BDNF-VGF Pathway Aggravates Incision Induced Acute Postoperative Pain via Upregulating the Neuroinflammation in Dorsal Root Ganglia

Approximately one-third of postoperative patients are troubled by postoperative pain. Effective treatments are still lacking. The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF)-VGF (non-acronymic) in dorsal root ganglia (DRG) in postoperative pain. Pain behaviors were assessed through measurements of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Transcriptome analysis was conducted to identify potential targets associated with postoperative pain. Western blotting, immunofluorescence, and ELISA were employed to further detect macrophage activation as well as the expression of BDNF, VGF, TNF-α, IL-1β, and IL-6. Results showed that plantar incision induced both mechanical and thermal hyperalgesia. Transcriptome analysis suggested that plantar incision caused upregulation of BDNF and VGF. The expressions of BDNF and VGF were upregulated in isolectin B4-positive (IB4+) and calcitonin gene-related peptide-positive (CGRP+) neurons, rather than neurofilament 200-positive (NF200+) neurons. The activation of BDNF-VGF pathway upregulated expression of IL-6, TNF-α, and IL-1β and promoted the activation of macrophages. In conclusion, BDNF-VGF pathway aggravates acute postoperative pain by promoting macrophage activation and pro-inflammatory cytokine production, which may provide a new target for the treatment of postoperative pain.