untonuggan: A hand drawn spinning wheel covered in roses (spinning wheel briar rose)
[personal profile] untonuggan
From Liisa Hantsoo and C. Neill Epperson. Premenstrual Dysphoric Disorder: Epidemiology and Treatment. Curr Psychiatry Rep. 2015 Nov; 17(11): 87.

Progesterone levels are low during menses and the follicular phase and are mirrored by progesterone's main metabolite, allopregnanolone (ALLO), also a neuroactive steroid. Progesterone and ALLO increase in the luteal phase and decrease quickly around menses. This chronic exposure followed by rapid withdrawal from ovarian hormones may be a key factor in the etiology of PMDD [12]. In a recently developed animal model of PMDD based on progesterone withdrawal, rats in withdrawal from physiological doses of progesterone exhibited social withdrawal and anhedonia, symptoms characteristic of PMDD [13]. Indeed, preclinical research demonstrates that chronic progesterone exposure followed by rapid withdrawal is associated with increased anxiety behavior and alterations in γ-aminobutyric acid (GABA)A receptor function [12–14]. Recent work suggests that this effect may not be due to progesterone itself, but progesterone's main metabolite ALLO, as blocking progesterone conversion to ALLO blocks the aforementioned effects of progesterone [15].

ALLO is a potent positive allosteric modulator of the GABAA receptor, similar to alcohol or benzodiazepines, with anxiolytic, anesthetic, and sedative properties [16••]. It is possible that women with PMDD have developed tolerance to the arousal-reducing and GABA-enhancing effects of ALLO.

...

What is that you say about GABA?

From Pain: Hope through Research

GABA (or gamma-aminobutyric acid) is predominately an inhibitory neurotransmitter in that it generally decreases or blocks the activity of neurons. Most of what we know of its role in pain is related to its function in inhibiting spinal cord neurons from transmitting pain signals and therefore dampening pain. Chemicals that are similar to GABA have been explored as possible analgesics, but because GABA is so widespread in the nervous system it is difficult to make a GABA-like drug without affecting other nervous system functions. As we learn more about the specific roles of GABA receptors, drug development may be accelerated.

INTERESTING.

If I had all the monies I would fund a study about the link between GABA, chronic pain, and PMDD like...10 years ago. BUT ANYWAY I leave these thoughts for you my darlings, in the hopes that it may help someone.

Meanwhile a bit of my brain is still going "so, PMDD is possibly my brain suffering monthly withdrawal from its own chemicals. GREAT."

Date: 2016-10-12 03:53 pm (UTC)
lilysea: Books (Books)
From: [personal profile] lilysea
Thank you for posting about this sort of stuff. ^_^

Date: 2016-10-13 03:11 am (UTC)
lilacsigil: 12 Apostles rocks, text "Rock On" (12 Apostles)
From: [personal profile] lilacsigil
Ooh, very interesting! My PMDD was definitely worse in my late 20s than it is now, but it's still not good. The anxiety component of it is the only part getting worse - the pain is greatly improved, migraines only 50% of cycles, depression not as crashingly bad.

I wonder if women with PMDD have lower/no response to GABA analog medication?

Date: 2016-10-13 05:47 pm (UTC)
shanaqui: Harriet Vane from the Lord Peter Wimsey mysteries, smiling, text: imagine ((Harriet) Imagine)
From: [personal profile] shanaqui
*learning about GABA in "the science of the mind" right now*

*ponders*

If I go the neurology route, I shall attempt to investigate!

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