Roles of ASIC3, TRPV1, and NaV1.8 in the transition from acute to chronic pain in a mouse model of fibromyalgia.

Background: Tissue acidosis is effective in causing chronic muscle pain. However, how muscle nociceptors contribute to the transition from acute to chronic pain is largely unknown.

Results: Here we showed that a single intramuscular acid injection induced a priming effect on muscle nociceptors of mice.

Neurosensory mechanotransduction through acid-sensing ion channels.

Acid-sensing ion channels (ASICs) are voltage-insensitive cation channels responding to extracellular acidification. ASIC proteins have two transmembrane domains and a large extracellular domain. The molecular topology of ASICs is similar to that of the mechanosensory abnormality 4- or 10-proteins expressed in touch receptor neurons and involved in neurosensory mechanotransduction in nematodes.

Targeting ASIC3 for pain, anxiety, and insulin resistance.

The acid-sensing ion channel 3 (ASIC3) is a pH sensor that responds to mild extracellular acidification and is predominantly expressed in nociceptors. There is much interest in targeting ASIC3 to relieve pain associated with tissue acidosis, and selective drugs targeting ASIC3 have been used to relieve acid-evoked pain in animal models and human studies. There is accumulating evidence that ASIC3 is widely expressed in many neuronal and non-neuronal cells, such as neurons in the brain and adipose cells, albeit to a lesser extent than in nociceptors.