Sterile water; a novel and promising human experimental craniofacial muscle pain model

Background: The aim of this study was to investigate if intramuscular injection of sterile water can be used as a human experimental pain model that resembles clinical craniofacial muscle pain and to analyse if the effects differ between sexes.

Methods: This randomised, double-blind, placebo-controlled cross-over study included 30 healthy age-matched women and men (23.6 ± 2.4 years). At three sessions, with at least one week of washout in between, 0.2 mL of either sterile water (test-substance), hypertonic saline (58.5 mg/mL; active control) or isotonic saline (0.9 mg/mL; passive control) was randomly injected into the right masseter muscle. Pain intensity (VAS) was continuously assessed during 5 min whereafter pain duration (s) and pain area (au) were calculated; pressure pain thresholds (PPT;kPa) were recorded every 5 minutes during 30 minutes.

Results: Sterile water evoked pain of similar intensity (74.5 ± 49.9) as hypertonic saline (74.0 ± 50.5); whereas, isotonic saline evoked low-intensity pain (11.4 ± 23.4). The pain induced by sterile water and hypertonic saline had higher intensity (P < 0.001), longer duration (P < 0.001) and larger pain area (P < 0.001) than isotonic saline. There were no significant differences in any pain variable between sterile water and hypertonic saline. The PPT did not change significantly after any substance, except for in women 5 minutes after sterile water injection (P < 0.002). Pain duration was longer in the men for all substances (P < 0.006), while the pain area was larger in women after injection of hypertonic saline (P < 0.003).

Conclusion: These results indicate that pain evoked by sterile water resembles clinical muscle pain and may offer a novel and simpler alternative to hypertonic saline injections.