Possible Therapeutic Options for Complex Regional Pain Syndrome

Abstract

Complex regional pain syndrome (CRPS) describes an array of painful conditions that are characterized by continuing regional pain. CRPS comprises severe and inappropriate pain in cases of complete recovery after trauma. Research on the pharmacological treatment of CRPS, however, has not been well investigated. In this study, we compared the pain relief effects of different drugs (URB597, pyrrolidine dithiocarbamate, and hydralazine) in a rat model of chronic post-ischemic pain-induced CRPS. After drug injection, CRPS-induced mechanical allodynia was significantly recovered. After three repetitive drug injections, mechanical sensitivity generally improved as hyper-nociception subsided. Reduced Nav1.7 expression at dorsal root ganglions (DRGs) was observed in the drug treatment groups. Neural imaging analysis revealed decreased neural activity for each drug treatment, compared to vehicle. In addition, treatments significantly reduced IL-1β, IL-6, and TNFα expression in DRGs. These results indicated that drugs could reduce the expression of inflammatory factors and alleviate the symptoms of chronic post-ischemic pain-induced CRPS.

The Effect of Super-Repressor IkB-Loaded Exosomes (Exo-srIκBs) in Chronic Post-Ischemia Pain (CPIP) Models

“…PDTC does not directly inhibit IκB phosphorylation, but rather inhibits the signaling required for IκB degradation via proteasome rats [ 4 , 8 ]. In addition, PDTC inhibits the oxidative stress in vivo and in vitro by increasing the antioxidant capacity.…”

“…In addition, PDTC inhibits the oxidative stress in vivo and in vitro by increasing the antioxidant capacity. Therefore, PDTC can contribute to the inhibition of NFκB activation through multiple mechanisms [ 4 ]. Moreover, SN50 blocks the nuclear import of NFκB and other transcription factors, such as activator protein 1, signal transducers and activator of transcription, and nuclear factor of activated T-cells [ 27 , 28 ].…”

“…Complex regional pain syndrome (CRPS) is a condition associated with neuropathic pain and is characterized by intractable pain, multiple system dysfunction, and motor and autonomic dysfunction [ 1 ]. CRPS can be classified into two subtypes based on the presence (type II) or absence (type I) of direct nerve injuries [ 2 , 3 , 4 ]. There are several medical treatments available for CRPS, such as prophylactic vitamin C, narcotics, anticonvulsants, such as gabapentin or pregabalin, tricyclic antidepressants, and ketamine.…”

“…However, in many cases these medications do not often have high efficacy. These therapeutic limitations are partly attributed to the insufficient evidence on the pathogenesis of CRPS [ 1 , 2 , 3 , 4 ].…”

“…The biological fluids in the blister and the spinal cord contain high levels of inflammatory mediators, including tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, which can activate or be induced by NFκB. Moreover, the abnormally expressed neuropeptides in CRPS, such as calcitonin gene-related protein and substance P, interact with NFκB [ 3 , 4 , 8 ].…”