TLR4 and arthritic joint disease: Following tissue insult and nerve injury, TLRs (such as TLR2, TLR3, and TLR4) induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain (e.g. serum-transferred arthritis) and neuropathic pain [3,41,42].