Elsevier

The Spine Journal

Volume 14, Issue 10, 1 October 2014, Pages 2472-2478
The Spine Journal

Basic Science
Dorsal root ganglion electrical stimulation promoted intertransverse process spinal fusion without decortications and bone grafting: a proof-of-concept study

https://doi.org/10.1016/j.spinee.2014.04.001Get rights and content

Abstract

Background context

Periosteum, endosteum, and bone are innervated by sensory nerves expressing calcitonin gene-related peptide (CGRP), which is a known osteoanabolic peptide and plays an important role in fracture healing and spinal fusion. Synthesis and release of CGRP are found in sensory neurons located in the dorsal root ganglions (DRGs) and can be upregulated by electrical stimulation (ES) at DRG.

Purpose

To prove our study hypothesis on the potential of precise ES at DRG through implantable microelectrical stimulation system (IMESS) for its effect on promoting spinal fusion in a rat model without decortications and bone grafting.

Study design

An experimental animal study.

Methods

A novel IMESS was developed for stimulating L4–L6 DRG in rats. Sixteen rats were used and divided equally into the control group without ES and the ES group, with a daily 20 minutes ES to DRG for 6 weeks. At the end of 6 weeks, radiography and microcomputed tomography were conducted to evaluate new bone formation and spinal fusion. Bilateral L4–L6 DRGs were harvested for immunohistochemistry and quantification of neurons with upregulated CGRP expression.

Results

In the ES group, rate of radiographic fusion with complete and uninterrupted bony bridging was 100% (8/8) at the right L4/L5 transverse processes and 75% (6/8) at the right L5/L6 transverse processes. Bony callus formation was absent at the left L4–L6 transverse processes in the ES group and in bilateral L4–L6 transverse processes in the control group.

Conclusions

We proved for the first time that precise ES at DRG through IMESS effectively promoted intertransverse process fusion in rat model without decortications and bone grafting. Electrical stimulation at DRG might be an attractive minimal invasive bioengineering approach and an alternative therapy for intertransverse process fusion that is increasingly being used for the treatment of degenerative spine disorders.

Introduction

Lumbar spinal fusion is increasingly being used for the treatment of degenerative spine disorders, such as degenerative disc disease, spondylolisthesis, spondylosis, spinal stenosis, and scoliosis [1], [2]. Traditionally, spinal fusion can be achieved by decortications of articular surface and packing the joint space with bone grafts or biological substitutes [1], [2], [3], such as synthesized hydroxyapatite (HA) and bone morphogenetic proteins (BMPs) [4].

The present study was to test a concept of electrical stimulation (ES) at dorsal root ganglion (DRG) via an implantable microelectrical stimulation system (IMESS) to achieve an intertransverse process fusion without bone grafting in a rat model without decortications. In DRG, there are neurons synthesizing and releasing calcitonin gene-related peptide (CGRP) that is a sensory neuropeptide sharing the same gene complex encoding with calcitonin [5]. Calcitonin is produced when the gene is expressed in C cells in the thyroid, whereas the CGRP is produced when the same gene is expressed in sensory neurons located in the DRG and is transported peripherally. Numerous studies proved the distribution of CGRP receptors on the membrane of osteoblasts [5], [6], [7]. It was reported recently that CGRP stimulates BMP-2 expression and the differentiation of human osteoblast-like cells in vitro [8]. CGRP-expressing nerves are present in the periosteum, bone, and endosteum [9], [10]. Rapid proliferation of CGRP-expressing nerves has been observed during healing of rat tibial fracture [11], [12], [13]. The important role of CGRP in fracture healing has been evidenced by our findings that sciatic neurectomy in rat resulted in the absence of CGRP-expressing nerve fibers in the fracture site in tibia and delayed fracture healing [14]. Our group has also found rapid growth of CGRP-expressing nerves in spinal fusion callus in rabbit [15], [16].

Recent studies further showed that secretion of CGRP could be triggered by ES at DRG [17], [18], [19]. We have recently developed an IMESS that provides precise ES to target neurons in rats [20]. The purpose of this study was to examine DRG ES via IMESS for its potential in spinal fusion enhancement in a rat model.

Section snippets

Animals and experimental design

Sixteen Sprague-Dawley rats (female, 3-month-old, weight: 420–450 g) were equally randomly allocated into two groups (n=8 for each group), that is, the control group and the ES group. Electrical stimulation was applied at the right DRGs at the vertebral level L4–L6 of rats in the ES group. The experiment duration was 6 weeks. Dorsal root ganglion stimulation was provided via a set of IMESS implanted at the L4–L6 transverse processes. Rats were housed individually in metal cages and were allowed

Implantation of IMESS and electrical stimulation to DRG

All animals tolerated the implants and ES well. There was no postimplantation infection or edema at the surgery site and hind limbs.

Spinal fusion assessment

In the group ES, callus formation was spatially limited to the level of DRG stimulation between L4 and L6, posterior to transverse processes and pedicle (Fig. 4). The rate of radiographic fusion with complete and uninterrupted bony bridging was 100% (8/8) for the right L4/L5 transverse processes (Fig. 4) and was 75% (6/8) for the right L5/L6 transverse processes.

Discussion

In this study, we achieved a more than 75% solid fusion rate after 6 weeks of ES via IMESS to the DRG without decortications and grafting. The IMESS used in the present study was biocompatible and the parameters of ES were shown to be tolerable by animals. This result achieved in the present proof-of-concept study is very encouraging, as traditional posterolateral spinal fusion in a rat model has been reported to have 40% fusion rate with decortication and an autogenous bone or demineralized

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  • Cited by (8)

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    FDA device/drug status: Not applicable.

    Author disclosures: Y-CL: Nothing to disclose. Y-ML: Nothing to disclose. K-TP: Nothing to disclose. XQ: Nothing to disclose. H-WH: Grants: (RGC Ref.: N_PolyU537/10) and the National Natural Science Foundation of China (NSFC Ref: 51061160501). (F, Paid directly to institution). H-CZ: Grants: (RGC Ref.: N_PolyU537/10) and the National Natural Science Foundation of China (NSFC Ref: 51061160501). (F, Paid directly to institution). L-ML: Grants: (RGC Ref.: N_PolyU537/10) and the National Natural Science Foundation of China (NSFC Ref: 51061160501). (F, Paid directly to institution). XG: Grants: Research Grant Council Hong Kong(RGC Ref.: N_PolyU537/10) and the National Natural Science Foundation of China (NSFC Ref: 51061160501). (F, Paid directly to institution).

    The disclosure key can be found on the Table of Contents and at www.TheSpineJournalOnline.com.

    This study was supported by Research Grant Council of Hong Kong (Earmarked Research Grant PolyU N_PolyU537/10, HK$660,000), and National Natural Science Foundation of China (51061160501, RMB 330,000). No potential conflict of interest to disclose.

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