Involvement of pro- and antinociceptive factors in minocycline analgesia in rat neuropathic pain model

•Activation of pro- and antinociceptive factors is observed.•Minocycline inhibits upregulation of IL-6, -18, and MMP-9 mRNA in spinal cord.•Minocycline inhibits upregulation of IL-6, -18, -10, MMP-2, -9, and TIMP-1 mRNA in DRG.•Minocycline and MMP-9 Inh.I exert better analgesic effects than does SB203580.•Minocycline restores the equilibrium between the pro- and antinociceptive factors.

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.

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