Format

Send to

Choose Destination
J Pain. 2016 Jan;17(1):36-49. doi: 10.1016/j.jpain.2015.09.011. Epub 2015 Oct 9.

Peripheral Neuritis Trauma in Pigs: A Neuropathic Pain Model.

Author information

1
The Neufeld Cardiac Research Institute, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
2
Lahav Research Institute, Kibutz Lahav, Negev, Israel.
3
Department of Veterinary Resources, The Weizmann Institute of Science, Rehovot, Israel.
4
Neurology R&D Division, MD Biosciences, Nes-Ziona, Israel. Electronic address: sigal@mdbiosciences.com.

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.

PERSPECTIVE:

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.

KEYWORDS:

CX3CR1; Sciatic nerve trauma; brain-derived neurotrophic factor; pain behavior; pain chronification

PMID:
26456763
DOI:
10.1016/j.jpain.2015.09.011
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center