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

Abstract

Disc afferent nerve fiber Low back pain In vivo single nerve recording Dynamic weight bearing Morphine s u m m a r y 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 ¼ 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 ¼ 20) were assessed by Western blot. LBP-related behaviour (n ¼ 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 ¼ 19) and painful behaviour (n ¼ 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, 1,500e3,000 mm Hg), strong upregulation of NGF (200e250 % 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 mM) or systemic (3 mg kg À1) 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.

Effect of Directional Deep Brain Stimulation on Sensory Thresholds in Parkinson’s Disease

“…VFF testing is a well-validated means of mechanical threshold testing and here fibers range from a force of 0.008 to 300 g of pressure (Scitech Korea, Inc., Seoul, South Korea). VFF have shown efficacy in quantifying mechanical sensitivity in previous studies involving both human and animal models (Belasen et al, 2017;Park et al, 2019). The Neuropen is a standardized 10-and 40-g weighted pinprick device.…”

Gut-disc axis: A cause of intervertebral disc degeneration and low back pain?

“…Notably, the migration of immune cells into the IVD stimulates the IVD cells to generate neurogenic factors, e.g. brain-derive neurotrophic factor (BDNF) and nerve growth factor (NGF) [45,56,57]. This induces the appearance of nociceptive nerve fibres in the IVD as well as dorsal root ganglion (DRG).…”

Injectable decellularized nucleus pulposus tissue exhibits neuroinhibitory properties

“… 4 , 5 These nerve fibers are stimulated and sensitized by the catabolic disc environment. 6 , 7 The current gold standard of treatment for end‐stage chronic LBP patients is a spinal fusion, which can be invasive, have high complication rates (14.3% 8 ‐16% 9 of patients), high costs, 8 , 9 , 10 long recovery times, 11 and lead to reduced range of motion and increased potential for adjacent level degeneration. 12 , 13 An alternative low‐risk treatment that focuses on reducing a patient's pain holds great potential for the treatment of LBP.…”