Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin

Area of Science:

• Neuroscience
• Pharmacology
• Physiology

Background:

• Substance P (SP) is a neuropeptide involved in pain and inflammation.
• Capsaicin is known to deplete SP from sensory neurons.

Purpose of the Study:

• To investigate the long-term effects of capsaicin pretreatment on substance P levels and neurogenic plasma extravasation in rats at different ages.
• To determine the role of substance P in neurogenic plasma extravasation.

Main Methods:

• Rats were pretreated with capsaicin at various ages (2, 10, or 20 days) or as adults.
• Immunoreactive substance P (I-SP) levels were measured in various tissues and neural structures.
• Neurogenic plasma extravasation was assessed.
• Substance P and other peptides were infused intra-arterially.

Main Results:

• Pretreatment in young rats (2 or 10 days) caused significant, long-lasting decreases in I-SP in the skin, peripheral nerves, and central nervous system, along with >80% inhibition of neurogenic plasma extravasation.
• Pretreatment in 20-day-old rats and adult rats resulted in reversible depletion of I-SP and reversible impairment of neurogenic plasma extravasation.
• Chronic denervation of the skin also decreased I-SP.
• Intra-arterial infusion of substance P induced plasma extravasation, while other tested peptides did not.

Conclusions:

• Capsaicin's action on substance P neurons is limited to primary sensory neurons.
• The results strongly suggest that the release of substance P is a key mediator of neurogenic plasma extravasation.