In neuropathic pain the repeated minocycline treatment inhibited the mRNA and protein expression of the microglial markers and metalloproteinase-9 (MMP-9). The minocycline diminished the pronociceptive (IL-6, IL-18), but not antinociceptive (IL-1alpha, IL-4, IL-10) cytokines at the spinal cord level. In vitro primary cell culture studies have shown that MMP-9, TIMP-1, IL-1beta, IL-1alpha, IL-6, IL-10, and IL-18 are of microglial origin. Minocycline reduces the production of pronociceptive factors, resulting in a more potent antinociceptive effect. This change in the ratio between pro- and antinociceptive factors, in favour of the latter may be the mechanism of minocycline analgesia in neuropathy.
Rojewska, E., Popiolek-Barczyk, K., Jurga, A. M., Makuch, W., Przewlocka, B., & Mika, J. (2014). Involvement of pro- and antinociceptive factors in minocycline analgesia in rat neuropathic pain model. Journal of Neuroimmunology, 277(1–2), 57–66. https://doi.org/10.1016/j.jneuroim.2014.09.020