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Differences in Damage to CGRP Immunoreactive Sensory Nerves After Two Lumbar Surgical Approaches: Investigation Using Humans and Rats

Ohtori, Seiji MD, PhD; Miyagi, Masayuki MD; Takaso, Masashi MD, PhD; Inoue, Gen MD, PhD; Orita, Sumihisa MD, PhD; Eguchi, Yawara MD, PhD; Ochiai, Nobuyasu MD, PhD; Kishida, Shunji MD, PhD; Kuniyoshi, Kazuki MD, PhD; Nakamura, Junichi MD, PhD; Aoki, Yasuchika MD, PhD; Ishikawa, Tetsuhiro MD; Arai, Gen MD; Kamoda, Hiroto MD; Suzuki, Miyako MD; Toyone, Tomoaki MD, PhD; Takahashi, Kazuhisa MD, PhD

doi: 10.1097/BRS.0b013e31821258f7
Basic Science

Study Design. Immunohistochemical study.

Objective. To evaluate invasive surgical approaches by analyzing the number of sensory nerve fibers at 2 back muscle sites in rats and humans and the number of injured nerve fibers innervating these 2 sites after muscle injury in rats.

Summary of Background Data. Several minimally invasive approaches have recently become popular in the treatment of lumbar spine disorders. Minimally invasive surgery (MIS) is not invasive to back muscle and is thought to reduce low back pain. Muscle damage has been generally evaluated by magnetic resonance imaging (MRI); however, damage to sensory nerve fibers in and around back muscle that is directly related to pain has apparently not been explored.

Methods. Human muscle at L4–L5 was obtained from the paraspinous process (during a midline approach) and from paraspinal back muscle (during a Wiltse paraspinal approach) (n = 10 each). The muscle was sectioned and immunostained for calcitonin gene-related peptide (CGRP). To detect dorsal root ganglion (DRG) neurons innervating back muscle in rats, Fluoro-Gold (FG) was applied to the same 2 sites on the lower back muscle at L4–L5 (only application, n = 12; application of FG + muscle injury, n = 12). DRGs were harvested and immunostained for CGRP and activating transcription factor-3 (ATF-3: marker for nerve injury). The numbers of FG-labeled CGRP-immunoreactive or FG-labeled ATF-3-immunoreactive DRG neurons innervating the 2 sites were counted and compared.

Results. CGRP-immunoreactive sensory nerve fibers were found at the 2 sites. The average number of CGRP-immunoreactive sensory nerve fibers in muscle obtained in a midline approach was significantly higher than that in muscle obtained in a Wiltse paraspinal approach (P < 0.01). The numbers of FG-labeled CGRP- and ATF-3-immunoreactive DRG neurons innervating paraspinous process muscle were significantly greater than those innervating paraspinal back muscle in rats (P < 0.01).

Conclusion. There are more CGRP-immunoreactive sensory nerve fibers and DRG neurons innervating muscle in the midline approach area than in the Wiltse paraspinal approach area in humans and rats. There are more ATF-3-immunoreactive DRG neurons innervating muscle in the midline approach area than in the Wiltse paraspinal approach area after muscle injury in rats. This result may show the differences in sensory nerve injury during the 2 surgical approaches.

In humans and rats, more calcitonin gene-related peptide-immunoreactive neurons innervated muscle in midline than in Wiltse paraspinal approach areas. In rats, sensory nerve injury after muscle injury was significantly greater after a midline than Wiltse paraspinal approach. This may show the differences in sensory nerve injury during two surgical approaches.

From the Department of Orthopaedic Surgery, Chiba University, Chuo-ku, Chiba, Japan

Address correspondence and reprint requests to Seiji Ohtori, MD, PhD, Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; E-mail:

Acknowledgment date: June 29, 2010. First revision date: November 8, 2010. Second revision date: December 20, 2010. Acceptance date: January 22, 2011.

The manuscript submitted does not contain information about medical device(s)/drug(s).

No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

© 2012 Lippincott Williams & Wilkins, Inc.