Highlights
- •PNT in pigs caused sensitivity to mechanical stimulation and mechanical allodynia.
- •PNT in pigs caused behavior changes but minor to non-existent motor dysfunction.
- •All behavior parameters were altered after treatment with gabapentin or morphine. Aprepitant failed to relieve any of the pain-related symptoms.
- •mRNA analysis of the site of injury indicates an inflammation phase followed by a neurogenic phase.
- •Spinal cord mRNA analysis shows an increase in a microglia marker and a later increase in BDNF.
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.
Key words
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Article info
Publication history
Published online: October 06, 2015
Accepted:
September 26,
2015
Received in revised form:
September 21,
2015
Received:
May 27,
2015
Footnotes
This study was funded by MD Biosciences and Lahav Research Institute. The authors have no conflict of interest to declare.
Identification
Copyright
© 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.
