Potential of dehydroepiandrosterone in modulating osteoarthritis-related pain

Osteoarthritis (OA) is the most common form of degenerative arthropathy, and the primary symptom is chronic joint pain. Dehydroepiandrosterone (DHEA) exerts a chondroprotective effect against OA and has been reported to have potent structure-modifying effects on osteoarthritic cartilage, thereby attenuating disease progression. However, the ability of DHEA to modulate OA-related pain has not yet been verified. Recent evidence suggests that there may be a link between the pharmacological effects of DHEA and pain generation. For example, DHEA synthesized in the adrenal gland interferes directly with nerve growth factor (NGF) receptors, a major biochemical contributor to peripheral hypersensitivity. Similarly, endogenous DHEA produced in the spinal cord exerts a regulatory effect on nociception in neuropathic rats. In this short review, we discuss recent studies concerning crucial signalling cascades and molecular mechanisms involved in pain generation as well as the potential link between DHEA activity and nociception. Particular attention is given to the putative molecular mechanisms underlying the favourable efficacy of DHEA against pain generation. Elucidating the molecular mechanisms of DHEA against osteoarthritic pain may pave the way for the discovery and development of novel anti-OA drugs, as effective drugs for OA treatment are not currently available.