Complex regional pain syndrome (CRPS) is a condition of neuropathic pain, which is characterized by significant autonomic and inflammatory features. CRPS occurs in patients who have limb surgery, limb fractures, or trauma. Many patients may have pain resolve within twelve months of the inciting incident; however, a small subset progresses to the chronic form. This transitional process often happens by changing from warm CRPS with dominant inflammatory phase to cold CRPS, in which autonomic characteristics or manifestations dominate. Several peripheral and central mechanisms are involved, which might vary among individuals over a period of time. Other contributors include peripheral and central sensitization, autonomic alterations, inflammatory and immune changes, neurochemical changes, and psychological and genetic factors. Although effective management of the chronic CRPS form is often challenging, there are a few high quality randomized controlled trials that support the efficacy of the most commonly used therapeutic approaches.

The alpha-2 adrenergic receptor (α-2 AR) agonists have a long history of use in treating different clinical conditions, such as hypertension, psychiatric entities (e.g., attention-deficit hyperactivity disorder), chronic pain, panic disorders, and, lately, for treating opioid withdrawal syndrome. In recent years, α-2 AR medications have been administered as adjuncts for managing inflammatory conditions, depression, chronic pain, sleep and cognitive disorders. This review will provide some clinical applications in neuroscience for this class of drugs. Understanding the pharmacological mechanisms is essential to obtaining neurochemical data that demonstrate that α-2 AR agonists have potential clinical significance in neuroscience.