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Does Norepinephrine Influence Pain Behavior Mediated by Dorsal Root Ganglia?: A Pilot Study

  • Basic Research
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Postganglionic neurons in the sympathetic nervous system reportedly are involved in lumbar radicular pain and release norepinephrine (NE), a neurotransmitter. Increased numbers of sympathetic nerve fibers have been found in dorsal root ganglion (DRG) neurons in a root constriction model. Whether this is a reasonable model for pain, however, is unclear

Questions/purposes

We asked whether: (1) painful behaviors occurred in the root constriction model; (2) NE enhanced the excitability of DRG neurons in the root constriction model; and (3) which adrenoceptors were related to the mediation of the NE effects.

Methods

The L5 root was sutured proximal to the DRG as the root constriction model. Behavioral tests were performed until 28 days after surgery. At 10 to 14 days after the root constriction, DRG neurons were quickly excised and digested with collagenase for electrophysiologic studies. Action potentials were recorded from single DRG neurons using a whole-cell patch clamp technique. NE (10 μmol/L) was directly applied to the DRG neurons. The adrenergic sensitivity was examined in combination with antagonists.

Results

The rats with root constriction exhibited painful behavior. NE increased the excitability of DRG neurons in the root constriction model. The effects of NE were inhibited by pretreatment with an α-antagonist and α2-antagonist but not an α1-antagonist.

Conclusions

Our observations suggest NE plays an important role in generating lumbar radicular pain mainly via α2-adrenoceptors.

Clinical Relevance

An α2-antagonist may be an appropriate agent for trials to treat lumbar radicular pain.

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Acknowledgments

We thank Takehito Iwase for performing the behavioral studies and Dr. Takashi Kirita, Dr. Satoshi Mizuno, and Dr. Yoshinori Terashima for technical assistance related to the electrophysiologic experiments.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan

    Katsumasa Tanimoto MD, PhD, Tsuneo Takebayashi MD, PhD & Toshihiko Yamashita MD, PhD

  2. Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan

    Takeshi Kobayashi MD, PhD & Noritsugu Tohse MD, PhD

Authors
  1. Katsumasa Tanimoto MD, PhD
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  2. Tsuneo Takebayashi MD, PhD
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  3. Takeshi Kobayashi MD, PhD
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  4. Noritsugu Tohse MD, PhD
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  5. Toshihiko Yamashita MD, PhD
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Corresponding author

Correspondence to Katsumasa Tanimoto MD, PhD.

Additional information

One or more of the authors (TT, NT, and TY) have received funding from a research grant for the Grant-in-Aid for Science Research (B) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grant Number of 19390398) and the JOA-Subsidized Science Project Research 2007-8.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at Sapporo Medical University, Sapporo, Japan.

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Tanimoto, K., Takebayashi, T., Kobayashi, T. et al. Does Norepinephrine Influence Pain Behavior Mediated by Dorsal Root Ganglia?: A Pilot Study . Clin Orthop Relat Res 469, 2568–2576 (2011). https://doi.org/10.1007/s11999-011-1798-x

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  • DOI: https://doi.org/10.1007/s11999-011-1798-x

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