Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model

Magali Millecamps, Jan T. Czerminski, Axel P. Mathieu, Laura S. Stone

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Background Context Chronic low back pain is debilitating and difficult to treat. Depending on the etiology, responses to treatments vary widely. Although chronic low back pain is frequently related to intervertebral disc degeneration, the relationship between disc degeneration severity and clinical symptoms are still poorly understood. In humans, studies investigating the relationship between disc degeneration severity and low back pain are limited by the difficulty of obtaining disc samples from well-characterized patients and pain-free controls. We have previously described the secreted protein, acidic, rich in cysteine (SPARC)-null mouse model of chronic low back pain. SPARC is a matricellular protein involved in regulating the assembly and composition of extracellular matrix. The SPARC-null mice develop age-dependent disc degeneration of increasing severity accompanied by behavioral signs suggestive of axial low back pain, radiating leg pain, and motor impairment. The existence of this model allows for examination of the relationships between clinical symptoms in vivo and pathological signs of disc degeneration ex vivo. Purpose The goal of this study was to explore the relationship between behavioral signs of pain and the severity of lumbar disc degeneration using the SPARC-null mouse model of disc degeneration-related low back pain. Study Design This study used a cross-sectional, multiple-cohort behavioral and histological study of disc degeneration and behavioral symptoms in a mouse model of low back pain associated with disc degeneration. Methods SPARC-null and wild-type control mice ranging from 6 to 78 weeks of age were used in this study. The severity of disc degeneration was determined by ex vivo analysis of the lumbar spine using colorimetric histological staining and a scoring system adapted from the Pfirrmann scale. Behavioral signs of axial low back pain, radiating leg pain, and motor impairment were quantified as tolerance to axial stretching in the grip force assay, hypersensitivity to cold or mechanical stimuli on the hindpaw (acetone and von Frey tests), and latency to fall in the rotarod assay, respectively. Results The SPARC-null mice exhibited decreased tolerance to axial stretching, hindpaw cold hypersensitivity, and motor impairment compared with age-matched control mice. The severity of disc degeneration increased with age in both SPARC-null and control mice and by 78 weeks of age, the same proportion of lumbar discs were abnormal in SPARC-null and control mice. However, the degree of degeneration was more severe in the SPARC-null mice. In both SPARC-null and control mice, tolerance to axial stretching but not hindpaw cold sensitivity correlated with disc degeneration severity. Motor impairment correlated with degeneration severity in the SPARC-null mice only. Conclusions These data suggest that internal disc disruption contributes to axial low back pain and motor impairment but not to radiating leg pain. These results have implications for the optimization of mechanism-based treatments strategies.

Original languageEnglish (US)
Pages (from-to)2524-2537
Number of pages14
JournalSpine Journal
Volume15
Issue number12
DOIs
StatePublished - Dec 1 2015

Bibliographical note

Funding Information:
Author disclosures: MM: Grants: Canadian Institutes for Health Research operating grant (F, Paid directly to institution/employer); American Pain Society award: future leader in pain research (C, Paid directly to institution/employer). JTC: Nothing to disclose. APM: Nothing to disclose. LSS: Grants: Canadian Institutes for Health Research operating grant (F, Paid directly to institution/employer); CIHR/CPS/AstraZeneca Biology of Pain Young Investigator Grant (F, Paid directly to institution/employer); Fonds de la recherche en santé du Québec Bourse de chercheur-boursier (F, Paid directly to institution/employer).

Funding Information:
This study was supported by a CIHR/CPS/AstraZeneca Biology of Pain Young Investigator Grant XCP-83755 to LSS, CIHR operating grants MOP-102586 and MOP-126046 to LSS and MM, a pain research grant from The Louise and Alan Edwards Foundation to LSS, MM, and AM, aide for research services from the Quebec Network for Oral and Bone Health Research to LSS, a Fonds de la recherche en santé du Québec Bourse de chercheur-boursier to LSS, and an American Pain Society Future Leaders in Pain Research Award to MM.

Keywords

  • Animal model
  • Correlation
  • Degenerative disc disease
  • Histology
  • Intervertebral disc
  • Low back pain
  • SPARC

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