Recent advances in understanding of various chronic pain mechanisms through lysophosphatidic acid (LPA) receptor signaling

Excerpt

Lysophosphatidic acid (LPA) receptor (LPA1) signaling plays the key role in initiation of nerve injury-induced neuropathic pain [1‐4]. LPA, which is produced in the spinal cord following the sciatic nerve injury causes a calpain-mediated demyelination of dorsal root fibers and sprouting through LPA1 receptor, leading to an induction of synaptic reorganization underlying allodynia. The LPA1 signaling also initiates the up-regulation of Ca_vα₂δ₁ in DRG, leading to an enhancement of spinal pain transmission underlying hyperalgesia. Similar LPA1-mediated chronic abnormal pain and underlying mechanisms are observed in mouse models with Meth-A sarcoma surrounding sciatic nerve (cancer model) or with chemotherapy (paclitaxel). Central neuropathic pain following spinal nerve injury is now recently found to include the LPA1-mediated mechanisms. In contrast, (arthritic) inflammatory pain following Complete Freund Adjuvant treatment fails to show the involvement of LPA1 signaling. Thus it seems that many models of neuropathic pain, but not inflammatory pain model include LPA1-mediated mechanisms. …