Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain

E. H. Park, S. W. Moon, H. R. Suh, S. Hochman, M. G. Lee, Y. I. Kim, I. T. Jang, Hee Chul Han

Research output: Contribution to journalArticle

Abstract

Objective: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). Design: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. Results: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500–3,000 mm Hg), strong upregulation of NGF (200–250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 μM) or systemic (3 mg kg−1) morphine administration. Conclusions: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.

Original languageEnglish
JournalOsteoarthritis and Cartilage
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Intervertebral Disc Degeneration
Intervertebral Disc
Low Back Pain
Nerve Fibers
Fibers
Nerve Growth Factor
Morphine
Walking
Rats
Animals
Bearings (structural)
Pressure
Weight-Bearing
Punctures
Hypersensitivity
Up-Regulation
Extremities
Animal Models
Western Blotting
Pain

Keywords

  • Disc afferent nerve fiber
  • Disc degeneration
  • Dynamic weight bearing
  • In vivo single nerve recording
  • Low back pain
  • Morphine

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

Cite this

Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain. / Park, E. H.; Moon, S. W.; Suh, H. R.; Hochman, S.; Lee, M. G.; Kim, Y. I.; Jang, I. T.; Han, Hee Chul.

In: Osteoarthritis and Cartilage, 01.01.2019.

Research output: Contribution to journalArticle

Park, E. H. ; Moon, S. W. ; Suh, H. R. ; Hochman, S. ; Lee, M. G. ; Kim, Y. I. ; Jang, I. T. ; Han, Hee Chul. / Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain. In: Osteoarthritis and Cartilage. 2019.
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abstract = "Objective: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). Design: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. Results: Compared to those with sham or na{\"i}ve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500–3,000 mm Hg), strong upregulation of NGF (200–250 {\%} increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 μM) or systemic (3 mg kg−1) morphine administration. Conclusions: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.",
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AU - Park, E. H.

AU - Moon, S. W.

AU - Suh, H. R.

AU - Hochman, S.

AU - Lee, M. G.

AU - Kim, Y. I.

AU - Jang, I. T.

AU - Han, Hee Chul

PY - 2019/1/1

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AB - Objective: We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP). Design: Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed. Results: Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500–3,000 mm Hg), strong upregulation of NGF (200–250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 μM) or systemic (3 mg kg−1) morphine administration. Conclusions: Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.

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KW - Low back pain

KW - Morphine

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