Testosterone, DHEA, and Pain

Optimizing hormonal levels can help pain in many ways. Correcting thyroid deficiency, despite normal blood tests, can markedly decrease pain. This is also the case for low adrenal function when adrenal support with the prescription cortef, or natural support (e.g. an herbal supplement that supports adrenal function) is given. Research by Professor Hillary White showed that prescribing natural testosterone to women who have Fibromyalgia can decrease pain. Now a recent animal study suggests that both testosterone and DHEA, another adrenal hormone that is converted to testosterone, may decrease neuropathic pain when taken on a regular basis. One caution though. DHEA could briefly increase pain for the first several hours before blocking it long term (see below). In general, it is a good idea to keep hormone levels, including DHEA and Testosterone, optimized in patients with Fibromyalgia and other chronic pain conditions.

As an aside, it's interesting that the study concludes that this information could be used to develop new (read "expensive and patentable") DRUGS instead of simply saying that optimizing DHEA and Testosterone levels may help. Of course, there's not much money to be made that way…

Published as doi: 10.1096/fj.07-8930com.
(The FASEB Journal. 2008;22:93-104.) 2008;22:93-104.
© 2008

Biochemical and Functional Evidence for the Control of Pain Mechanisms by Dehydroepiandrosterone Endogenously Synthesized in the Spinal Cord

Equipe Stéroïdes et Système Nociceptif, Institut des Neurosciences Cellulaires et Intégratives, Unité Mixte de Recherche 7168/LC2-Centre National de la Recherche Scientifique, Université Louis Pasteur, Département Nociception et Douleur, Strasbourg Cedex, France² Correspondence: Equipe Stéroïdes et Système Nociceptif, Institut des Neurosciences Cellulaires et Intégratives, Unité Mixte de Recherche 7168/LC2-Centre National de la Recherche Scientifique, Université Louis Pasteur, Département Nociception et Douleur, 21 rue René Descartes, 67084 Strasbourg Cedex, France.

We investigated the role and mechanism of action of dehydroepiandrosterone (DHEA) produced by the spinal cord (SC) in pain modulation in sciatic-neuropathic and control rats. Real-time polymerase chain reaction (PCR) after reverse transcription revealed cytochrome P450c17 (DHEA-synthesizing enzyme) gene repression in neuropathic rat SC. A combination of pulse-chase experiments, high performance liquid chromatography (HPLC), and flow-scintillation detection showed decreased DHEA biosynthesis from pregnenolone in neuropathic SC slices. Radioimmunoassays demonstrated endogenous DHEA level drop in neuropathic SC. Behavioral analysis showed a rapid pronociceptive and a delayed antinociceptive action of acute DHEA therapy. Inhibition of DHEA biosynthesis in the SC by intrathecally administered ketoconazole (P450c17 inhibitor) induced analgesia in neuropathic rats. BD1047 (sigma-1 receptor antagonist) blocked the transient pronociceptive effect evoked by acute DHEA administration. Chronic DHEA therapy increased and maintained elevated the basal nociceptive thresholds in neuropathic and control rats, suggesting that androgenic metabolites generated from daily administered DHEA exerted analgesic effects while DHEA itself (before being metabolized) induced a rapid pronociceptive action. Indeed, intrathecal administration of testosterone, an androgen deriving from DHEA, caused analgesia in neuropathic rats. Together, these molecular, biochemical, and functional results demonstrate that DHEA synthesized in the SC controls pain mechanisms. Possibilities are opened for pain modulation by drugs regulating P450c17 in nerve cells.