Sterile water; a novel and promising human experimental muscle pain model
Abstract Background Intramuscular injection of hypertonic saline evokes pain with similar characteristics as clinical myalgia and is thus, considered a valid human experimental model. The aim of this study was to investigate if intramuscular injection of sterile water can be used as a human experimental pain model by comparing it with hypertonic and isotonic saline, and to analyze if the effects differ between men and women. Methods This randomized double blind and placebo-controlled study included 15 healthy women and 15 healthy age-matched men (mean (SD) age of 23.6 (2.4) years). The study comprised of three separate sessions, with at least one week of wash out between each session. Sterile water (i.e. the test-substance), hypertonic saline (active control), and isotonic saline (passive control) were injected intramuscularly into one of the masseter muscles in a randomized order. Pain intensity (VAS) was assessed every 15 th s after the injection and pain duration (s) as well as pain drawing area (au) were recorded. Pressure pain thresholds (kPa) were assessed every 5 min after injection during 30 min. Results All substances evoked pain ( P < 0001), but sterile water and hypertonic saline induced pain with higher intensity ( P < 0.001), longer duration ( P < 0.001), and larger pain drawing area ( P < 0.001) than isotonic saline. The pain intensity was higher for hypertonic saline than sterile water 45-165 s after injection ( P < 0.015), but there were no significant differences between them regarding maximum pain intensity, pain duration or pain drawing area. There was no significant difference in PPT values with time or between substances. The pain duration was longer in the men compared to the women for all substances ( P < 0.006), while the pain drawing area was larger in women after injection of hypertonic saline ( P < 0.003), but not after injection of the other substances. No other sex differences were found. Conclusion Injection of sterile water had similar effects as hypertonic saline on pain variables, but no effect on PPT. Hence, the model mimics clinical myalgia and may offer a novel and simpler alternative to hypertonic saline injections.