Gatekeeper for muscle cramps

After release from small-diameter, sensory neurons, the neuronal signaling molecule, or neuropeptide, called substance P (SP) transmits pain signals into the spinal cord by activating the neurokinin 1 (NK1) receptor. Beyond the transmission of pain signals, however, the exact role of SP in muscle pain was enigmatic. Now, research led by Chih-Cheng Chen of Academia Sinica, Taiwan, has shown that SP has analgesic effects in acid-induced muscular pain¹.

Chen and his colleagues repeatedly injected an acidic solution into the leg muscles of mice, causing increased pain sensitivity that lasted for more than two weeks. They repeated this in mutant mice lacking SP and found that the hypersensitivity was enhanced and lasted longer, suggesting that it is normally reversed by SP signaling.
When the researchers injected the mutants with acid and a substance that activates the NK1 signaling pathway, however, hypersensitivity returned to the same level as observed in normal mice.

Electrophysiological experiments revealed that SP inhibits acid-sensing proteins in the sensory neuron cell membrane and that this effect depends on the enzyme tyrosine kinase.

Surprisingly, the researchers also found that SP signaling alters the electrical properties of larger diameter sensory neurons with nerve endings in the muscles, by modulating the expression of specific types of potassium and sodium channels.