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

Abstract

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.

Sex-Dependent Glial Signaling in Pathological Pain: Distinct Roles of Spinal Microglia and Astrocytes

“…This may explain why an effect of minocycline was noted in phase I of the formalin-induced inflammatory pain model but no effect of CASP6 inhibition or Casp6knockout on phase I behavior was found. Interestingly, this effect of minocycline on phase I behavior was not found by two other groups who applied the drug via the systemic route in male mice and rats [62]. As we noted earlier, minocycline has many other mechanisms of action, including antimicrobial activity, strong metal chelation, and inhibition of matrix metalloprotease-9 [63].…”

Binge Ethanol Consumption Increases Inflammatory Pain Responses and Mechanical and Cold Sensitivity: Tigecycline Treatment Efficacy Shows Sex Differences

“…These drinking‐related changes in nociceptive sensitivity may be significant for binge drinkers and individuals with AUD. Given reports of pain reduction by minocycline (Bastos et al., ; Kapoor, ; Pu et al., ), and the results of our companion papers showing that tigecycline reduced binge and dependent EtOH consumption as well as withdrawal symptoms (Bergeson et al., ; Martinez et al., ; Syapin et al., ), we tested the hypothesis that tigecycline would alleviate several negative aspects of high EtOH consumption, while reducing drinking levels. A single medication that possesses the ability to treat several EtOH‐related phenotypes would represent a valuable AUD pharmacotherapeutic agent.…”

Qualitative sex differences in pain processing: emerging evidence of a biased literature

“…Further genetic and pharmacological experiments confirmed a requirement for TLR4 signalling in the mediation of neuropathic and inflammatory pain hypersensitivity in male but not female mice; the sex difference appeared to be confined to the spinal cord (also see ref. 133 ) and was related to testosterone levels. However, there was no evidence for differential Tlr4 expression levels in male and female mice 134 .…”