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Pain due to endometriosis. Are painkillers the solution?

Endometriosis is a gynecological health condition that affects 3-10% women who are in their reproductive-age. It is not a curable condition but can be successfully managed. Women suffering from Endometriosis suffer from a lot of pain. Often women have a lot of questions about how to deal with pain associated with endometriosis. One of the most frequently asked question is if painkillers are a solution to tackle with pain associated with endometriosis.

Pain and Endometriosis
Pain associated with endometriosis may feel like extremely painful period cramps. In many cases the pain might manifest as pelvic pain, lower back pain, pain in the legs, and pain during sexual intercourse, pain associated with bowel movement or severe rectal pain.

Endometriosis pain might be different for every person who experiences it. People often mistake it for regular period pain but there are a few ways to distinguish common period pain from endometriosis pain.

With Endometriosis pain,
1.The pain is severe and lasts for over 6 months. During this, women usually suffer from pain both prior to and during their menstrual period.
2.The pain is consistent and women who suffer from this type of pain usually are able to recognize and distinguish between the normal pain and endometriosis pain.
3.Other symptoms such as diarrhea, constipation, excessive bloating, nausea, severe headaches and difficulty focusing on day-to-day activities is also observed.
4.Women suffering from this kind of pain also suffer from depression in some cases.

Role of MMPs and inflammatory cytokines in endometriosis:
Endometriosis is accompanied by the upregulation of a family of downstream proteases, matrix metalloproteinases (MMPs) and bioactive signaling molecules, known as cytokines. It is now apparent that these molecules contribute to the development and progression of endometriosis.

Cytokines play a major role in the initiation, propagation, and regulation of the immune and inflammatory responses. They are produced by many cell types including endometriotic tissues and have a diverse role in the pathogenesis of endometriosis. Cytokines in the peritoneal fluid create an environment which induces the development and progression of endometriosis.

Several cytokines are found to be elevated in the peritoneal fluid of women with endometriosis.

The pro-inflammatory and pro-angiogenic cytokines are responsible for altered innervations and modulation of pain pathways in endometriosis patients. The release of these cytokines can worsen endometriosis-associated chronic pelvic pain.

Are painkillers the solution for endometriosis-associated pain?
For the treatment of endometriosis, painkillers are often the initial choice. Both the prescription and over the counter (OTC) pain relief medications are used for the treatment of endometriosis pain.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used painkillers. They are available both over the counter as well as on prescription. They work by blocking the development of prostaglandins, a type of biological compound responsible for pain.

For mild pain, simple analgesics such as paracetamol can be used. It is best to start NSAIDs the day before, or several days before period or pain is expected. This will give the medication time to block the development of prostaglandins in the body.

However, many women find that over-the-counter painkillers are not strong enough to treat the pain in moderate to severe endometriosis. The doctor then may then recommend to try different NSAIDs or a combination of NSAIDs or other therapies to get relief. One should always consult their doctor before administering any new medication.

This being said, long-term use of NSAIDs is often accompanied by a host of unwanted side-effects such as
1. Nausea
2. Vomiting
3. Diarrhea
4. Stomach upsets
5. Stomach ulcers.

Since NSAIDs have a number of side effects they are not meant for long-term use.

Highly Bioavailable Natural Supplements for Pain Reduction
A lot of focus is being given to nutraceuticals especially when it comes to the safe and efficient management of pain associated with endometriosis. Nutraceutical actives like curcumin, resveratrol, N-acetyl cysteine and Vitamin D have been confirmed as safe and effective through several clinical studies.

Curcumin
Various studies have reported the anti-inflammatory effects of Curcumin for the treatment of endometriosis.

Besides its anti-inflammatory property, curcumin also serves as an anti-endometriotic agent by modifying the MMP-9 activity. It inhibits both, the activity and expression of MMP-9. 

By decreasing the levels of MMP-9, it arrests the endometriotic cells proliferation. Curcumin shows beneficial effects in the treatment of endometriosis because of its antioxidant, anti-inflammatory and NF-kβ inhibition properties.

Curcumin inhibits the expression of NF-kappa-β, a master regulator of inflammation. Additionally, curcumin inhibits TNF-α-induced secretion of inflammatory cytokines, which has a role in the development of endometriosis. It also has an inhibitory effect on pro-inflammatory cytokines.

Most curcumin products in the market have very poor bioavailability. To address this issue, novel technology based products are being developed. Novel techniques such as UltraSol are being employed to improve the bioavailability of poorly soluble Curcumin. This bioavailable Curcumin obtained is several times more bioavailable compared to standard Curcumin.

Resveratrol
It is an aromatase inhibitor and works on the pain cycle to reduce pain.
Resveratrol is a natural phytoestrogen synthesized by plants, such as dark grapes and blueberries, after exposure to UV radiation.

It has several mechanisms of action with respect to endometriosis. Its anti-inflammatory effect is achieved through inhibition of cytokine, macrophages, and lymphocytes. It also affects cell proliferation and apoptosis by inhibiting the NF-kβ. Resveratrol works by suppressing the aromatase and COX-2 expression. 

By suppressing the expression of COX-2 and aromatase enzymes it helps in reducing the endometriosis-related pain.

The combination of curcumin and resveratrol has been found to have a synergistic anti-oxidant and anti-inflammatory effect. The effect is found to be highly effective in the successful management of endometriosis related pain.

N-acetylcysteine
NAC is a naturally occurring supplement that reduces the proliferative capabilities of endometrial cells through MMP-9 reduction. Proliferation can increase the risk of complication in pregnancy hence, the antiproliferative effect of NAC may help decreasing risk of infertility.

NAC acts by decreasing the cell proliferation and decrease in cell locomotory behavior, particularly relevant in endometriosis. In addition, NAC also downregulates inflammatory protein activity and gene expression. A study showcased NAC as a thiol-containing compound with active role in redox signaling, with effects that are far beyond a generic antioxidant capability.

NAC treatment induces a relevant reduction in endometriomas size, associated with decreased tissue inflammation and cell invasiveness.

Vitamin D
Vitamin D effectively controls endometriosis through cytokine production, which eventually decreases pro-inflammatory factors and increases anti-inflammatory factors.Studies have showcased significant reduction of dysmenorrhea pain with vitamin D supplements over the period of 2 menstrual cycles. This reduction in pain was due to decreased levels of pro-inflammatory cytokines and decreased the biological activity of prostaglandins.

DISCLAIMER: The information published above is for educational purposes only and should not be used in any other manner. The information is not intended to substitute medical/professional advice. The information should not be used to diagnose or treat a health problem or disease without consulting a qualified healthcare practitioner.

References:
https://www.dovepress.com/are-matrix-metalloproteinases-and-their-inhibitors-reliable-diagnosis–peer-reviewed-article-MNM

http://www.jmsr.eg.net/temp/JMedSciRes2159-4090204_112142.pdf

https://www.openaccessjournals.com/articles/role-of-immunologic-and-inflammatory-factors-in-the-development-of-endometriosis-indications-for-treatment-strategies.pdf

https://www.fertstert.org/article/S0015-0282(01)01816-7/pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680492/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651065/pdf/jocmr-05-153.pdf

https://www.endometriosis-uk.org/pain-relief-endometriosis#painkillers

https://www.healthline.com/health/endotough/pain-real-talk#2

https://www.preventmiscarriage.com/turmeric-spice-fights-endometriosis.html

https://pdfs.semanticscholar.org/b751/308895147cc8f48d8083aae25d6b9e8c88f2.pdf

https://medtube.net/tribune/resveratrol-overcomes-endometriosis-women-can-confirm/

http://www.clevelandclinic.org/reproductiveresearchcenter/docs/publications/515_Harlev_et_al_Targeting_oxidative_stress_to_treat_endometriosis.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662115/

https://www.ncbi.nlm.nih.gov/pubmed/22371927