How Neurosteroids Made Their Debut in Chronic Pain Care

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By Dr. Forest Tennant and Ingrid Hollis

In 1981, some neuroscience researchers discovered a group of hormones being made in the brain and spinal cord.  Some are also made in the gonads, the primary reproductive glands. 

Initially, the scientists didn’t know why the central nervous system (CNS) produces these hormones, but they soon learned that they protect, energize, and heal CNS tissues, such as nerves and glial cells that may be injured or damaged. They also found that these hormones control pain. 

The hormones were named neurosteroids because their chemical structure resembled that of the corticosteroids, such as prednisone and hydrocortisone.

A main function of neurosteroids is to heal injured nerve tissue and relieve pain. This includes the glial cells that cause neuroinflammation, central sensitivity, and constant pain. Neurosteroids are potent anti-neuroinflammatory hormones. 

The main neurosteroids are:

  • Pregnenolone

  • Allopregnanolone

  • Estradiol (estrogen)

  • Testosterone

  • Progesterone

  • Nandrolone

  • Dehydroepiandrosterone (DHEA)

You will note that some neurosteroids such as estrogen have biologic effects outside the spine, controlling mood, cognition and neurological health.

Neurosteroid Research

Animal research into neurosteroids is large, well done, and compelling, in that the studies clearly show that these hormones will benefit pain care. For example, rats that had their spinal cords damaged totally recovered when given neurosteroids. 

Glial cell inflammation -- which causes central pain -- was also controlled by neurosteroids, which are potent suppressors of neuroinflammation. Researchers found that if there was a tissue tear, injury or inflammation in the cells, neurosteroids immediately restored them to their normal state. 

Once the functions of neurosteroids were better understood, it was widely believed among neuroscientists that they could be a powerful therapeutic tool to treat severe chronic and intractable pain. 

Like many great scientific discoveries, the main clinical constituency didn’t know and didn’t care about these findings.  Fortunately, two clinical innovators figured out that neurosteroids can be utilized for treating two severe painful conditions: burning mouth syndrome and adhesive arachnoiditis (AA).  Treatment of the latter utilizes pregnenolone, DHEA, and palmitoylethanolamide (PEA).

The Transition from Animals to Humans 

The transition from giving a drug to laboratory animals to using them safely and effectively in humans takes a lot of time and experimentation.   Factors that have to be considered include dosage, formulation, and various combinations of neurosteroids. 

The first physician to make the transition is Dr. Susan Sklar, who has developed a neurosteroid protocol for the previously untreatable intractable pain condition known as burning mouth syndrome. 

Learning to great extent from Dr. Sklar’s success, I and my associates developed a neurosteroid protocol for adhesive arachnoiditis.  Results to date are gratifying and correlate with the therapeutic improvements seen in animal research.

In summary, neurosteroids are a group of hormones produced in the CNS that protect and heal nerve tissues.  Animal studies show they heal injured spinal cord nerves and glial cells, and suppress inflammation, regenerate tissues, and reduce pain.

Neurosteroids are not a substitute for pain treatment with opioids and neuropathic agents, but an additional resource that greatly enhances pain relief.  Experience to date should be a motivator to expand the use of neurosteroids for all intractable and chronic pain conditions.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. Readers interested in learning more about his research should visit the Tennant Foundation’s website, Arachnoiditis Hope. You can subscribe to its bulletins here.

Ingrid Hollis is a person in pain, patient advocate, and advisor to the Tennant Foundation.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.