Pregnenolone Decreases Veterans' Chronic Back Pain More than Placebo

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Nelson Vergel

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Use of pregnenolone resulted in a significant reduction in pain intensity rating in veterans with chronic low back pain after 4 weeks of treatment, findings of a recent randomized, double-blind, placebo-controlled clinical trial showed.

Jennifer Naylor, PhD, and a team of North Carolina-based colleagues aimed to learn whether adjunctive pregnenolone had a therapeutic for treatment of Iraq- and Afghanistan-era US military veterans with chronic low back pain. The findings suggested that the steroid hormone may be safe and effective for the treatment of such pain.

Naylor, from the Durham VA Health Care System, enrolled 94 veterans aged 18-65 years old with chronic low back pain who got treated at the Durham VA Health Care System over 6 weeks. To be eligible, the pain needed to exist most days for >6 months and a weekly mean intensity score of >4 at baseline. The pain needed to be restricted to thoracic vertebrae 6 or below or associated with radiation to the proximal part of the lower limb.


pregnenolone pain.jpg
 
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"Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment."


 
Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001.
Pain medicine (Malden, Mass.), 2010-10, Vol.11 (10), p.1469-1476
Subject


Objective.  Nearly half of Operation Enduring Freedom/Operation Iraqi Freedom veterans experience continued pain post‐deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self‐reported pain symptoms in humans. Design.  We determined serum neurosteroid levels by gas chromatography/mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self‐reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates. Setting.  Durham VA Medical Center. Results.  Allopregnanolone levels were inversely associated with low back pain (P = 0.044) and chest pain (P = 0.013), and DHEA levels were inversely associated with muscle soreness (P = 0.024). DHEAS levels were positively associated with chest pain (P = 0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (P = 0.002). Conclusions.  Neurosteroids may be relevant to the pathophysiology of self‐reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders.
 
Normalization of serum pregnenolone is associated
with enhanced pain control

F. Tennant; Veract Palliative Care Medical Clinic, West Covina, CA

Pregnenolone is the metabolic precursor of multiple adrenal and sex
hormones, and it also is a neurosteroid involved in regulating neuronal
plasticity and function. Consequently adequate body fluid concentrations
may be essential for long term pain control and neurologic function.
Subjects were (18) severe, persistent pain patients from a variety of
causes who had inadequate pain control with a morphine equivalency
of 50-100mg/d. They also had sub-normal serum pregnenolone concentrations
below 20ng/dl. Patients had their daily opioid dosage increased
to a morphine equivalence of 400-1000 mg/d. After 90 days a repeat
pregnenolone serum concentration was determined, and patients were
reassessed for pain score, sleep, endurance, and well-being. Six subjects
maintained at the higher morphine equivalence dosage decompensated
a few months into treatment and developed severe pain and a house or
bed-bound state. All demonstrated sub-normal serum pregnenolone
concentrations, so pregnenolone supplements ranging from 50 to 200
mg/d were administered. Serum pregnenolone concentrations raised to
normal in 14 of the 18 subjects and mean serum concentration raised
from 13.6 3.0 to 50.1 2.7 (P.001). All patients reported some
improvement in pain relief, endurance, sleep, and well-being. The six
decompensated patients restablished following pregnenolone administration
and a return to normal serum pregnenolone concentration. Considering
the essential importance of pregnenolone as a precursor hormone
and neurosteroid, pregnenolone should be studied as a biologic
marker for pain control and as a therapeutic adjunct.
(
 
Does pregnenolone decrease cortisol? I know there are many threads already discussing pregnenolone, but I've never read anything conclusive regarding it's effects on cortisol.
I've also read that high cortisol also causes back pain, which I have, and also suspect high cortisol.
 
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