Peripheral Nerve Transection Predominantly Drives Sympathetic Nerve Sprouting in Mouse Dorsal Root Ganglia

Area of Science:

• Neuroscience
• Pain Research
• Peripheral Nerve Injury Models

Background:

• Sympathetic sprouting in dorsal root ganglia (DRG) is linked to sympathetically maintained pain (SMP) after nerve injury.
• The specific factors driving sympathetic remodeling and SMP remain incompletely understood.

Purpose of the Study:

• To investigate whether nerve injury type (transection vs. crush) or site influences sympathetic remodeling and pain.
• To differentiate mechanisms underlying pain following different peripheral nerve injury models.

Main Methods:

• Comparison of L5 spinal nerve transection (SpNT) and partial sciatic nerve crush injury (PCI) models in mice.
• Utilized TH-IR immunostaining and Phox2b reporter mice to visualize sympathetic fibers.
• Assessed mechanical hypersensitivity and response to chemical sympathectomy.

Main Results:

• Spinal nerve transection (SpNT) induced significant sympathetic sprouting and elevated norepinephrine (NE) in DRG, causing mechanical hypersensitivity reversed by sympathectomy.
• Partial sciatic nerve crush injury (PCI) caused long-lasting mechanical hypersensitivity but no sympathetic sprouting or NE elevation, and was unaffected by sympathectomy.
• Sympathetic sprouting was more pronounced in transection injuries compared to crush injuries, irrespective of nerve site.

Conclusions:

• Nerve transection is a key factor driving sympathetic sprouting and sympathetically maintained pain (SMP).
• Crush-induced neuropathic pain likely involves distinct, non-sympathetic mechanisms.
• Distinguishing between injury types is crucial for accurate pain subtyping and targeted therapeutic strategies.