Acid-induced pain and its modulation in humans

Area of Science:

• Neuroscience
• Pain Research
• Molecular Biology

Background:

• The mechanisms underlying acid-induced pain are not fully understood.
• Proton-activated ion channels are known, but their role in pain signaling requires further investigation.

Purpose of the Study:

• To investigate the signaling pathways of acid-induced pain in human volunteers.
• To explore the involvement of specific ion channels and receptors in mediating acid pain.

Main Methods:

• Novel iontophoresis technique to deliver protons transdermally.
• Assessment of acid-induced pain in human volunteers under various conditions (e.g., capsaicin sensitization/desensitization, NSAID application, amiloride injection).
• Evaluation of temperature effects on acid-induced pain.

Main Results:

• Transdermal proton iontophoresis induced dose-dependent pain with rapid desensitization and slow recovery.
• Acid pain was augmented by capsaicin sensitization but not affected by desensitization, indicating involvement of both capsaicin-sensitive and insensitive neurons.
• Non-steroidal anti-inflammatory drugs (NSAIDs) significantly reduced acid pain but not heat pain, suggesting specific peripheral interactions.
• Amiloride inhibited acid-induced pain, supporting the role of acid-sensing ion channels (ASICs).
• Temperature had minimal effect on acid-induced pain.

Conclusions:

• Acid-sensing ion channels (ASICs) play a prominent role in mediating cutaneous acid-induced pain.
• Transient receptor potential vanilloid receptor-1 (TRPV1) has a minor role in acid pain.
• NSAIDs interact specifically with peripheral acid sensors.
• Both capsaicin-sensitive and insensitive sensory neurons contribute to acid pain.