Plexin D1-IgG-mediated neuropathic pain

Abstract

Neuropathic pain (NP) is an intractable pain caused by a lesion or disease of the somatosensory nervous system. Some causes of NP are well-known, but in many cases it is difficult to identify the cause of NP. Therefore, it is challenging to treat it appropriately. Recently, autoantibody-mediated pain disorders have been recognized as novel NP causes in the field of autoimmune neurology. We recently discovered Plexin D1-IgG that binds to pain-conducting small dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons in patients with NP. Plexin D1-IgG bound to isolectin B4-positive unmyelinated C-fiber type small DRG and TG neurons and vasoactive intestinal peptide-positive postganglionic parasympathetic nerve fibers in the skin. NP patients with Plexin D1-IgG developed burning pain, tingling, and peripheral vascular dysfunction symptoms in their face, limb, and/or trunk. The coexisting disorders in patients with Plexin D1-IgG were allergic diseases, collagen diseases, and malignant neoplasms. Immunotherapies, including plasma exchange and intravenous methylprednisolone pulse therapy, are effective for NP in patients with Plexin D1-IgG, indicating Plexin D1-IgG might be pathogenic in NeP. In this review, we describe the concept of autoantibody-mediated NP and the clinical features of Plexin D1-IgG-mediated NP.