title: Evaluation of pain behavior and calcitonin gene-related peptide immunoreactive sensory nerve fibers in the spinal dorsal horn after sciatic nerve compression and application of nucleus pulposus in rats.
abstract: METHODS
  Animal study.
  
  
  OBJECTIVE
  To evaluate pain behavior and neuropeptide changes in the spinal dorsal horn after sciatic nerve compression and application of nucleus pulposus (NP) in rats.
  
  
  BACKGROUND
  The 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.
  
  
  METHODS
  Five 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.
  
  
  RESULTS
  Mechanical 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: From the Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kimura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Miyako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Sumihisa
authors.initials: S
authors.lastname: Orita
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamauchi
authors.forename: Gen
authors.initials: G
authors.lastname: Inoue
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Aoki
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyagi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kamoda
authors.forename: Go
authors.initials: G
authors.lastname: Kubota
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Inage
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sainoh
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.forename: Junichi
authors.initials: J
authors.lastname: Nakamura
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Toyone
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Seiji
authors.initials: S
authors.lastname: Ohtori
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D007150:Immunohistochemistry; D007405:Intervertebral Disc Displacement / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D009408:Nerve Compression Syndromes / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D010147:Pain Measurement; D058748:Pain Perception; D017288:Pain Threshold; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D013127:Spinal Nerves / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015740:Calcitonin Gene-Related Peptide