Transgenic mice with a global depletion of toll-like receptor type 4 are largely protected from peripheral and central posttraumatic neuroinflammation.

Experimental bone fracture induces a posttraumatic inflammatory reaction which is characterized by local swelling, increased temperature, tenderness, thermal hypersensitivity and pain at the lesion site. As a consequence, some patients develop complex regional pain syndrome (CRPS), a chronic pain condition which often starts with exacerbating inflammation of the limb. The transmembrane receptor Toll-like receptor type 4 (TLR4) plays a central role in the innate immune response and not only engages with extracellular but also intracellular ligands, initiating intricate intracellular signaling cascades promoting inflammation.