The complex role of serotonin and 5-HT receptors in chronic pain.

Serotonin [5-hydroxytryptamine (5-HT)] in the central nervous system and in the periphery has long been considered to have an important role in the control of pain, for example, through descending inhibition. In recent years, considerable research efforts have focused on the role played by 5-HT on acute or chronic pain states as well as on the identification of the respective 5-HT receptors involved. However, preclinical studies have reported conflicting observations, and numerous important questions remain unanswered. The purpose of this study is to provide an analysis of the recent developments in understanding the role of 5-HT both within the periphery and at the level of the spinal dorsal horn. We discuss the inhibitory or facilitatory influences exerted by 5-HT, through the descending 5-HT pathway, on spinal processing of nociceptive information in pathological pain states. Evidence with regard to the possible implication of the 5-HT(1A), 5-HT(2A), 5-HT(3), and 5-HT(7) receptors in pain modulation is also reviewed. Recent studies (both behavioral and clinical, relevant to these targets) have indeed demonstrated that 5-HT(1A) and 5-HT(7) receptor agonists or 5-HT(2A) and 5-HT(3) receptor antagonists may be promising therapeutic agents for the treatment of pain states.