Local passive heating does not increase histamine concentrations in skeletal muscle

During exercise, histamine concentrations increase in skeletal muscle. Previous small-scale investigations have indicated this is due, in part, to increases in intramuscular temperature above a suggested threshold of 38.4°C; however, it is unclear whether temperature alone is sufficient to trigger histamine release. The purpose of this investigation was to confirm that increases in muscle temperature, independent of exercise, are sufficient to induce histamine release in skeletal muscle and to investigate a potential temporal component of heat-induced histamine release. We hypothesized that elevated temperature would increase histamine concentrations in skeletal muscle and that a longer heating period would elicit greater increases in histamine. Eighteen participants (7M/11F, age 27±6 y, body mass index 23.7±1.6 kg/m 2 , mean±SD) underwent 60 minutes of local passive heating of the vastus lateralis via pulsed short-wave diathermy. A subset of these participants (n=8, 3M/5F, age 31±6 y, body mass index 24.8±1.2 kg/m 2 ) underwent an additional 40 minutes of heating (100 minutes total) to investigate the temporal effect of heating on histamine concentration. An intramuscular thermocouple (to measure temperature) and intramuscular microdialysis probes (to sample interstitial fluid) were placed in the heated area, directly beneath the diathermy unit. Interstitial fluid was analyzed for histamine concentrations by enzyme-linked immunosorbent assay, and local blood flow was estimated by ethanol washout. A one-way repeated-measures analysis of variance was used to investigate differences in muscle temperature, interstitial histamine concentrations, and local blood flow over time compared to baseline. Intramuscular temperature increased to 38.4°C by 40 minutes into heating (p< 0.01) and continued to increase to 38.9 [38.22, 39.51]°C (mean [95% CI]) at 60 minutes in all participants. In the subset, intramuscular temperature reached 39.0 [38.67, 39.38]°C at 100 minutes of heating. Histamine concentrations were 1.61 [1.15, 2.08] ng/ml at baseline and lower (1.19 [0.85, 1.57] ng/ml; p< 0.05) at 60 minutes of heating, but were not different in the subset at 100 minutes of heating (1.132 [0.49, 1.77] ng/ml; p=0.21). Local blood flow did not change during heating (p=0.39). We were unable to reproduce previous findings that local passive heating could increase histamine concentrations in skeletal muscle. The lack of a histamine response is corroborated by the evidence that local blood flow remained unchanged during heating. Further, there did not appear to be a temporal component (i.e., time above a certain temperature) that impacts histamine release. Thus, changes in temperature alone may be insufficient to evoke appreciable histamine release during exercise. Supported by NIH grant R01 AG072805, the Wu Tsai Human Performance Alliance andthe Joe and Clara Tsai Foundation, and the Eugene and Clarissa Evonuk Memorial Graduate Fellowship. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.