Lipid raft disruption as an opportunity for peripheral analgesia

Chronic pain conditions are unmet medical needs, since the available drugs, opioids, non-steroidal anti-inflammatory/analgesic drugs and adjuvant analgesics do not provide satisfactory therapeutic effect in a great proportion of patients. Therefore, there is an urgent need to find novel targets and novel therapeutic approaches that differ from classical pharmacological receptor antagonism. Most ion channels and receptors involved in pain sensation and processing such as Transient Receptor Potential ion channels, opioid receptors, P2X purinoreceptors and neurokinin 1 receptor are located in the lipid raft regions of the plasma membrane. Targeting the membrane lipid composition and structure by sphingolipid or cholesterol depletion might open future perspectives for the therapy of chronic inflammatory, neuropathic or cancer pain, most importantly acting at the periphery.