Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine

E K Boateng; A Novejarque; T Pheby; A S C Rice; W Huang

doi:10.1002/ejp.541

Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine

E K Boateng, A Novejarque, T Pheby, A S C Rice, W Huang

Medical Sciences

Imperial College London

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

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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 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 expressionsmall- 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 patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug-associated NP.

Original language	English
Pages (from-to)	236-245
Number of pages	10
Journal	European Journal of Pain
Volume	19
Issue number	2
Early online date	28 Jul 2014
DOIs	https://doi.org/10.1002/ejp.541
Publication status	Published - Feb 2015

Bibliographical note

© 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Funding sources

E.K.B. was funded by a BBSRC PhD studentship. A.N., A.S.C.R. and T.P. were funded by a Wellcome Trust Strategic Award (London Pain Consortium; ref. 083259). A.S.C.R. and W.H. were funded by the Innovative Medicines Initiative Joint Undertaking (Europain; grant agreement no. 115007). We thank Pfizer for providing stavudine.

Conflicts of interest

None declared.

Funded by
BBSRC PhD studentship
Wellcome Trust Strategic Award. Grant Number: 083259
Innovative Medicines Initiative Joint Undertaking. Grant Number: 115007

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Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/
Final published version, 543 KBLicence: CC BY

Wenlong Huang
Person: Academic

Cite this

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title = "Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine",

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 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 expressionsmall- 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 patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug-associated NP.",

author = "Boateng, {E K} and A Novejarque and T Pheby and Rice, {A S C} and W Huang",

note = "{\textcopyright} 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC{\textregistered}. Funding sources E.K.B. was funded by a BBSRC PhD studentship. A.N., A.S.C.R. and T.P. were funded by a Wellcome Trust Strategic Award (London Pain Consortium; ref. 083259). A.S.C.R. and W.H. were funded by the Innovative Medicines Initiative Joint Undertaking (Europain; grant agreement no. 115007). We thank Pfizer for providing stavudine. Conflicts of interest None declared. Funded by BBSRC PhD studentship Wellcome Trust Strategic Award. Grant Number: 083259 Innovative Medicines Initiative Joint Undertaking. Grant Number: 115007",

year = "2015",

month = feb,

doi = "10.1002/ejp.541",

language = "English",

volume = "19",

pages = "236--245",

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T1 - Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine

AU - Boateng, E K

AU - Novejarque, A

AU - Pheby, T

AU - Rice, A S C

AU - Huang, W

N1 - © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®. Funding sources E.K.B. was funded by a BBSRC PhD studentship. A.N., A.S.C.R. and T.P. were funded by a Wellcome Trust Strategic Award (London Pain Consortium; ref. 083259). A.S.C.R. and W.H. were funded by the Innovative Medicines Initiative Joint Undertaking (Europain; grant agreement no. 115007). We thank Pfizer for providing stavudine. Conflicts of interest None declared. Funded by BBSRC PhD studentship Wellcome Trust Strategic Award. Grant Number: 083259 Innovative Medicines Initiative Joint Undertaking. Grant Number: 115007

PY - 2015/2

Y1 - 2015/2

N2 - 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 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 expressionsmall- 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 patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug-associated NP.

AB - 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 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 expressionsmall- 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 patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug-associated NP.

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DO - 10.1002/ejp.541

M3 - Article

C2 - 25070481

SN - 1090-3801

VL - 19

SP - 236

EP - 245

JO - European Journal of Pain

JF - European Journal of Pain

IS - 2

ER -

Heterogeneous responses of dorsal root ganglion neurons in neuropathies induced by peripheral nerve trauma and the antiretroviral drug stavudine

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