Endometriosis and the possible mechanisms of pain.

Chronic pain is associated with alterations in the structure and function of the brain.

Key Points

Importance:

• Understanding the mechanisms of pelvic pain associated with endometriosis is crucial for management and appropriate treatment.

Highlights:

• The inflammatory process is the starter of complex pain pathways through which pain signals are transmitted anteriorly from the dorsal horn of the spinal cord.
• While processing pain information, multiple brain regions interact with each other through several sophisticated mechanisms that are still not fully understood.

What's done here:

• This review discusses every possible mechanism of pain associated with endometriosis.
• The goal is to inspire the recognition of endometriosis-induced pain to help create individualized treatments for the future.

Remarks:

• The definition of the etiology and the complex pain process of endometriosis remains incomplete.
• At present, the mechanism underlying endometriosis-associated pain are inflammatory reactions, injury, aberrant blood vessels, and functional anomalies of the central or peripheral nervous system.
• Toxic chemicals released after inflammation are responsible for neuropathic pain by surrounding and affecting nociceptive receptors.
• This interaction transmitted from the afferent nerve to the posterior root of the spinal cord later reaches the specified cerebral cortex involved in nociception.
• Clinical studies have revealed that patients with endometriosis suffer from complex pain, of which neuropathic pain is a part. 
• Endometriosis-associated pain is linked to changes in brain structure and function, dysregulation of pain pathways, and increased activity in brain regions that result in hyperalgesia.

Lay Summary

The most common clinical symptoms of endometriosis are chronic pelvic pain and infertility. It is often not enough to treat pain symptoms with hormonal therapy or a surgical approach. Moreover, the stage of endometriosis has weakly associated with the amount, size, location, and degree of pelvic pain. 

In this review, Fan et al. from the Department of Obstetrics and Gynecology of Tongi Medical College, Huazhong University, Wuhan, China, explained the possible pathways of pain in endometriosis with literature-based evidence.

Based on our knowledge, chronic pelvic pain can be divided into 3 main categories; nociceptive, neuroceptive, and nociplastic pain.

Deep infiltrating endometriosis shows high nerve density and several nerve growth factors and receptors such as NGF and NGFRp75. Studies have shown higher rates of dysmenorrhea, dyspareunia, and chronic pelvic discomfort in patients with perineural invasion that may be related to the abovementioned high nerve density.

The nerve endings are influenced by the physical and chemical factors surrounding the endometriotic lesion. These signals are transferred to the spinal cord and then to the relevant parts of the brain.

Another cause of peripheral pain in endometriosis may be angiogenesis which produces large numbers of cells, chemokines, and toxic substances around nociceptive receptors that can cause neuropathic pain.  

In addition to the abovementioned mechanisms, the authors also evaluate the dysfunction of congenital or adaptive immune cells, the negative effects of increased estrogens,  and anatomic distortions caused by the lesions to describe the complex pain map of endometriosis. Furthermore, they focused on the structural and functional changes observed during the perception of chronic pain in the brain which is the cause of hyperalgesia. The authors expressed their hope about the wide utility of the multiparameter single-cell technique and future breakthroughs in neuroimaging for a better understanding of the endometriosis pain mechanism. 

This educational review has recently been published in the journal named "Expert Reviews in Molecular Medicine".

Research Source: https://pubmed.ncbi.nlm.nih.gov/36059111/