Inhibition of key neurotransmitter could reduce endometriosis-related pain

TRPV1 blockers could be a potential treatment option for endometriosis-associated pain.

Key Points

Headline:

• TRPV1 blockers could be a potential treatment option for endometriosis-associated pain.

Highlights:

• A group of researchers from Fudan University, Shanghai [link] has found a connection between endometriosis-related pain and elevated neurotransmitter (TRPV1) levels in the dorsal root ganglia of mice.
• The introduction of a TRPV1 antagonist (BCTC) led to a decrease in pain sensitivity, and also TRPV1 expression. Lowered TRPV1 levels also reduced the expression of the pro-inflammatory proteins such as calcitonin gene-related peptide (CGRP) and substance P (SP). These proteins are activated downstream in the TRPV1 signal transduction cascade.

What’s done here?

• 36 rats divided into a control group (n=9) and a model group (n=27).
• The model group rats underwent endometriosis-inducing surgery and again divided into three treatment subgroups. The ENDO group (no treatment), the BCTC group, and the vehicle group.
• Tail flick test to measure pain sensitivity were administered to the rats before and after surgery, and before and after treatments were given.
• The mice were then sacrificed, and their dorsal root ganglia were surgically removed, and TRPV1, CGRP and SP expression was measured using immunohistochemistry, Western blotting, and RT‑qPCR.

Key Results:

• Rats showed significantly less pain sensitivity after BCTC administration. No such significant differences in sensitivity found in the ENDO or vehicle group after treatment.
• BCTC treated rats displayed significantly less TRPV1, CGRP, and SP expression compared to the ENDO group.

Importance:

• Pain is the most common symptom of endometriosis. These results indicate that anti-TRPV1 therapies could help to alleviate pain related to endometriosis.

Limitations:

• This study only measured TRPV1, CGRP, and SP levels. It may be possible that a different protein, not measured in this study, is responsible for the observed changes in pain sensitivity.
• The changes in expression of the three proteins in this study could be correlated but not necessarily causing the perceived changes in sensitivity.

Lay Summary

This study published in the scientific journalMolecular MedicineReports[link] by Lian et al. from Shanghai, China, aims to explore the relationship between transient receptor potential vanilloid type 1 (TRPV1) and endometriosis-associated pain.

Pain is the most common symptom for women with endometriosis. TRPV1 is a protein found in the dorsal root ganglion area of the spinal cord. It plays a key role in activating pain sensitization pathways and pro-inflammation proteins like calcitonin gene-related peptide (CPRG) and substance P (SP). The dorsal root ganglion is the first station of the brain’s pain sensitization pathway, so it serves as an important area when studying pain transmission.

For this experiment, 36 rats were divided into a control group (n=9) and a model group (n=27). The model group rats underwent endometriosis-inducing surgery and were further subdivided into three treatment groups. The ENDO group (no treatment) the BCTC group, and the vehicle group (Cyclodextrin, the vehicle of BCTC). The pain sensitivity of the rats was measured using a tail flick test. The test was administered three times, before surgery to obtain a baseline reading, after surgery but before treatment with BCTC or cyclodextrin, and after treatment. The second and third tests were used to measure any difference in pain sensitivity caused by the treatments. TRPV1, SP, and CPRG levels dorsal root gangliaof the rats were also measured post mortem.

The results showed that the rats displayed significantly less pain sensitivity after treatment with BCTC compared to the ENDO group. Furthermore, the rats in the BCTC group had significantly lower TRPV1, SP, and CPRG levels than those in the untreated ENDO group.

These results indicate that TRPV1 expression is associated with a intensified sensitivity to pain. Therefore, blocking TRPV1 with the use of its antagonists can reduce pain sensitivity and potentially alleviate some of the suffering and discomfort associated with endometriosis.

These findings may provide a substantial basis regarding the neurological mechanisms behind the perception of endometriosis-related pain.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+28627595