CRPS typically develops after an injury, surgery, heart attack, or stroke. Investigators estimate that 2–5% of those with peripheral nerve injury, and 13-70% of those with hemiplegia (paralysis of one side of the body) will develop CRPS. In addition, some studies have indicated that cigarette smoking was strikingly present in patients and is statistically linked to RSD. This may be involved in its pathology by enhancing sympathetic activity, vasoconstriction, or by some other unknown neurotransmitter-related mechanism. This hypothesis was based on a retrospective analysis of 53 patients with RSD, which showed that 68% of patients and only 37% of controls were smokers. The results are preliminary and are limited by their retrospective nature. 7% of people who have CRPS in one limb later develop it in another limb. Pathophysiology
Inflammation and alteration of pain perception in the central nervous system are proposed to play important roles. The persistent pain and the perception of nonpainful stimuli as painful are thought to be caused by inflammatory molecules (IL-1, IL2, TNF-alpha) and neuropeptides (substance P) released from peripheral nerves. This release may be caused by inappropriate cross-talk between sensory and motor fibers at the affected site. CRPS is not a psychological illness, yet pain can cause psychological problems, such as anxiety and depression.
Intramuscular botulinum injections may benefit people with symptoms localized to one extremity. Ketamine
Ketamine, a dissociative anesthetic, appears promising as a treatment for CRPS. It may be used in low doses if other treatments have not worked. No benefit on either function or depression, however, has been seen. Bisphosphonate treatment
As of 2013, high-quality evidence supports the use of bisphosphonates (either orally or via IV infusion) in the treatment of CRPS. Bisphosphonates inhibit osteoclasts which are cells involved in the resorption of bone. Bone remodeling, via osteoclast activity in resorption of bone, is thought to sometimes be hyperactive in CRPS. It is hypothesized that bone resorption causes acidification of the intercellular milieu and this activates nerves involved in nociception that densely innervate bone causing pain; therefore inhibiting bone resorption and remodeling is thought to help with regards to pain in CRPS. CRPS involving high levels of bone resorption, as seen on bone scan, is more likely to respond to bisphosphonate therapy. Opioids
Opioids such as oxycodone, morphine, hydrocodone, and fentanyl have a controversial place in treatment of CRPS. These drugs must be prescribed and monitored under close supervision of a physician, as these drugs will lead to physical dependence and can lead to addiction. Thus far, no long-term studies of oral opioid use in treating neuropathic pain, including CRPS, have been performed. The consensus among experts is that opioids should not be a first line therapy and should only be considered after all other modalities (non-opioid medications, physical therapy, and procedures) have been trialed.