The injury-induced intense stimulation of spinal cord neurons causes lysophosphatidic acid (LPA) biosynthesis. LPA₁ receptor activation causes demyelination and sprouting of dorsal root fibers, leading to an induction of synaptic reorganization underlying allodynia, in which innocuous (tactile) stimuli cause intense pain. The LPA₁ signal also initiates the up-regulation of Ca_vα2δ1 in dorsal root ganglion and PKCγ in the dorsal horn, underlying mechanisms for characteristic neuropathic hyperalgesia in myelinated sensory (A-type) fibers. On the other hand, the LPA₃ receptor mediates microglia activation at the early stage after nerve injury and LPA-induced LPA biosynthesis. Thus, both the LPA₁ and LPA₃ receptors play key roles in the initiation step using a feed-forward system for neuropathic pain.