Sex-independent suppression of experimental inflammatory pain by minocycline in two mouse strains

The research on sex differences in nociception and antinociception as well as sex and gender differences in pain and analgesia is a maturing field. There is a vast literature showing experimental and clinical pain suppressive effects induced by minocycline, especially in inflammatory pain. However, as far as we know, possible qualitative or quantitative sex differences in those effects remained to be examined. By employing the formalin test, which has two phases of experimental pain behavior that models nociceptive pain (i.e., first phase) and inflammatory pain (i.e., second phase), we initially evaluated the effect induced by minocycline in female or male C57BL/6 mice. The treatment reduced the second phase of licking behavior in both females and males, and the effects were quantitatively similar in both sexes. Likewise, the same sex-independent effect was observed in Swiss mice, suggesting a genotype-unspecific sex-independent effect. While minocycline is already being tested in clinical trials, this appears to be the first preclinical investigation of sex differences in the experimental pain suppressive effects induced by this widely studied drug. The independence of sex in the antinociceptive effect induced by minocycline may be hopefully translated to gender-independent analgesic effects, which would be surely promising in a therapeutic paradigm.