Substance-P-induced protein extravasation is bilaterally increased in complex regional pain syndrome

Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome

“…Previously we observed that an NK1 receptor antagonist partially reversed the development of hindpaw warmth, edema, spontaneous extravasation, and allodynia in the CRPS fracture model (Guo et al 2004). Furthermore, intravenous SP-evoked extravasation and edema responses are chronically enhanced after fracture in rats (Guo et al 2006) and SP-evoked extravasation responses in CRPS patients are also facilitated (Leis et al 2003). Collectively, these data suggest that SP-signaling is enhanced in the CRPS extremity.…”

Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I

“…We did not observe this. The facilitated effects of SP to promote extravasation in CRPS are likely due to post-junctional changes (Leis et al 2003) such as enhanced signaling through the SP NK1 receptors, or possibly by reduced activity of the SP degrading enzyme neutral endopeptidase (NEP) (Kingery et al 2001b;Leis et al 2003;Guo et al 2006). Thus the anti-NGF mediated reductions in fracture-enhanced SP levels may not be sufficient to reduce hind paw edema.…”

“…This model exhibits the classical signs of CRPS type I including allodynia, edema, warmth, and periarticular bone loss. There is also facilitated substance P (SP) signaling in the injured limb of this model (Guo et al 2004;Guo et al 2006) and in CRPS patients (Weber et al 2001;Leis et al 2003). Excessive SP signaling can directly induce keratinocyte nerve growth factor (NGF) expression and increase NGF levels in the skin of rodents (Amann et al 2000;Burbach et al 2001;Amann and Schuligoi 2004).…”

Role of NFκB in an Animal Model of Complex Regional Pain Syndrome–type I (CRPS-I)

“…9,26,48 Moreover, NFkB interacts with neuropeptides such as calcitonin gene related protein (CGRP) 35 and substance P (SP) 36 that have been found abnormally expressed during CRPS. 7,34 Finally, animal studies have revealed that NFkB is involved in spinal plasticity 39 and the development of neuropathic pain. 50,51 NFkB resides in the cytosol of many different cell types and can be activated by many triggers, including ultraviolet radiation, free radicals, cytokines, and products of bacterial and viral infections.…”