Comparison of dorsal root ganglion gene expression in rat models of traumatic and HIV-associated neuropathic pain.
To elucidate the mechanisms underlying peripheral neuropathic pain in the context of HIV infection and antiretroviral therapy, we measured gene expression in dorsal root ganglia (DRG) of rats subjected to systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) and concomitant delivery of HIV-gp120 to the rat sciatic nerve. L4 and L5 DRGs were collected at day 14 (time of peak behavioural change) and changes in gene expression were measured using Affymetrix whole genome rat arrays. Conventional analysis of this data set and Gene Set Enrichment Analysis (GSEA) was performed to discover biological processes altered in this model. Transcripts associated with G protein coupled receptor signalling and cell adhesion were enriched in the treated animals, while ribosomal proteins and proteasome pathways were associated with gene down-regulation. To identify genes that are directly relevant to neuropathic mechanical hypersensitivity, as opposed to epiphenomena associated with other aspects of the response to a sciatic nerve lesion, we compared the gp120+ddC-evoked gene expression with that observed in a model of traumatic neuropathic pain (L5 spinal nerve transection), where hypersensitivity to a static mechanical stimulus is also observed. We identified 39 genes/expressed sequence tags that are differentially expressed in the same direction in both models. Most of these have not previously been implicated in mechanical hypersensitivity and may represent novel targets for therapeutic intervention. As an external control, the RNA expression of three genes was examined by RT-PCR, while the protein levels of two were studied using western blot analysis.
Maratou
Klio
K
Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London, UK.
Wallace
Victoria C J
VC
Hasnie
Fauzia S
FS
Okuse
Kenji
K
Hosseini
Ramine
R
Jina
Nipurna
N
Blackbeard
Julie
J
Pheby
Timothy
T
Orengo
Christine
C
Dickenson
Anthony H
AH
McMahon
Stephen B
SB
Rice
Andrew S C
AS
D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000235:genetics*; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000150:complications*; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013127:Spinal Nerves / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D014162:Transfection; D016047:Zalcitabine / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D018894:Reverse Transcriptase Inhibitors; D016047:Zalcitabine