title: Peripheral Neuritis Trauma in Pigs: A Neuropathic Pain Model.
abstract: The use of rodents in preclinical studies has contributed greatly to our understanding of the pathophysiology of chronic neuropathic pain. These animal models are limited because of their poor clinical translation. We developed a pig model for chronic pain caused by surgically induced peripheral neuritis trauma (PNT). Seventy-five percent of the animals exhibited mechanical and tactile allodynia, which are indicative of painful neuropathy, by day 28 after surgery. Importantly, the PNT-injured pigs retained their ability to walk or to stand on their injured leg. Messenger RNA analysis of acute inflammatory cytokines calcitonin gene-related peptide and brain-derived neurotrophic factor at the site of injury suggests transient inflammation followed by a persistent high level of neurologic markers. Gabapentin and morphine effectively inhibited hypersensitivity to von Frey filaments and to feather stimuli, and reversed spontaneous pain-related behavior in a dose-related manner. No analgesic effect was detected in PNT-injured pigs after treatment with aprepitant, similar to observations in humans and contrary to observations in rodents. In conclusion, PNT-induced trauma in pigs may comprise a valid preclinical model for the study of the chronification of peripheral nerve injury and for the study of new pain therapies.
  
  
  CONCLUSIONS
  This article presents the characterization of a new peripheral neuritis trauma (PNT) model in pigs. The pig PNT model could help close the translational gap between preclinical and clinical responses and may contribute to improved efficacy or safety of candidate drugs.
authors.affiliation: The Neufeld Cardiac Research Institute, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Castel
authors.affiliation: Lahav Research Institute, Kibutz Lahav, Negev, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Sabbag
authors.affiliation: Department of Veterinary Resources, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.affiliation: Neurology R&D Division, MD Biosciences, Nes-Ziona, Israel. Electronic address: sigal@mdbiosciences.com.
authors.forename: Sigal
authors.initials: S
authors.lastname: Meilin
mesh_terms: D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement; D010812:Physical Stimulation; D013552:Swine; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D000588:Amines; D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D015740:Calcitonin Gene-Related Peptide
keywords: CX3CR1; Sciatic nerve trauma; brain-derived neurotrophic factor; pain behavior; pain chronification