• Seiji Kimura, Yoshihiro Sakuma, Miyako Suzuki, Sumihisa Orita, Kazuyo Yamauchi, Gen Inoue, Yasuchika Aoki, Tetsuhiro Ishikawa, Masayuki Miyagi, Hiroto Kamoda, Go Kubota, Yasuhiro Oikawa, Kazuhide Inage, Takeshi Sainoh, Jun Sato, Junichi Nakamura, Tomoaki Toyone, Kazuhisa Takahashi, and Seiji Ohtori.
• From the Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
• Spine. 2014 Mar 15;39(6):455-62.

Study DesignAnimal study.ObjectiveTo evaluate pain behavior and neuropeptide changes in the spinal dorsal horn after sciatic nerve compression and application of nucleus pulposus (NP) in rats.Summary Of Background DataThe pathomechanisms of lumbar disc herniation pain have not been fully elucidated. Pain-associated neuropeptides, including substance P and calcitonin gene-related peptide (CGRP), are produced in dorsal root ganglion neurons and transported to spinal dorsal horn nerve terminals where they function in pain transmission. However, changes in CGRP-immunoreactive (IR) sensory nerve terminals have not been reported in models of disc herniation. This study evaluated pain-related behavior and changes in CGRP-IR terminals in the spinal dorsal horn after combined sciatic nerve compression and NP application.MethodsFive groups of rats underwent either sciatic nerve compression with NP (n = 20), application of NP only (n = 20), nerve compression only (n = 20), and sham operation with neither compression nor NP (n = 20) or no operation (controls, n = 20). Mechanical hyperalgesia was measured every second day for 3 weeks. CGRP-IR terminals in each spinal dorsal horn lamina were examined 7 and 14 days postsurgery. Pain behavior and CGRP immunoreactivity were compared among the 5 groups.ResultsMechanical hyperalgesia was found in the NP only, nerve compression only, and the NP with nerve compression groups (P ≤ 0.05). CGRP-IR nerve terminals in the superficial laminae (I and II) and the deep laminae (III-VI) significantly increased in the NP only, nerve compression only, and NP with nerve compression groups compared with control and sham groups (P ≤ 0.05). Significant mechanical hyperalgesia and increased CGRP-IR nerve terminals were found in the NP with nerve compression group compared with the NP only and nerve compression only groups (P ≤ 0.05).ConclusionOur results indicate that nerve compression plus NP application produces the most pain-related behavior. CGRP-IR nerve terminals increased in laminae I and II that transmit pain and in laminae III to VI that transmit proprioception. Findings suggest that nerve compression plus NP application induces changes in CGRP expression in the superficial and deep laminae, and these changes are partly responsible for disc herniation pain.

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