LUNA Explains: Pain In Endometriosis

Although there is a certain correlation between the symptoms described by patients and the location of lesions, there is often a discrepancy between the endometriosis lesions found through imaging and surgery and what patients actually experience.

This disease can be disabling and have a significant impact on quality of life.

The reasons for the pain are complex and remain poorly understood to this day.

Endometriosis-related pain is multi-factorial, i.e., several mechanisms are involved, particularly hypersensitivity phenomena.

Endometriosis lesions are the trigger for a chain of events which, via “domino effect”, leads to chronic pain.

Inflammation is the main mechanism responsible for pain during menstruation (dysmenorrhoea).

This pain during bleeding is often the first symptom reported by patients at an early stage of the disease.

In fact, it is bleeding from the endometriotic implants that triggers the inflammatory reaction.

For deeper lesions (damage to the vaginal and rectal walls), this bleeding leads to the appearance of microcysts.

When you take an anti-inflammatory drug (such as ketoprofen or ibuprofen), your menstrual pain is relieved, reduced or even disappears for several hours.

Long-term use of anti-inflammatory drugs is not recommended.

Adhesions are abnormal attachments between two tissue surfaces which lead to retraction of the surrounding tissue.

In the case of endometriosis, there are two sources of adhesions: inflammatory outbreaks in the implants and areas that have been operated on.

Adhesions cause pain because they limit freedom of movement of the pelvic organs, but also because they are themselves innervated (i.e., surrounded and connected to nerves).

The link between adhesions and chronic pelvic pain is a subject of debate in medical literature.

Treatment of adhesions may reduce chronic pelvic pain and dyspareunia in 46-87% of cases.

There is a connection between the location of the adhesion and the pain described by the patient.

Nerve infiltration

The repetition of inflammatory phenomena produces scar tissue which infiltrates the nerve structures.

When a nerve is irritated, it will automatically immobilise the tissues it affects (viscera, ligaments, tendons, muscles, etc.). The movement of the organs concerned becomes painful.

Neuro-angiogenesis (the word is more complicated, but you will understand quickly 😊)

Studies have highlighted neuro-angiogenesis phenomena, i.e., more simply an abnormal development of nerve endings from endometriosis implants, with a high density of small nerve fibres (the C fibres). These small nerve fibres are involved in the transmission of the pain message: they are involved in making you say “I hurt” in more common terms. 😊

The severity of pain is directly proportional to the density of these small nerve fibres: the more numerous they are, the stronger the pain you feel!

Neurogenic inflammation

Inflammation mediators activate the nerve endings.

The sensitised nerves will in turn produce inflammatory substances, which will sensitise the nerves again.

This vicious circle is known as peripheral hypersensitivity by neurogenic inflammation (i.e., the nerves themselves produce the inflammatory mediators).

Nerves are therefore responsible for pain in several ways: they are infiltrated by lesions; they develop new nerve endings and can produce inflammatory mediators leading to hypersensitivity of the peripheral nervous system.

The hypersensitivity of the peripheral nervous system leads over time to hypersensitivity of the central nervous system.

Chronic exposure to pain leads to central hypersensitivity, i.e., a chronic remodelling of the central nervous system that amplifies the feeling of pain. In other words, you become very sensitive to pain, you have difficulty with it, and it seems more and more intense as time goes by

The NMDA pathway, the “pain memory” pathway: NMDA receptors are usually closed channels that open under certain conditions such as intense pain experiences, chronic stress and prolonged morphine use.

Central hypersensitivity involves a decrease in the pain perception threshold and a diffusion of pain in time and space. It concerns the viscera but also the ligaments, tendons, muscles, bones and skin.

On clinical examination, there is hypersensitivity of the skin over the pelvis (allodynia) and of the muscles (pelvic myofascial syndrome).

Central hypersensitivity allows us to understand that pain can increase in intensity, frequency and location without the disease progressing, or that pain can be felt even if the initial cause has been treated.

In addition, a clinical score for pelvic hypersensitivity: PPSC (Pelvic Pain Sensitisation Score) has recently been developed.

In the pelvic region, there is an inter-organ awareness phenomenon, as if the organs talk to each other.

This is the concept of “pelvic-organ cross-talk”, in other words interference/intermodulation between the pelvic organs.

This could explain the frequent association of endometriosis with other dysfunctional conditions such as irritable bowel syndrome, painful bladder syndrome or vulvodynia.

Patients may in fact suffer from other chronic pelvic pain: fibromyalgia (associated with endometriosis in 30% of cases), gynaecological diseases (polycystic ovary syndrome PCOS, pelvic congestion syndrome, etc.), other pelviperineal conditions (pudendal or cluneal neuralgia, coccygodynia, sacroiliac pain).

Spinal pain can be transferred to the pelvic sphere. Maigne’s syndrome is responsible for projected pain, i.e., at a distance from the initial lesion. The pain is localised in the pelvis, but the origin of the pain is a dysfunction between the thoracic and lumbar vertebrae.

Finally, the importance of chronic post-operative pain (secondary to nerve damage and/or hypersensitivity mechanisms) should not be overlooked, especially neuropathic pain on your scars.

A single anatomical area, the pelvis, is painful but several organs and functions are affected, this is known as a complex pelvic pain syndrome.

Pain is obviously not “in your head”, but our brain plays a key role in analysing the pain message.

It can modulate the pain message. This faculty is used in the management of chronic pain through treatments such as cognitive-behavioural therapies, mindfulness meditation or hypnosis.

Our social and family environment and our cultural beliefs have an influence on our pain experience.

Anxiety, catastrophising, fear of having a serious illness, sleep disturbances and depression often accompany chronic pain. This is even more frequent in the case of endometriosis because of the delay in diagnosis (7 years on average) and the erratic medical treatment of patients.

We have seen that previous painful experiences activate the pain memory pathway. Women suffering from endometriosis have had at least one painful experience per month since their initial period.

The mechanisms of pain in endometriosis are multifactorial and still poorly explained.

Endometriosis lesions will cause a complex chain of events (involving inflammation, nerve infiltration, neurogenic inflammation, adhesions…) leading to peripheral and then central hypersensitivity.

Central hypersensitivity modifies our perception of the pain message in intensity and location.

Pain, a warning symptom, then becomes a disease in its own right.

The role of the algologist (pain doctor) is to analyse the different mechanisms involved, to “dismember” the pain and propose a treatment adapted to each mechanism.

Patient management is therefore multidisciplinary, individualised and adapted, considering the bio-psycho-social model of chronic pain.

Understanding the mechanisms of pain caused by endometriosis could enable early treatment to limit the phenomena of hypersensitivity and improve patient prognosis.