Related Experiment Video
Updated: Jun 24, 2026
04:34
Modified Spared Nerve Injury Surgery Model of Neuropathic Pain in Mice
Published on: January 25, 2022
Peripheral Sympathetic Sprouting Drives Neuropathic Pain via Spinal Microglial P2Y12 Activation in a Rat Spinal Nerve
Tingting Yu1, Huan Huang1, Zhipeng Li2
1Department of Anesthesiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
Journal of Pain Research
|June 23, 2026
Summary
Peripheral sympathetic activity amplifies spinal neuroinflammation in neuropathic pain models. Targeting purinergic signaling may offer new pain relief strategies, but requires further clinical validation.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Sympathetically maintained pain (SMP) is complex, with sympathetic sprouting not always present.
- Peripheral sympathetic-sensory coupling may worsen spinal neuroinflammation in neuropathic pain.
- Investigating the link between peripheral sympathetic drive and spinal microglial P2Y12 signaling is crucial.
Purpose of the Study:
- To determine if peripheral sympathetic drive and spinal microglial P2Y12 signaling are parallel pathways or interconnected.
- To explore the peripheral-to-central axis in the rat spinal nerve ligation (SNL) model of neuropathic pain.
Main Methods:
- Rats underwent spinal nerve ligation (SNL) or sham surgery.
- Treatments included 6-hydroxydopamine (6-OHDA) to deplete sympathetic nerves and intrathecal ticagrelor to inhibit P2Y12 receptors.
- Assessed mechanical allodynia, microglial activation (Iba-1), P2Y12 expression, p38 MAPK phosphorylation, and spinal cytokines.
Main Results:
- SNL induced mechanical allodynia and increased spinal P2Y12, Iba-1, p38 MAPK phosphorylation, and pro-inflammatory cytokines.
- 6-OHDA treatment and intrathecal ticagrelor both significantly reduced allodynia and spinal neuroinflammation.
- Pharmacological occlusion showed no additive benefit of combined 6-OHDA and ticagrelor, suggesting a shared pathway.
Conclusions:
- Findings support a peripheral-to-central neuroimmune axis where sympathetic activity enhances spinal microglial P2Y12-p38 signaling in the SNL model.
- Purinergic signaling interfaces are potential therapeutic targets for SMP.
- Further clinical validation is needed for translating these findings to human patients.
