Mol Pain
-
Randomized Controlled Trial
Human safety study of a selective neuronal adenylate cyclase 1 (AC1) inhibitor NB001 which relieves the neuropathic pain and blocks ACC in adult mice.
Calcium-dependent, neuronal adenylyl cyclase subtype 1 (AC1) is critical for cortical potentiation and chronic pain. NB001 is a first-in-class drug acting as a selective inhibitor against AC1. The present study delineated the pharmacokinetic (PK) properties of human-used NB001 (hNB001) formulated as immediate-release tablet. ⋯ Animal experiments further confirmed that hNB001 had strong analgesic effect in animal models of neuropathic pain. In brain slice prepared from the anterior cingulate cortex (ACC), bath application of hNB001 blocked the induction of long-term potentiation (LTP). These results from both rodents and human strongly suggest that hNB001 can be safely used for the future treatment of different types of chronic pain in human patients.
-
Neuropathic pain is a distressing medical condition with few effective treatments. The role of Vascular endothelial growth factor A (VEGFA) in inflammation pain has been confirmed in many researches. However, the mechanism of VEGFA affects neuropathic pain remains unclear. ⋯ However, these effects of sFlt1 can be blocked by rpVEGFA and by 740 Y-P. Therefore, our study indication that targeting VEGFA with sFlt1 reduces neuropathic pain development via the AKT/TRPV1 pathway in SNI-induced nerve injury. This study elucidates a new therapeutic target for neuropathic pain.
-
Abnormal pain has recently been estimated to affect ∼50 million adults each year within the United States. With many treatment options for abnormal pain, such as opioid analgesics, carrying numerous deleterious side effects, research into safer and more effective treatment options is crucial. To help elucidate the mechanisms controlling nociceptive sensitivity, the Drosophila melanogaster larval nociception model has been used to characterize well-conserved pathways through the use of genetic modification and/or injury to alter the sensitivity of experimental animals. ⋯ Underexpression of Armadillo resulted in hyposensitivity, while overexpression of wild-type Armadillo or expression of a degradation-resistant Armadillo resulted in hypersensitivity. Neither underexpression nor overexpression of Armadillo resulted in observed dendritic morphological changes that could contribute to behavioral phenotypes observed. These results showed that focused manipulation of Armadillo expression within the nociceptors is sufficient to modulate baseline response in the nociceptors to a noxious stimulus and that these changes are not shown to be associated with a morphogenetic effect.
-
Psoriasis is a common chronic skin inflammatory disease. Understanding the pathogenesis of psoriasis and identifying novel therapeutic targets are under investigation. ⋯ ARG1 and CXCL2 may serve as biomarkers and potential therapy for psoriasis. This may be related to the immune response and NLR pathway.
-
Trafficking and activation of N-methyl-D-aspartate (NMDA) receptors play an important role in initiating and maintaining postoperative remifentanil-induced hyperalgesia (RIH). Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome has been linked to the development of inflammatory and neuropathic pain. We hypothesized that activation of NLRP3 inflammasome mediates IL-1β release and contributes to RIH in rats by increasing NMDA receptor NR1 (NR1) subunit phosphorylation and decreasing glutamate transporter-1 (GLT-1) expression. ⋯ NLRP3 inflammasome activation mediates IL-1β release and contributes to RIH in rats by inducing NMDA receptor NR1 subunit phosphorylation and decreasing GLT-1 expression. Inhibiting the activation of the NLRP3 inflammasome may be an effective treatment for RIH.