A role for proprioceptors in sngception

Area of Science:

• Neuroscience
• Sensory Physiology
• Pain Research

Background:

• Proprioceptors are mechanosensory neurons crucial for monitoring muscle status and body position.
• While typically non-nociceptive, proprioceptors express the pro-nociceptive acid-sensing ion channel 3 (ASIC3).
• The role of proprioceptors in acidosis sensing (sngception) remains largely unexplored.

Purpose of the Study:

• To investigate the function of proprioceptors in sensing acidosis.
• To determine if ASIC3 in proprioceptors contributes to acid-induced pain.

Main Methods:

• Genetic deletion of ASIC3 in proprioceptors versus nociceptors in mice.
• Chemo-optogenetic activation of proprioceptors.
• Intramuscular acidification in human subjects and a spinal cord-injured patient.

Main Results:

• Genetic deletion of ASIC3 specifically in proprioceptors abolished acid-induced chronic hyperalgesia in mice.
• Proprioceptor activation promoted hyperalgesic priming, favoring acidosis-induced chronic pain.
• In humans, acidification induced acid perception but not pain; however, a spinal cord-injured patient retained proprioception and sngception.

Conclusions:

• Proprioceptors, through ASIC3, play a significant role in sensing acidosis (sngception).
• These findings suggest a novel function for proprioceptors beyond mechanosensation, extending into chemosensation.
• Evidence from both murine models and human studies supports the involvement of proprioceptors in sngception, potentially mediated via the spinal dorsal column.