α2 Adrenoceptor: A Target for Neuropathic Pain Treatment

Neuropathic pain is originated from different alterations of the nervous system. The difficulty of treatment strongly impairs quality of life of affected people. It is associated with severe, chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli and pain perceived in response to normally non-noxious stimuli. The underlying mechanisms are complex and involve both peripheral and central nervous components. The noradrenergic system plays a pivotal role in the control of pain since its widespread distribution in the pain matrix representing a valuable therapeutic target. This review focused on the alpha(2) adrenoceptor subtype modulation as strategy for neuropathic pain relief. Drugs acting as direct alpha(2) adrenoceptor agonists (clonidine and dexmedetomidine) were analyzed as well as the indirect alpha(2) adrenoceptor modulators. The overview included norepinephrine reuptake inhibitors (reboxetine, maprotiline), serotonin/norepinephrine reuptake inhibitors (venlafaxine, milnacipran, amitriptyline, duloxetine, bicifadine) and the compounds characterized by a double pharmacodynamic mechanism combining the norepinephrine reuptake inhibition and the mu opioid agonist profile (tramadol and tapentadol). A summary of recent compounds was illustrated.