Involvement between social defeat stress and pain-related behavior in a rat lumbar disk herniation model



Psychological and social factors are involved in the disability and chronicity of pain. Our study aim was to investigate whether social defeat stress (SDS) as a psychophysical stress affected mechanical withdrawal thresholds in the lumbar disk herniation (LDH) rat model. Changes in microglia and astrocytes, which play important roles in neuropathic pain states, were also investigated.

Materials and methods

For the LDH model, nucleus pulposus (NP) was applied to the L5 dorsal root ganglion (DRG) in adult female Sprague–Dawley rats. SDS was performed 15 min daily for 8 days. Mechanical withdrawal thresholds were measured, and immunoreactive cells of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (Iba-1), which were used as markers of microglia, satellite glial cells, and astrocytes, were assessed in the DRG, spinal cord (SC), and ventrolateral periaqueductal gray matter (VLPAG).


Mechanical withdrawal thresholds decreased in the NP group for 21 days and for 35 days in the NP + SDS group. Expression of GFAP and Iba-1 in the DRG and SC increased up to day 21 in the NP and NP + SDS groups. In the sham + SDS and NP + SDS groups, expression of GFAP in the VLPAG decreased until day 35.


SDS prolongs mechanical allodynia induced by NP. Changes of GFAP expression in the VLPAG were associated with mechanical allodynia of the NP + SDS group during the late phase. These results suggest that psychological chronic stress might delay recovery from mechanical allodynia induced by the LDH model.

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The authors thank Akira Sato for his technical assistance.

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Correspondence to Miho Sekiguchi.

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IRB approval/Research Ethics Committee: There are no potential conflicts of interest in this study.

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The animal experiments were carried out under the supervision of the Animal Care and Use Committee in accordance with the Guidelines for Animal Experiments of our institution and the Government Law Concerning the Protection and Control of Animals.

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Yomogida, S., Sekiguchi, M. & Konno, Si. Involvement between social defeat stress and pain-related behavior in a rat lumbar disk herniation model. Eur Spine J 29, 2431–2440 (2020).

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  • Lumbar disk herniation
  • Neuropathic pain
  • Social defeat stress
  • Periaqueductal gray matter
  • Glial fibrillary acidic protein