Pain
-
Targeting the vascular endothelial growth factor A/neuropilin 1 axis for relief of neuropathic pain.
Vascular endothelial growth factor A (VEGF-A) is a pronociceptive factor that causes neuronal sensitization and pain. We reported that blocking the interaction between the membrane receptor neuropilin 1 (NRP1) and VEGF-A-blocked VEGF-A-mediated sensory neuron hyperexcitability and reduced mechanical hypersensitivity in a rodent chronic neuropathic pain model. These findings identified the NRP1-VEGF-A signaling axis for therapeutic targeting of chronic pain. ⋯ In rats with spared nerve injury-induced neuropathic pain, intrathecal administration of NRP1-4 significantly attenuated mechanical allodynia. Intravenous treatment with NRP1-4 reversed both mechanical allodynia and thermal hyperalgesia in rats with L5/L6 spinal nerve ligation-induced neuropathic pain. Collectively, our findings show that NRP1-4 is a first-in-class compound targeting the NRP1-VEGF-A signaling axis to control voltage-gated ion channel function, neuronal excitability, and synaptic activity that curb chronic pain.
-
Mirogabalin, a selective voltage-gated calcium channel α2δ ligand, improves peripheral neuropathic pain; however, its effects on patients with cancers including pancreatic ductal adenocarcinoma (PDAC) remain unknown. We analyzed the effects of mirogabalin on a KPPC ( LSL-KrasG12D/+; Trp53flox/flox; Pdx-1cre/+ ) mouse model of PDAC. Six-week-old KPPC mice received oral mirogabalin (10 mg/kg/day) (n = 10) or vehicle water (n = 14) until the humane end point. ⋯ Local myeloperoxidase + tumor-associated neutrophils and CD45R + B cells were unaltered. Mirogabalin enhanced the proliferative ability of PDAC cell lines with the upregulation of cyclins and cyclin-dependent kinases; however, it inhibited the potential of pancreatic stellate cells in vitro. Therefore, our results suggest that mirogabalin improves cancer-associated pain but enhances the proliferative potential of PDAC in vitro and in vivo.
-
Randomized Controlled Trial
Psychological and neurological predictors of acupuncture effect in chronic pain patients: a randomized controlled neuroimaging trial.
Chronic pain has been one of the leading causes of disability. Acupuncture is globally used in chronic pain management. However, the efficacy of acupuncture treatment varies across patients. ⋯ Furthermore, support vector machine models applied to the questionnaire and brain features could jointly predict acupuncture improvement with an accuracy of 81.48%. Besides, the correlations and models were not significant in the sham-acupuncture group. These results demonstrate the specific psychological, brain functional, and structural predictors of acupuncture improvement and may offer opportunities to aid clinical practices.