Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine
Author(s)
Boateng, EK
Novejarque, A
Pheby, T
Rice, ASC
Huang, W
Type
Journal Article
Abstract
Background
Heterogeneity is increasingly recognized in clinical presentation of neuropathic pain (NP), but less often recognized in animal models. Neurochemical dysregulation in rodent dorsal root ganglia (DRG) is associated with peripheral nerve trauma, but poorly studied in non‐traumatic NP conditions.
Methods
This study aimed to investigate the temporal expressions of activating transcription factor‐3 (ATF‐3), growth‐associated protein‐43 (GAP‐43), neuropeptide Y (NPY) and galanin in traumatic and non‐traumatic rat models of neuropathies associated with NP. Expressions of these markers were examined in the DRG at different time points following tibial nerve transection (TNT) injury and antiretroviral drug stavudine (d4T) administration using immunohistochemistry. The development of sensory gain following these insults was assessed by measuring limb withdrawal to a punctate mechanical stimulus.
Results
Both TNT‐injured and d4T‐treated rats developed hindpaw mechanical hypersensitivity. Robust expressions of ATF‐3, GAP‐43, NPY and galanin in both small‐ and large‐sized L5 DRG neurons were observed in the DRG from TNT‐injured rats. In contrast, d4T‐treated rats did not exhibit any significant neurochemical changes in the DRG.
Conclusions
Taken together, the results suggest that ATF‐3, GAP‐43, NPY and galanin are likely indicators of nerve trauma‐associated processes and not generic markers for NP. These experiments also demonstrate distinct expression patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug‐associated NP.
Heterogeneity is increasingly recognized in clinical presentation of neuropathic pain (NP), but less often recognized in animal models. Neurochemical dysregulation in rodent dorsal root ganglia (DRG) is associated with peripheral nerve trauma, but poorly studied in non‐traumatic NP conditions.
Methods
This study aimed to investigate the temporal expressions of activating transcription factor‐3 (ATF‐3), growth‐associated protein‐43 (GAP‐43), neuropeptide Y (NPY) and galanin in traumatic and non‐traumatic rat models of neuropathies associated with NP. Expressions of these markers were examined in the DRG at different time points following tibial nerve transection (TNT) injury and antiretroviral drug stavudine (d4T) administration using immunohistochemistry. The development of sensory gain following these insults was assessed by measuring limb withdrawal to a punctate mechanical stimulus.
Results
Both TNT‐injured and d4T‐treated rats developed hindpaw mechanical hypersensitivity. Robust expressions of ATF‐3, GAP‐43, NPY and galanin in both small‐ and large‐sized L5 DRG neurons were observed in the DRG from TNT‐injured rats. In contrast, d4T‐treated rats did not exhibit any significant neurochemical changes in the DRG.
Conclusions
Taken together, the results suggest that ATF‐3, GAP‐43, NPY and galanin are likely indicators of nerve trauma‐associated processes and not generic markers for NP. These experiments also demonstrate distinct expression patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug‐associated NP.
Date Issued
2015-02-01
Date Acceptance
2014-05-04
Citation
European Journal of Pain, 2015, 19 (2), pp.236-245
ISSN
1090-3801
Publisher
Wiley
Start Page
236
End Page
245
Journal / Book Title
European Journal of Pain
Volume
19
Issue
2
Copyright Statement
© 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC®.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor
Biotechnology and Biological Sciences Research Cou
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000348567300012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
BB/E52708X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Anesthesiology
Clinical Neurology
Neurosciences
Neurosciences & Neurology
PRIMARY SENSORY NEURONS
DIFFERENTIAL EXPRESSION
GAP-43 EXPRESSION
NEUROPEPTIDE-Y
PAIN
RAT
GALANIN
MODEL
INCREASES
CELLS
Publication Status
Published
Date Publish Online
2014-07-29