title: Lysophosphatidylcholine causes neuropathic pain via the increase of neuronal nitric oxide synthase in the dorsal root ganglion and cuneate nucleus.
abstract: In this study, we investigated the role of nitric oxide (NO) in lysophosphatidylcholine (LPC) induced peripheral neuropathy by the use of nitric oxide synthase (NOS) inhibitors and NO donor. We found that LPC treatment of the median nerve induced neuropathic pain behaviors (allodynia and hyperalgesia) and nerve demyelination. Immunohistochemistry revealed that the amounts of neuronal NOS-like immunoreative (nNOS-LI) neurons in both the dorsal root ganglion (DRG) and cuneate nucleus (CN) increased and peaked at 1 week after LPC treatment. Following electrical stimulation of the LPC-treated nerve, the number of c-Fos-LI neurons in the ipsilateral CN also increased in a dose-dependent manner following LPC injection and peaked at 1 week. Administration of L-NAME (Nω-Nitro-L-arginine methyl ester) or 7-NI (7-nitroindazole) 1 week after 4% LPC injection attenuated tactile allodynia and thermal hyperalgesia. However, the application of the NO donor S-Nitroso-N-acetylpenicillamine (SNAP) only exacerbated thermal hyperalgesia. After electrical stimulation of the LPC-treated median nerve, the number of c-Fos-LI neurons in the CN diminished in the L-NAME and 7-NI groups, but increased in the SNAP group. Taken together, our findings suggest that advanced NO made by the dramatically increased number of nNOS in the DRG and CN might be involved in the neuropathic sensation and boosted neuronal activity in the CN after LPC treatment.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Ying
authors.initials: HY
authors.lastname: Wang
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Tsai
authors.forename: Seu-Hwa
authors.initials: SH
authors.lastname: Chen
authors.forename: Chi-Te
authors.initials: CT
authors.lastname: Lin
authors.forename: June-Horng
authors.initials: JH
authors.lastname: Lue
mesh_terms: D000818:Animals; D004790:Enzyme Induction; D005727:Ganglia, Spinal / Q000201:enzymology*; D008244:Lysophosphatidylcholines / Q000633:toxicity*; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology*; D009437:Neuralgia / Q000139:chemically induced*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008244:Lysophosphatidylcholines; D052248:Nitric Oxide Synthase Type I