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Recently published research shows that acidosis-evoked discomfort—termed ‘sngception’—is a distinct somatosensory modality, offering new diagnostic targets.

One of the most mysterious somatosensory functions remains the perception of acidosis in muscle, according to a paper published in Science Advances. Muscle soreness has traditionally been lumped together with nociceptive pain, yet, according to the study authors, human and animal data demonstrate that acidosis-evoked discomfort—termed ‘sngception’—is a distinct somatosensory modality.

“To address the promiscuous nature of acid sensation, we have coined the term ‘sngception’ for this specific somatosensory function, to distinguish it from the nociceptor neuron-specific sensation of painful stimuli (nociception),” wrote corresponding study author Chih-Cheng Chen, PhD, of the Institute of Biomedical Sciences, and colleagues.

In the Taiwanese and Chinese languages, the word “sng” describes soreness or acid-like discomfort, the team explained.

“In the pain clinic, soreness (or sng) sensation is seen as a distinct and characteristic sensory phenotype of various acute and chronic pain syndromes (eg, delayed-onset muscle soreness or DOMS, fibromyalgia, and radicular pain),” the authors wrote. “It is also a sign of successful analgesia for acupuncture and many physical therapies.”

Proprioceptors, Not Nociceptors, Drive Acid-Induced Hyperalgesic Priming

The paper detailed evidence from both mouse and human studies suggesting proprioceptors play a role in sngception.

According to the authors, in two mouse models of chronic widespread pain, genetic deletion of the acid-sensing ion channel 3 (ASIC3) in group Ia proprioceptors—but not in Nav1.8-positive nociceptors—relieved acid-induced hyperalgesia and the priming that predisposes tissue to chronic pain.

“Chemo-optogenetically activating proprioceptors resulted in hyperalgesic priming that favored chronic pain induced by acidosis,” the researchers reported, adding that the likely mechanism involves an axon-reflex within the muscle spindle: local acidosis triggers glutamate release from proprioceptor terminals, amplifying crosstalk with nearby thin-fiber nociceptors and setting the stage for persistent hypersensitivity.

The research team reported that volunteers receiving intramuscular acidification reported an acid-like “sng” that was distinguishable from pain, and a 34-year-old male patient with spinal cord injury retained sng perception and joint position sense despite losing pain sensation.

Segregation of Sng & Pain

“We conclude that the sensation of muscle soreness is clearly segregated from nociception and other somatosensory sensations in this special case,” the authors wrote. “Thus, this nonpain soreness (sng) sensation could be detected by a spared subcategory of neurons. Alternatively, proprioceptors could be responsible for this somatosensory sensation of sng, a separate sensation.”

ASIC3 is currently implicated in osteoarthritis, rheumatic arthritis, and myofascial pain models, but its cell-specific contributions were unclear, the researchers stated. Muscle acidosis elicits a proprioceptor-based signal that underlies soreness and primes chronic pain, yet remains pharmacologically addressable, they noted, adding that exploiting this distinction could translate into more precise diagnostics and mechanistically targeted therapies.

“The segregation of sng and pain is a new concept in biology and requires further investigation in clinical and preclinical studies,” they wrote, suggesting future research include microneurography studies to verify whether human A-fiber proprioceptors fire in response to intramuscular acid.