Minocycline inhibits somatic hyperalgesia induced by malocclusion through up-regulating spinal IL-10 expression in female rats.

Epidemiological studies have revealed that temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) often co-occur, significantly reducing patients' quality of life, with limited and unsatisfactory treatment options. This study aimed to investigate whether the microglial inhibitor minocycline attenuates unilateral anterior crossbite (UAC)-induced somatic hyperalgesia, examine its effects on inflammatory cytokine expression in the spinal cord, and explore the underlying mechanisms. In female rats, UAC significantly reduced mechanical withdrawal threshold and thermal withdrawal latency of hindpaws under corresponding stimulus conditions when compared to baseline. Somatic hyperalgesia was accompanied by significant up-regulation of ionized calcium-binding adapter molecule 1 (Iba-1, a microglial marker) and down-regulation of the mRNA of anti-inflammatory cytokine interleukin-10 (IL-10) in the L4-L5 spinal dorsal horn, while the protein expression of IL-10 was increased. Repeated intrathecal injection of minocycline for 5 days dose-dependently inhibited UAC-induced mechanical allodynia and thermal hyperalgesia in hindpaws, down-regulated Iba-1 expression, and up-regulated IL-10 expression in the spinal dorsal horn. Immunofluorescence analysis indicated that IL-10 primarily localized in microglia within the spinal dorsal horn. The analgesic effect of minocycline in UAC rats was blocked by intrathecal administration of IL-10 neutralizing antibody prior to minocycline injection. These findings indicate that minocycline attenuates UAC-induced somatic hyperalgesia by upregulating IL-10 expression and inhibiting microglial activation in the spinal cord. Therefore, minocycline may be a novel candidate analgesic for treating pain associated with TMD and FMS comorbidity.