Title:α<sub>2</sub> Adrenoceptor: a Target for Neuropathic Pain Treatment
VOLUME: 17 ISSUE: 2
Author(s):Lorenzo Di Cesare Mannelli, Laura Micheli, Letizia Crocetti, Maria Paola Giovannoni, Claudia Vergelli and Carla Ghelardini
Affiliation:Dept. of Neuroscience, Psychology, Drug Research and Child Health - Neurofarba - Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
Keywords:α2 adrenoceptor agonists, α2 adrenoceptor, neuropathic pain, norepinephrine reuptake inhibitors, norepinephrine,
serotonin/norepinephrine reuptake inhibitors, μ opioid agonist/norepinephrine reuptake inhibitors.
Abstract: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 α2 adrenoceptor subtype modulation as strategy
for neuropathic pain relief. Drugs acting as direct α2 adrenoceptor agonists (clonidine and
dexmedetomidine) were analyzed as well as the indirect α2 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 μ opioid agonist profile (tramadol and tapentadol). A summary of recent compounds
was illustrated.
