Gene transfer to interfere with TNFα signaling in neuropathic pain

Shuanglin Hao, M. Mata, J. C. Glorioso, D. J. Fink

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

We examined the role of spinal tumor necrosis factor-alpha (TNFα) in neuropathic pain of peripheral nerve origin. Two weeks after selective L5 spinal nerve ligation (SNL), rats exhibiting mechanical allodynia and thermal hyperalgesia showed a marked increase in full-length membrane-associated TNFα (mTNFα) in the dorsal horn of spinal cord, in the absence of detectable soluble TNFα peptide. Local release of the soluble p55 TNF receptor, achieved by herpes simplex virus vector-based gene transfer to dorsal root ganglion, resulted in a reduction of mTNFα and concomitant reductions in interleukin-1β and phosphorylated p38 MAP kinase. Subcutaneous inoculation of soluble p55 TNF receptor expressing HSV vector into the plantar surface of the hind foot ipsilateral to the ligation 1 week before SNL delayed the development of both mechanical allodynia and thermal hyperalgesia; subcutaneous inoculation into the hind foot ipsilateral to the ligation 1 week after SNL resulted in a statistically significant reduction in mechanical allodynia and thermal hyperalgesia that was apparent 1 week after inoculation. These results suggest a novel 'reverse signaling' through glial mTNFα, which may be exploited to downregulate the neuroimmune reaction in spinal cord to reduce chronic neuropathic pain.

Original languageEnglish
Pages (from-to)1010-1016
Number of pages7
JournalGene Therapy
Volume14
Issue number13
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

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Hyperalgesia
Neuralgia
Tumor Necrosis Factor-alpha
Ligation
Genes
Spinal Nerves
Tumor Necrosis Factor Receptors
Membranes
Foot
Spinal Ganglia
p38 Mitogen-Activated Protein Kinases
Simplexvirus
Interleukin-1
Peripheral Nerves
Neuroglia
Chronic Pain
Spinal Cord
Down-Regulation
Peptides

ASJC Scopus subject areas

  • Genetics

Cite this

Gene transfer to interfere with TNFα signaling in neuropathic pain. / Hao, Shuanglin; Mata, M.; Glorioso, J. C.; Fink, D. J.

In: Gene Therapy, Vol. 14, No. 13, 01.07.2007, p. 1010-1016.

Research output: Contribution to journalArticle

Hao, Shuanglin ; Mata, M. ; Glorioso, J. C. ; Fink, D. J. / Gene transfer to interfere with TNFα signaling in neuropathic pain. In: Gene Therapy. 2007 ; Vol. 14, No. 13. pp. 1010-1016.
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