# PD-1/PD-L1 pathway relieves incision induced acute postoperative pain via inhibiting the neuroinflammation in dorsal root ganglion of rats

## TL;DR

This study shows that the PD-1/PD-L1 pathway can reduce acute postoperative pain in rats by reducing neuroinflammation in the dorsal root ganglion.

## Contribution

The novel finding is that PD-1/PD-L1 pathway activation alleviates incision-induced acute postoperative pain by inhibiting neuroinflammation.

## Key findings

- Inhibition of PD-1 expression worsened postoperative pain by increasing neuroinflammation.
- Upregulation of PD-1/PD-L1 reduced pain by suppressing neuroinflammation in dorsal root ganglion.
- PD-1/PD-L1 pathway activation is a potential therapeutic target for acute postoperative pain.

## Abstract

Acute postoperative pain represents a significant clinical challenge, yet its underlying mechanisms remain incompletely understood. A previous study found that PD-1/PD-L1can relieve chronic pain. Mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) were quantified in rats at baseline (pre-incision) and at postoperative timepoints of 2, 8, and 24 h. Concurrently, PD-1/PD-L1 expression levels and neuroinflammatory markers were assessed at the 24-hour terminal timepoint. PD-1 inhibitors and agonists were administered via intrathecal injection immediately after surgical incision and at 12 h postoperatively, respectively. It was found that incision surgery resulted in significant postoperative pain accompanied by upregulation of PD-1/PD-L1 and neuroinflammation. Inhibition of PD-1 expression could further exacerbate acute postoperative pain by upregulating neuroinflammation, whereas upregulation of PD-1 expression could alleviate acute postoperative pain by inhibiting neuroinflammation. Activation of the PD-1/PD-L1 pathway relieves acute postoperative pain induced by plantar incision. This may be a therapeutic target for acute postoperative pain.

The online version contains supplementary material available at 10.1038/s41598-025-31618-6.