HSV-mediated Expression of Interleukin-4 in Dorsal Root Ganglion Neurons Reduces Neuropathic Pain

Overview

Journal Mol Pain

Date 2006 Mar 1

PMID 16503976

Citations 67

Authors

Shuanglin Hao

Marina Mata

Joseph C Glorioso

David J Fink

Affiliations

Soon will be listed here.

Abstract

Background: To examine the role of inflammatory mediators in neuropathic pain, we used a replication-defective genomic herpes simplex virus (HSV)-based vector containing the coding sequence for the anti-inflammatory peptide interleukin (IL)-4 under the transcriptional control of the HSV ICP4 immediate early promoter, vector S4IL4, to express IL-4 in dorsal root ganglion (DRG) neurons in vivo.

Results: Subcutaneous inoculation of S4IL4 in the foot transduced lumbar DRG to produce IL-4. Transgene-mediated expression of IL-4 did not alter thermal latency or tactile threshold in normal animals, but inoculation of S4IL4 1 week after spinal nerve ligation (SNL) reduced mechanical allodynia and reversed thermal hyperalgesia resulting from SNL. Inoculation of S4IL4 1 week before SNL delayed the development of thermal hyperalgesia and tactile allodynia, but did not prevent the ultimate development of these manifestations of neuropathic pain. S4IL4 inoculation suppressed non-noxious-induced expression of c-Fos immunoreactivity in dorsal horn of spinal cord and reversed the upregulation of spinal IL-1beta, PGE2, and phosphorylated-p38 MAP kinase, characteristic of neuropathic pain.

Conclusion: HSV-mediated expression of IL-4 effectively reduces the behavioral manifestations of neuropathic pain, and reverses some of the biochemical and histologic correlates of neuropathic pain at the spinal level.

Citing Articles

Gene therapy for chronic pain management.

Li Y, Ji R Cell Rep Med. 2024; 5(10):101756.

PMID: 39366385 PMC: 11513853. DOI: 10.1016/j.xcrm.2024.101756.

Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain: an update.

Berta T, Strong J, Zhang J, Ji R Expert Opin Ther Targets. 2023; 27(8):665-678.

PMID: 37574713 PMC: 10530032. DOI: 10.1080/14728222.2023.2247563.

The involvement of immune system in intervertebral disc herniation and degeneration.

Ye F, Lyu F, Wang H, Zheng Z JOR Spine. 2022; 5(1):e1196.

PMID: 35386754 PMC: 8966871. DOI: 10.1002/jsp2.1196.

Interferons in Pain and Infections: Emerging Roles in Neuro-Immune and Neuro-Glial Interactions.

Tan P, Ji J, Yeh C, Ji R Front Immunol. 2021; 12:783725.

PMID: 34804074 PMC: 8602180. DOI: 10.3389/fimmu.2021.783725.

Immunological mechanism of postherpetic neuralgia and effect of pregabalin treatment on the mechanism: a prospective single-arm observational study.

Mercan A, Tuncer Uzun S, Keles S, Hacibeyoglu G, Yilmaz R, Reisli R Korean J Pain. 2021; 34(4):463-470.

PMID: 34593664 PMC: 8494950. DOI: 10.3344/kjp.2021.34.4.463.

References

Paul W . Interleukin-4: a prototypic immunoregulatory lymphokine. Blood. 1991; 77(9):1859-70. View

Catheline G, Le Guen S, Besson J . Intravenous morphine does not modify dorsal horn touch-evoked allodynia in the mononeuropathic rat: a Fos study. Pain. 2001; 92(3):389-398. DOI: 10.1016/S0304-3959(01)00283-4. View

Cui J, Holmin S, Mathiesen T, Meyerson B, Linderoth B . Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy. Pain. 2000; 88(3):239-248. DOI: 10.1016/S0304-3959(00)00331-6. View

Vale M, Marques J, Moreira C, Rocha F, Ferreira S, Poole S . Antinociceptive effects of interleukin-4, -10, and -13 on the writhing response in mice and zymosan-induced knee joint incapacitation in rats. J Pharmacol Exp Ther. 2002; 304(1):102-8. DOI: 10.1124/jpet.102.038703. View

Sweitzer S, Martin D, DeLeo J . Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain. Neuroscience. 2001; 103(2):529-39. DOI: 10.1016/s0306-4522(00)00574-1. View

Liu J, Wolfe D, Hao S, Huang S, Glorioso J, Mata M . Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain. Mol Ther. 2004; 10(1):57-66. DOI: 10.1016/j.ymthe.2004.04.017. View

DeLeo J, Rutkowski M, Stalder A, Campbell I . Transgenic expression of TNF by astrocytes increases mechanical allodynia in a mouse neuropathy model. Neuroreport. 2000; 11(3):599-602. DOI: 10.1097/00001756-200002280-00033. View

BRAZ J, Beaufour C, Coutaux A, Epstein A, Cesselin F, Hamon M . Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin overproduction in sensory neurons. J Neurosci. 2001; 21(20):7881-8. PMC: 6763863. View

Hao S, Mata M, Wolfe D, Huang S, Glorioso J, Fink D . HSV-mediated gene transfer of the glial cell-derived neurotrophic factor provides an antiallodynic effect on neuropathic pain. Mol Ther. 2003; 8(3):367-75. DOI: 10.1016/s1525-0016(03)00185-0. View

10.

Ji R, Samad T, Jin S, Schmoll R, Woolf C . p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron. 2002; 36(1):57-68. DOI: 10.1016/s0896-6273(02)00908-x. View

11.

Sommer C, Kress M . Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004; 361(1-3):184-7. DOI: 10.1016/j.neulet.2003.12.007. View

12.

Kim S, Chung J . An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992; 50(3):355-363. DOI: 10.1016/0304-3959(92)90041-9. View

13.

Laughlin T, Bethea J, Yezierski R, Wilcox G . Cytokine involvement in dynorphin-induced allodynia. Pain. 2000; 84(2-3):159-67. DOI: 10.1016/s0304-3959(99)00195-5. View

14.

Hao S, Mata M, Goins W, Glorioso J, Fink D . Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain. Pain. 2003; 102(1-2):135-42. DOI: 10.1016/s0304-3959(02)00346-9. View

15.

Puskovic V, Wolfe D, Goss J, Huang S, Mata M, Glorioso J . Prolonged biologically active transgene expression driven by HSV LAP2 in brain in vivo. Mol Ther. 2004; 10(1):67-75. DOI: 10.1016/j.ymthe.2004.04.004. View

16.

Chapman Jr H, Munger J, Shi G . The role of thiol proteases in tissue injury and remodeling. Am J Respir Crit Care Med. 1994; 150(6 Pt 2):S155-9. DOI: 10.1164/ajrccm/150.6_Pt_2.S155. View

17.

Goins W, Marconi P, Krisky D, Wolfe D, Glorioso J, Ramakrishnan R . Construction of replication-defective herpes simplex virus vectors. Curr Protoc Hum Genet. 2008; Chapter 12:Unit 12.11. DOI: 10.1002/0471142905.hg1211s33. View

18.

Arruda J, Sweitzer S, Rutkowski M, DeLeo J . Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain. Brain Res. 2000; 879(1-2):216-25. DOI: 10.1016/s0006-8993(00)02807-9. View

19.

Veeranna , Amin N, Ahn N, Jaffe H, Winters C, Grant P . Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. J Neurosci. 1998; 18(11):4008-21. PMC: 6792805. View

20.

Hao S, Takahata O, Mamiya K, Iwasaki H . Sevoflurane suppresses noxious stimulus-evoked expression of Fos-like immunoreactivity in the rat spinal cord via activation of endogenous opioid systems. Life Sci. 2002; 71(5):571-80. DOI: 10.1016/s0024-3205(02)01704-6. View