A devastating health problem in the United States and abroad is the inadequate treatment of pain. One third of all Americans suffer from some form of chronic pain, and a third of these have pain, which is resistant to current medical therapy. The economic impact of pain is equally large at approximately $100 billion annually. Severe pain syndromes reduce quality of life in patients, partly because reduced analgesic effectiveness with chronic opiate therapy (i.e., hyperalgesia and tolerance) leads to escalating doses and distressing side effects. Accordingly, there is major interest in new approaches to maintain opiate efficacy during repetitive dosing for chronic pain, without engendering tolerance or unacceptable side-effects.
The invention relates to methods of treating pain using at least one of sphingosine kinase antagonist, S1P antagonist, or S1P receptor antagonist. The invention further relates to the use of S1P receptor agonists, such as Fingolimod, BAF312, Ponesimod, ONO-4641, CS-0777, KRP-203, PF-991, and W146, and antagonists, such as antibodies, in the treatment and prevention of neuropathic pain including cancer and chemotherapy-induced pain, acute and chronic inflammatory pain, and the development of opiate-induced hypersensitivity (hyperalgesia and allodynia), and antinociceptive tolerance. Kits comprising sphingosine kinase antagonists, S1P antagonists, S1P receptor agonists, and S1P receptor antagonists are also provided.