The HPA – Immune Axis in the Brain

The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain – free full-text /PMC3978367/ – Front Immunol. 2014;

In response to physiological and psychogenic stressors, the hypothalamic–pituitary–adrenal (HPA) axis orchestrates the systemic release of glucocorticoids (GCs).

By virtue of nearly ubiquitous expression of the GC receptor and the multifaceted metabolic, cardiovascular, cognitive, and immunologic functions of GCs, this system plays an essential role in the response to stress and restoration of an homeostatic state.

GCs act on almost all types of immune cells and were long recognized to perform salient immunosuppressive and anti-inflammatory functions through various genomic and non-genomic mechanisms.  

Self-administration of Hydrocortisone for Pain

General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity – free full-text /PMC6581742/ – J Inflamm Res. 2019;

Objective: To determine if patient self-administration of hydrocortisone will safely achieve superior symptom control for all hydrocortisone-responding disorders as it does for Addison’s disease and rheumatoid arthritis.

Methods: 2,480 participants with hydrocortisone-responding disorders were brought to a minimum symptom state using daily administered hydrocortisone tablets in a 24-week, open study.

Thereafter, participants used 5-day, low-dose hydrocortisone regimens to quench subsequent disorder exacerbations (flares) to maintain the minimum symptom state. Stressors such as emotional traumas, infections, allergies, and injuries were minimized to reduce disorder intensity, hydrocortisone consumption, and participant discomfort.  

The Critical Importance of Corticoid Hormones

e.hormone | The Hormones : Corticoids – Tulane University – 2007 or later

Here’s some basic information on corticoid steroids, like prednisone, which can often provide dramatic relief from inflammatory pain.

Unfortunately, these steroids act by suppressing our whole immune system, not just inflammation, so they become dangerous if taken too regularly for too long. For me, they can be the best pain relievers with the worst long-term consequences.

In my darker moments, I’m willing to make this pact with the devil: relieve my pain now and I’ll deal with the fallout later – especially since I don’t expect to have a particularly long life because my body is literally disintegrating due to the faulty collagen from EDS. 

Neuroinflammation and Cortisol Issues

Could Neuroinflammation Be Triggering the Cortisol Issues in ME/CFS and Fibromyalgia? – Health Rising – by Cort Johnson | Jun 18, 2020

More than any other substance, cortisol demonstrates how integral a role the stress response plays in the functioning of our body.

Our main stress hormone, cortisol is best known for the role it plays in jacking up our fight or flight system, but this versatile substance also

• affects our metabolism,
• tamps down inflammation,
• regulates blood pressure,
• affects glucose levels, and even
• impacts our sleep/wake cycle.

Modulation of pain by estrogens

Here are 4 PubMed scientific studies exploring how estrogen affects all different aspects of pain: its sensation, its interaction with opioid receptors, and its memory. Estrogen is clearly important, but the interactions with pain sensation are very complex.

Just like with hormone replacement therapy, the effects of estrogen on pain probably differ a great deal between individuals.

Pronociceptive and Antinociceptive Effects of Estradiol through Endogenous Opioid Neurotransmission in Women – NCBI – May 2006

Prominent interindividual and sex-dependent differences have been described in responses to sustained pain and other stressful stimuli. Variations in μ-opioid receptor-mediated endogenous opioid neurotransmission may underlie some of these processes.  

Neurosteroids for Anxiety Disorders

Neuroactive Steroid Levels in Patients With Generalized Anxiety Disorder – The Journal of Neuropsychiatry and Clinical Neurosciences – 2001

Anxiety isn’t just a state of mind, it’ s physical state of the body too.

Several neurotransmittersystems have been suspected to play a role in the pathophysiology of GAD [generalized anxiety disorder].  Various lines of research suggest dysregulation of the gamma-aminobutyric acid (GABA A )/ benzodiazepine (BZ) receptor complex.

These findings include decreased numbers and sensitivities of BZ receptors in patients with GAD and successful pharmacologic treatment of GAD with agents that target the GABA A / BZ receptor (e.g., benzodiazepines).  

Neurosteroid Hormone Therapy for Chronic Pain

Hormone Therapy for Chronic Pain: Are Neurosteroids the Answer? – By Forest Tennant, MD, DrPH, Ingrid Hollis, Lynn Kivell Ashcraft and Kris Walters – Oct 2019

What every person living with chronic pain should know about steroids, replenishment, and more.

While pain medication may provide you with you symptomatic, temporary relief so that you can function, hormone administration as part of a pain management plan can help to bring about the healing of damaged nerves and other tissues.

Supplementary Neurosteroid May Reduce Pain

Novel, ‘Non-Habit Forming’ Medication May Reduce Low Back Pain – Nancy A. Melville – Apr 2019  [It’s actually a supplement, not a “medication”.]

A novel, “non-habit-forming” neurosteroid appears to be effective and well tolerated in the treatment of chronic low back pain, new research suggests.

I’ve been exploring the benefits of supplementary neurosteroids for a while, but mainly as a remedy for my chronic anxiety. I’m thrilled to learn they could also ease pain a little.

In a double-blind, randomized controlled trial of almost 100 Iraq/Afghanistan-era veterans, those treated with a pharmaceutical-grade tablet formulation of pregnenolone showed “significant and meaningful reductions” in low back pain intensity ratings at 6 weeks compared with their peers who received matching placebo, investigators report.  

Neurosteroids: Endogenous Role in Human Brian

Neurosteroids: Endogenous Role in the Human Brian and Therapeutic Potentials – free full-text /PMC3139029/ – July 2011

This chapter provides an overview of neurosteroids, especially their impact on the brain, sex differences and therapeutic potentials.

Neurosteroids are synthesized within the brain and rapidly modulate neuronal excitability. Neurosteroids such as allopregnanolone are positive allosteric modulators of GABA-A receptors with powerful antiseizure activity in diverse animal models.

Neurosteroids increase both synaptic and tonic inhibition. They are endogenous regulators of seizure susceptibility, anxiety and stress.

This is exactly the kind of information I was looking for: a potential new treatment for the anxiety that has tormented me for decades. 

Benefits of GABA Supplementation

3 Amazing Benefits of GABA | Psychology Today – Michael J Breus Ph.D. – Posted Jan 03, 2019

GABA is both a chemical produced within the body and a supplement that’s made for ingestion.

Many medications interact with GABA and GABA receptors in the brain, altering their function to achieve certain effects, typically

• relaxation,
• pain relief,
• stress and anxiety reduction,
• lower blood pressure, and
• improved sleep.