New Drug Discoveries Aim to Help Veterans, Others With Chronic Pain

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Chronic pain is a serious problem in the United States and particularly so for veterans. At the 73rd Annual Scientific Convention of the Society of Biological Psychiatry meeting in New York City, May 10 to 12, Jennifer C. Naylor, PhD, presented results about a randomized control trial of 92 veterans with chronic low back pain treated with pregnenolone or placebo.

Naylor is a psychologist at the Durham VA Medical Center and noted in the beginning of her talk, called "Biomarker Candidates and New Therapeutic for PTSD, TBI and Pain—Accelerating for Bench to Bedside From Biomarker Candidates to a New Therapy for Pain," that the views expressed were her own and not those of the VA. She is also an associate professor in psychiatry and behavioral sciences at the Duke University School of Medicine.

Veterans have a higher rate of chronic pain than the civilian population, including back pain. According to one study, more than 65% of veterans reported pain in the past 3 months, and more female veterans than male veterans report chronic pain (75% to 50%).

Scientists are looking for new, non-opioid therapies to treat pain, she said, citing a recent study in JAMA that said opioids were no better than over-the-counter pain relievers for osteoarthritis, and amid concerns about unintentional overdoses at higher levels of opioids.

The need is urgent, as posttraumatic stress disorder, traumatic brain injury, and pain frequently co-occur in newly returning veterans from Iraq and Afghanistan, a combination of conditions recently described as a “polytrauma clinical triad.”

Pregnenolone is a neurosteroid, which are endogenous molecules enriched in the brain, she said. They are synthesized de novo from cholesterol and are produced in the adrenal glands, gonads, and other peripheral tissues.

They are neuroactive and and have pain-relieving properties. They are modulators of GABA_A receptors (proteins that were revealed as the potential target of a post-partum depression treatment a decade ago in experiments with mice) and NMDA receptors and others.

They have at least 7 properties relevant to pain relief, as they are potentially neuroprotective, anxiolytic, anticonvulsant, antidepressant, anti-inflammatory, anti-apoptotic (protecting the nerves), and have anti-aggression properties.

The study enrolled 41 veterans in a treatment group taking pregnenolone, and 41 in the placebo group. The primary endpoint was the mean weekly pain rating scales averaged from daily pain diaries. Neurosteroids and other small molecules were taken via blood samples.

The dosage of pregnenolone for those in the treatment group was 50 mg twice a day for 1 week, then 150 mg twice a day for 1 week, then 250 mg twice a day for 2 weeks.

The pregnenolone group did significantly better than the placebo group, with a 20% reduction in pain versus a 4% reduction in the placebo group. In addition, their low back pain ratings were inversely related with serum neurosteroid levels, suggesting that their lack of those neurosteroids could have been contributing to their pain.

Additionally, they had reduced levels of pain interfering in work and activity.