Substance P spinal signaling induces glial activation and nociceptive sensitization after fracture.

Tibia fracture induces chronic activation of spinal microglia and astrocytes via Substance P release from C-fiber afferents, maintaining nociceptive sensitization. Inhibitors of glial activation or SP receptor antagonists partially reversed pain behaviors and glial activation.

The study used a rat tibia fracture model with casting, followed by behavioral pain assessments and pharmacological interventions targeting microglia, astrocytes, or SP receptors. Immunohistochemistry and PCR assessed glial activation. Additional experiments involved sciatic nerve C-fiber stimulation to mimic afferent SP release.

Understanding how Substance P and glial cells maintain chronic pain after fractures could lead to targeted therapies for CRPS and other chronic pain conditions involving neuroinflammation.

The study was conducted in rodents, which may not fully replicate human CRPS. The exact clinical relevance and long-term effects of glial inhibitors require further investigation.