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.