Therapeutic targeting of the ceramide-to-sphingosine 1-phosphate pathway in pain

Approximately 20% of the population in Western countries suffers from chronic pain syndromes for which treatments are frequently insufficient or non-existent. In particular, chronic pain management with opiate/narcotic analgesics is often hampered by the development of analgesic tolerance and hyperalgesia, necessitating escalating doses to achieve pain relief. There is a major need for renewed focus on novel targets that will be effective in both neuropathic and inflammatory pain. Compelling evidence implicates ceramide-to-sphingosine 1-phosphate (S1P) pathways as contributors to pain of diverse etiologies. Moreover, S1P and its receptors are emerging as important neuronal and immune cell regulators interacting at several sites in the pain pathway. It is therefore timely and important to critically evaluate the pharmacological basis for targeting the ceramide-to-S1P pathway as an approach to pain management.