Spinal cord sensitization following lumbar endplate microfracture – An In Vivo Rat Model — The International Society for the Study of the Lumbar Spine
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  2. SESSION #8 - MODIC CHANGE AND SPINAL CORD SENSITIZATION
  3. Spinal cord sensitization following lumbar endplate microfracture – An In Vivo Rat Model

Spinal cord sensitization following lumbar endplate microfracture – An In Vivo Rat Model (#41)

Alon Lai 1 , Kashaf Zaheer 1 2 , Dalin Wang 1 3 , Damien M Laudier 1 , Venetia Zachariou 4 , James C Iatridis 1
  1. Icahn School of Medicine at Mount Sinai, New York, NY, United States
  2. Vassar College, Poughkeepsie, NY
  3. Department of Spine Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
  4. Nash Family Department of Neuroscience, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Introduction

Intervertebral disc (IVD) degeneration is highly associated with chronic back pain. Dorsal-root-ganglia (DRG) of peripheral nervous system are reported to be sensitized with upregulation of neuropeptides and pro-inflammatory cytokines from IVD degeneration [1-4]. Animal models are needed to better understand pathophysiological transition from acute spinal injury to chronic pain, and to screen therapeutics. This study identified cross-talk between IVD degeneration and spinal cord by measuring substance P (SubP), a common neurotransmitter in the nervous system, following endplate (EP) microfracture injury-induced IVD degeneration in an in-vivo rat model.

 

Method

Procedures were IACUC approved. Nineteen male five-month-old Sprague-Dawley rats underwent sham (n=6) or EP injury surgery (n=13). In EP injury groups, L4-5 and L5-6 IVDs were punctured obliquely through their proximal vertebral body using K-wire, and injected with either tumor necrosis factor-alpha (TNFα) (n=7) or PBS (n=6). Back pain-related behaviors (i.e. hindpaw mechanical allodynia and forepaw grip force) were tested biweekly. At 8-weeks after injury, all rats were euthanized after taking radiograph for IVD height measurement. Lumbar spinal cord (corresponding to vertebral level T12-L1) was isolated, and stained for substance P (SubP) using immunohistochemistry with Nissl stain to visualize spinal cord neurons. SubP-immunoreactivity (SubP-ir) area relative to spinal dorsal horn compared between groups.

 

Results

SubP was found in laminae I-II of spinal cord (Fig1A). SubP-ir area in trended to be higher in both EP injury groups compared to Sham (Fig1B). SubP-ir area was significantly correlated with pain-like behaviors including the peak and average grip force, and had statistical trends in association with von Frey hindpaw withdrawal threshold, and IVD height (Fig1C).

 

Discussion

This is the first study to demonstrates that EP-injury driven IVD degeneration results in spinal cord sensitization with increased SubP in the dorsal horn of spinal cord in rats 8 weeks after EP injury. The SubP in the spinal cord were mainly localized to laminae I and II where terminations of nociceptive A-delta and C nerve fibers occur [5]. Increased spinal cord SubP was previously reported in animal models of neuropathic pain and inflammation [6-9], suggesting that EP-injury in this study may involve a combination of inflammatory and neuropathic conditions needing further characterization. SubP-ir was significantly correlated with pain-like behaviors as well as IVD height loss in this model suggesting cross-talk between spinal cord and IVD following EP injury, that results in increased pain-like behaviors. These multiple associations across tissues and behaviors observed in this study have clinical implications suggesting that treatment strategies for chronic discogenic pain may require interventions targeting both IVD and neural pathologies.

 

Acknowledgements: Funded by NIH grants R01AR057397, R01AR078857, and R01EB019980.

 

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