based upon surgical procedure

The nature of the operation undertaken will affect decisions regarding perioperative analgesia, in particular local anaesthetic options and nerve blocks. Studies have shown that in pelvic floor operations, multimodal analgesia, including nerve blocks, can provide effective pain relief and minimise opioid use.⁶¹ Nerve blocks, in particular superior hypogastric plexus blocks, are shown to have potential benefit in CPP.⁶² However, they come with the associated risks of an additional procedure. Currently, there is insufficient evidence to suggest changing practice with respect to local anaesthetic management of perioperative pain based on a history of CPP.

Conclusions

While no clear standardised guidelines have been established for medical professionals in the routine management of CPP, strategies have been recommended to improve patient care and outcomes.

Firstly, given the vast array of potential causes of CPP, allowing additional time for proper exploration of the pain in the perioperative period can help better differentiate between gynaecological and non-gynaecological causes, allowing for more effective management.⁶³

Additionally, instead of a routine laparoscopy, the initial multidisciplinary team approach with the involvement of physiotherapists and conduction of provocation tests demonstrated better pain relief outcomes.⁶⁴

In the perioperative period, a transvaginal ultrasound has been shown to be useful in identifying soft markers of pathology which can help medical professionals determine whether laparoscopic surgery will be of benefit.⁶⁵ Finally, prior to surgery, patients should be thoroughly counselled on their expectations of the surgery. As 1/3 to 1/2of diagnostic laparoscopies yield negative results, the associated psychological devastation felt by patients may significantly impact their engagement with the medical process which is associated with poor pain outcomes.⁶⁶ For medical professionals who believe surgery will not be of significant benefit, microlaparoscopy or conscious pain mapping may be of more benefit.³⁴ The approach to the investigation and management of CPP is summarised in Figure 1.

Figure 1.

Approach to chronic pelvic pain.

Further research

There is significant scope for research in the perioperative management of CPP.

Recent advancements in MRI techniques and functional neuroimaging have unveiled intricate neural pathways and structural anomalies which contribute to pain perception. Additionally, genomic and proteomic studies have identified monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α as possible biomarkers for CPPS.⁶⁷ In perioperative patients with confounding symptoms, these biomarkers also have the potential to differentiate between CPPS and pain deriving from a different origin. Further mechanistic studies are required to fully understand the role of these biomarkers in the pathophysiology of CPPS.

Neuromodulation techniques, including transcutaneous electrical nerve stimulation, sacral neuromodulation, percutaneous tibial nerve stimulation and pudendal neuromodulation have shown promise in rewiring pain signalling and providing long-term relief.⁶⁸ However, more extensive multi-centre trials are required to confirm their efficacy in treating CPP.

Artificial intelligence has also emerged as a transformative paradigm in the management of CPP. AI techniques such as deep learning algorithms and machine learning have shown to be capable of identifying intricate patterns, correlations and predictive factors from data sets derived from genomics, proteomics, neuroimaging and clinical records. Additional, virtual pain assessment platformed, fuelled by AI, facilitate real-time monitoring of symptoms which can help in a clinician’s create personalised pain management strategies, ultimately improving peri-operative care.⁶⁹

Subsequently, further interventional studies are required. These studies may begin with the examination of pre-operative optimisation of CPP. In the perioperative period, in addition to individual drugs or devices, multi-modal analgesic strategies may also be examined. These studies will likely require a multidisciplinary approach and should assess for improvements in both short-term and long-term outcomes.

Finally, systematic appraisal of evidence is required. There is currently conflicting evidence regarding several core medications used in CPP management in the non-perioperative setting. Ongoing evaluation of evidence will be required to help bring evidence-based pain management strategies to the bedside for patients with CPP in the perioperative setting.

Footnotes

Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research,authorship,and/or publication of this article.

Funding

The author(s) received no financial support for the research,authorship,and/or publication of this article.

ORCID iD

Antoinette Lam

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