AbstractBackgroundNerve growth factor (NGF) is a neurotrophin that is increased in osteoarthritic joints of horses. In humans, NGF has been associated with pain, and both synovial and serum NGF concentrations are increased in osteoarthritic patients. Studies in humans also have shown that serum NGF concentration can increase with stress. Serum NGF concentration should be evaluated in horses with osteoarthritis‐associated lameness.ObjectivesQuantify and compare serum NGF concentration in horses with osteoarthritis‐associated lameness and sound horses. Additionally, the impact of short‐term stress on serum NGF concentration was investigated.AnimalsLame horses with radiographic evidence of osteoarthritis (n = 20), lame horses without radiographic changes in the affected joint (n = 20) and sound horses (n = 20). In addition, horses with acute fractures (n = 9) were sampled. To determine the effect of stress, serum from horses subjected to a stressful event (transportation, n = 5; stress confirmed by increased serum cortisol concentration) was analyzed.MethodsCross‐sectional clinical study (lame, sound, and fracture cohorts) and experimental longitudinal study (stress cohort). Serum NGF concentration was determined using a quantitative sandwich ELISA.ResultsSerum NGF concentration was increased in lame horses with radiographic evidence of osteoarthritis (P< .0001; median, 238 pg/mL; interquartile range [IQR], 63‐945 pg/mL) and in lame horses without radiographic evidence of osteoarthritis in the painful joint (P< .05; median, 31 pg/mL; IQR, 31‐95 pg/mL) compared with sound horses (median, 31 pg/mL; IQR, 31‐46 pg/mL). Serum NGF concentration did not increase with short‐term stress and was low in horses with fracture‐associated pain.Conclusions and Clinical ImportanceSerum NGF concentration was high in the cohort with advanced osteoarthritis and should be investigated as a marker for osteoarthritis‐associated pain.