Current Gene Therapy using Viral Vectors for Chronic Pain

Abstract

The complexity of chronic pain and the challenges of pharmacotherapy highlight the importance of development of new approaches to pain management. Gene therapy approaches may be complementary to pharmacotherapy for several advantages. Gene therapy strategies may target specific chronic pain mechanisms in a tissue-specific manner. The present collection of articles features distinct gene therapy approaches targeting specific mechanisms identified as important in the specific pain conditions. Dr. Fairbanks group describes commonly used gene therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector (AAV)), and addresses biodistribution and potential neurotoxicity in pre-clinical models of vector delivery. Dr. Tao group addresses that downregulation of a voltage-gated potassium channel (Kv1.2) contributes to the maintenance of neuropathic pain. Alleviation of chronic pain through restoring Kv1.2 expression in sensory neurons is presented in this review. Drs Goins and Kinchington group describes a strategy to use the replication defective HSV vector to deliver two different gene products (enkephalin and TNF soluble receptor) for the treatment of post-herpetic neuralgia. Dr. Hao group addresses the observation that the pro-inflammatory cytokines are an important shared mechanism underlying both neuropathic pain and the development of opioid analgesic tolerance and withdrawal. The use of gene therapy strategies to enhance expression of the anti-pro-inflammatory cytokines is summarized. Development of multiple gene therapy strategies may have the benefit of targeting specific pathologies associated with distinct chronic pain conditions (by Guest Editors, Drs. C. Fairbanks and S. Hao).

Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality

“…Gene therapy research in promising areas, such as olfaction and pain, is growing and in many cases also explores the utility of AAV, most often using local routes of administration (Guedon et al, 2015;Williams et al, 2017).…”

TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons

“…HSV has been used as the delivery vehicle for the transduction of targeted genes, particularly for those that are more than 3 kb in molecular weight, in the preclinical animal models [28][29][30][31][32] and clinical trials [33]. However, it is unknown which types of DRG cells are transduced by HSV after either subcutaneous injection or nerve/DRG microinjection of HSV-GFP, as the injected HSV-GFP, unlike the injected AAV-GFP, cannot be observed in the DRG directly under the fluorescent microscope [28][29][30][31][32]. The present study used the immunostaining of anti-GFP antibody and a single-cell real-time RT-PCR assay of Gfp mRNA to firstly report that the microinjected HSV is limited to the microinjected DRG neurons and their fibers.…”

N/OFQ modulates orofacial pain induced by tooth movement through CGRP-dependent pathways

“…Lentivirus vector, a single-strand RNA with a length of 8 kb (49), is most suitable for the transduction of non-dividing cells, especially neurons and neural glial cells (50,51). The integration of viral gene into host genome on one hand is bene cial for stable expression, which makes it a promising gene therapeutic tool for a variety of pain conditions, especially for chronic pain (47,48,52). Our previous study revealed that administration of lentivirus containing TRPV1 shRNA aiming at knocking down TRPV1 was effective in alleviating orofacial pain (53).…”