The proteome of acute muscle pain: Observations from acute hypertonic saline induced pain in humans

Despite widespread use of experimental acute pain models to mimic chronic pathologies, little exploration has been undertaken on the acute pain proteome in humans. We re-solved to explore molecular alterations evoked by acute bouts of hypertonic saline (HS) induced muscle pain and map the spread of evoked mechanical hyperalgesia. This study used a 2-cohort design in healthy human participants. Cohort one (n=16) underwent in-termittent blood sampling concurrent with intramuscular HS (5%) infusion to allow for the discovery of the proteomic and cytokine profile of acute muscle pain. Cohort two (n=10) underwent bilateral sensory testing during HS infusion, to map the spread of evoked mechanical hyperalgesia. Molecular analysis in cohort one revealed a diffuse ar-ray of proteins and cytokines showing altered expression in response to acute muscle pain. Particularly these alterations were linked to metabolism and immune response pathways suggestive of systemic effects of acute pain. Intriguingly, cohort two revealed a significant mechanical hyperalgesia which emerged in a diffuse pattern over the ipsilat-eral limb to HS-infusion. However, despite evidence of systemic molecular alterations, no such mechanical hypersensitivity was observed in the contralateral limb. This study demonstrates systemic molecular alterations resultant from acute bouts of HS-induced muscle pain with accompanying sensory interactions.