Abstract
Low back pain is more common in women than men, yet most studies of intervertebral disc (IVD) degeneration do not address sex differences. In humans, there are sex differences in spinal anatomy and degenerative changes in biomechanics, and animal models of chronic pain have demonstrated sex differences in pain transduction. However, there are few studies investigating sex differences in annular puncture IVD degeneration models. IVD puncture is known to result in progressive biomechanical alterations, but whether these IVD changes correlate with pain is unknown. This study used a rat IVD injury model to determine if sex differences exist in mechanical allodynia, biomechanics, and the relationship between them, six weeks after IVD injury.
Procedures were IACUC approved. 24 male & 24 female four-month-old Sprague-Dawley rats underwent a sham or annular puncture injury surgery (n=12 male, 12 female). In injury groups, three lumbar IVDs were each punctured three times with a needle, and injected with tumor necrosis factor-alpha. Mechanical allodynia was tested biweekly using von Frey filaments. Six weeks after IVD injury, rats were euthanized and motion segments were dissected for non-destructive axial tension-compression and torsional rotation biomechanical testing. Two-way ANOVA with Bonferroni corrections identified statistically significant differences (p < 0 .05) and correlations used Pearson's coefficient.
Annular puncture injury induced a significant increase in mechanical allodynia compared to sham in male but not female rats up to six weeks after injury. There was a significant sex effect on both torque range and torsional stiffness, with males exhibiting greater stiffness and torque range than females. Tensile stiffness, compressive stiffness, and axial range of motion showed no sex difference. Males and females showed similar patterns of correlation between variables when sham and injury groups were analyzed together, but correlations were stronger in males. Most correlations were clustered within testing approach: axial biomechanics negatively correlated, torsional biomechanics positively correlated, and von Frey thresholds positively correlated. Surprisingly, mechanical allodynia did not correlate with any biomechanics after injury, and the axial and torsional biomechanics showed little correlation.
This study demonstrates that males and females respond to IVD injury differently. Given the absence of correlation between pain and biomechanics, pain cannot be attributed completely to biomechanical changes. This may explain why spinal fusion surgery, an intervention limited to the spine, has produced inconsistent results and is controversial for patients with low back pain. Thus, in addressing low back pain, we must consider both spinal tissues and the nervous system. Further, the limited correlation between axial and torsional biomechanics indicates that IVD injury may have distinct effects on nucleus pulposus and annulus fibrosus. Biomechanics did not differ between sham and injury at week six, suggesting healing after injury. It remains possible that acute biomechanical changes may initiate chronic pain pathogenesis. We conclude that the observed sex differences demonstrate the need for inclusion of both males and females in IVD injury and pain studies, and suggest that males and females may require different treatments for conditions that appear similar.
