title: Novel expression pattern of neuropeptide Y immunoreactivity in the peripheral nervous system in a rat model of neuropathic pain.
abstract: BACKGROUND
  Neuropeptide Y (NPY) has been implicated in the modulation of pain. Under normal conditions, NPY is found in interneurons in the dorsal horn of the spinal cord and in sympathetic postganglionic neurons but is absent from the cell bodies of sensory neurons. Following peripheral nerve injury NPY is dramatically upregulated in the sensory ganglia. How NPY expression is altered in the peripheral nervous system, distal to a site of nerve lesion, remains unknown. To address this question, NPY expression was investigated using immunohistochemistry at the level of the trigeminal ganglion, the mental nerve and in the skin of the lower lip in relation to markers of sensory and sympathetic fibers in a rat model of trigeminal neuropathic pain.
  
  
  RESULTS
  At 2 and 6 weeks after chronic constriction injury (CCI) of the mental nerve, de novo expression of NPY was seen in the trigeminal ganglia, in axons in the mental nerve, and in fibers in the upper dermis of the skin. In lesioned animals, NPY immunoreactivity was expressed primarily by large diameter mental nerve sensory neurons retrogradely labelled with Fluorogold. Many axons transported this de novo NPY to the periphery as NPY-immunoreactive (IR) fibers were seen in the mental nerve both proximal and distal to the CCI. Some of these NPY-IR axons co-expressed Neurofilament 200 (NF200), a marker for myelinated sensory fibers, and occasionally colocalization was seen in their terminals in the skin. Peptidergic and non-peptidergic C fibers expressing calcitonin gene-related peptide (CGRP) or binding isolectin B4 (IB4), respectively, never expressed NPY. CCI caused a significant de novo sprouting of sympathetic fibers into the upper dermis of the skin, and most, but not all of these fibers, expressed NPY.
  
  
  CONCLUSIONS
  This is the first study to provide a comprehensive description of changes in NPY expression in the periphery after nerve injury. Novel expression of NPY in the skin comes mostly from sprouted sympathetic fibers. This information is fundamental in order to understand where endogenous NPY is expressed, and how it might be acting to modulate pain in the periphery.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Room 1215, Montreal, Quebec, H3G 1Y6, Canada. claire.magnussen@mail.mcgill.ca.|Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, H3A 0G1, Canada. claire.magnussen@mail.mcgill.ca.
authors.forename: Claire
authors.initials: C
authors.lastname: Magnussen
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Room 1215, Montreal, Quebec, H3G 1Y6, Canada. shih-ping.hung@mail.mcgill.ca.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Hung
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, McIntyre Medical Building, 3655 Promenade Sir William Osler, Room 1215, Montreal, Quebec, H3G 1Y6, Canada. alfredo.ribeirodasilva@mcgill.ca.|Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, H3A 0G1, Canada. alfredo.ribeirodasilva@mcgill.ca.|Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A 0C7, Canada. alfredo.ribeirodasilva@mcgill.ca.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-da-Silva
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D009437:Neuralgia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000293:injuries / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation
chemical_list: D009478:Neuropeptide Y; D015740:Calcitonin Gene-Related Peptide