Spinal cord stimulation modulates supraspinal centers of the descending antinociceptive system in rats with unilateral spinal nerve injury

Molecular Pain

Takahisa Goto³  Kengo Funakoshi²  Hironobu Shinbori³  Yusuke Nakahashi⁴  Masahito Takiguchi²  Kensuke Saeki²  Ayako Kobayashi³  Yoshinori Kamiya¹  Toshiharu Tazawa⁴ 

[1] Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan;Department of Neuroanatomy, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan;Department of Anesthesiology, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan;Pain Mechanism Research Group, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan

关键词: Spinal cord stimulation;    Spinal cord;    Serotonergic pathway;    Noradrenergic pathway;    Neuropathic pain;    Locus coeruleus;    Dorsal raphe nucleus;    Descending antinociceptive system;   

Others  :  1217329
DOI  :  10.1186/s12990-015-0039-9

 received in 2015-02-28, accepted in 2015-06-11,  发布年份 2015

【 摘 要 】

Background

The descending antinociceptive system (DAS) is thought to play crucial roles in the antinociceptive effect of spinal cord stimulation (SCS), especially through its serotonergic pathway. The nucleus raphe magnus (NRM) in the rostral ventromedial medulla is a major source of serotonin [5-hydroxytryptamine (5-HT)] to the DAS, but the role of the dorsal raphe nucleus (DRN) in the ventral periaqueductal gray matter is still unclear. Moreover, the influence of the noradrenergic pathway is largely unknown. In this study, we evaluated the involvement of these serotonergic and noradrenergic pathways in SCS-induced antinociception by behavioral analysis of spinal nerve-ligated (SNL) rats. We also investigated immunohistochemical changes in the DRN and locus coeruleus (LC), regarded as the adrenergic center of the DAS, and expression changes of synthetic enzymes of 5-HT [tryptophan hydroxylase (TPH)] and norepinephrine [dopamine β-hydroxylase (DβH)] in the spinal dorsal horn.

Results

Intrathecally administered methysergide, a 5-HT ₁ - and 5-HT ₂ -receptor antagonist, and idazoxan, an α ₂ -adrenergic receptor antagonist, equally abolished the antinociceptive effect of SCS. The numbers of TPH-positive serotonergic and phosphorylated cyclic AMP response element binding protein (pCREB)-positive neurons and percentage of pCREB-positive serotonergic neurons in the DRN significantly increased after 3-h SCS. Further, the ipsilateral-to-contralateral immunoreactivity ratio of DβH increased in the LC of SNL rats and reached the level seen in naïve rats, even though the number of pCREB-positive neurons in the LC was unchanged by SNL and SCS. Moreover, 3-h SCS did not increase the expression levels of TPH and DβH in the spinal dorsal horn.

Conclusions

The serotonergic and noradrenergic pathways of the DAS are involved in the antinociceptive effect of SCS, but activation of the DRN might primarily be responsible for this effect, and the LC may have a smaller contribution. SCS does not potentiate the synthetic enzymes of 5HT and norepinephrine in the neuropathic spinal cord.

【 授权许可】

   
2015 Tazawa et al.

【 图 表 】

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