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Updated: Dec 17, 2025

Establishing a Mouse Model of a Pure Small Fiber Neuropathy with the Ultrapotent Agonist of Transient Receptor Potential Vanilloid Type 1
Published on: February 13, 2018
Painful trigeminal neuropathy associated with anti-Plexin D1 antibody
Takayuki Fujii1, Ryo Yamasaki1, Yukino Miyachi1
1From the Department of Neurological Therapeutics (T.F., N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka; Department of Neurology (R.Y., Y.M., K.I., Y.H., T.M., J.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka; Translational Neuroscience Center (J.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Ookawa, Fukuoka; and Department of Neurology (J.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Chuou-ku, Japan.
Objective:
To determine whether anti-Plexin D1 antibody (Plexin D1-immunoglobulin G [IgG]), which is associated with limb and trunk neuropathic pain (NP) and binds to pain-conducting small unmyelinated dorsal root ganglion (DRG) neurons, exists in patients with idiopathic painful trigeminal neuropathy (IPTN) and whether Plexin D1-IgG binds to trigeminal ganglion (TG) neurons.
Methods:
We enrolled 21 consecutive patients with IPTN and 35 age- and sex-matched controls without NP (25 healthy persons and 10 with neurodegenerative diseases). We measured serum Plexin D1-IgG using a mouse DRG tissue-based indirect immunofluorescence assay (IFA) and by Western blotting (WB) using a recombinant human Plexin D1 (rhPlexin D1) accompanied by immunoadsorption tests with rhPlexin D1. The reactivity of Plexin D1-IgG toward mouse TG, brain, heart, and kidney was assessed by tissue-based IFAs.
Results:
Serum Plexin D1-IgG was detected more frequently in IPTN than in controls by both IFA and WB (14.3% vs 0%, p = 0.048). Three Plexin D1-IgG-positive patients also had limb or trunk NP and commonly showed tongue pain. In tissue-based IFAs, IgG from 2 Plexin D1-IgG-positive patients immunostained small TG neurons, which was prevented by preincubation with rhPlexin D1. Moreover, Plexin D1-IgG immunostaining mostly colocalized with isolectin B4-positive pain-conducting unmyelinated TG neurons. IFAs of other tissues with the same IgG revealed weak immunoreactivity only in endothelial cells, which was prevented by preincubation with rhPlexin D1.
Conclusions:
Plexin D1-IgG, which binds to pain-conducting small TG neurons in addition to DRG neurons, can be present in IPTN as well as limb and trunk NP.
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