(274) Novel Neurosteroid Intervention for Chronic Low Back Pain in Iraq/Afghanistan-Era Veterans

Chronic low back pain symptoms are extremely common among Iraq/Afghanistan-era Veterans. However, pharmacological management for pain is frequently suboptimal, and many Veterans experience persistent and unalleviated pain symptoms and/or intolerable side effects to pain medications. Current medications such as opioids that are frequently used to treat chronic pain symptoms have side effect risks such as respiratory depression, addiction, sedation, and potentially lethal interactions with other drugs. There is thus an acute and immediate need for the development of effective, safe, and non-habit-forming pharmacological treatments for chronic pain disorders. Neurosteroids are endogenous molecules that are enriched in human brain and hold promise for pain therapeutics. Data in rodent models demonstrate that neurosteroids exhibit pronounced analgesic actions, and our data in Iraq/Afghanistan-era Veterans suggest that neurosteroids are decreased in the setting of pain symptoms in clinical populations. Neurosteroids are hence logical candidates for pain alleviation and have not been tested yet for this indication. We thus conducted a 6-week randomized, double-blind, placebo-controlled trial of pregnenolone versus placebo to determine if adjunctive pregnenolone has therapeutic utility for the treatment of chronic low back pain in Iraq/Afghanistan-era Veterans. The primary outcome measure was average pain intensity ratings from a daily pain diary. Secondary outcomes included pain interference scores. Pregnenolone was extremely well-tolerated. Veterans randomized to pregnenolone reported significant reductions in low back pain relative to those randomized to placebo (pain diary p=0.024; pain recall p=0.010). Pain interference scores for “work” (p=0.040) and “activity” (p=0.031) were also improved in Veterans randomized to pregnenolone compared to placebo. Pregnenolone may thus represent a new intervention for pain conditions that is safe, well-tolerated, non-habit-forming, and potentially efficacious for the alleviation of pain symptoms in Iraq/Afghanistan-era Veterans.