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Involvement of Spinal Somatostatin Receptor SST2A in Inflammation-Induced Thermal Hyperalgesia: Ultrastructural and Behavioral Studies in Rats

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Abstract

Our previous results have shown that somatostatin receptor subtype SST2A is responsible for thermal, but not mechanical nociceptive transmission in the rat spinal cord. The present study was undertaken to further examine the ultrastructural localization of SST2A receptor in lamina II of the spinal dorsal horn and the role of SST2A receptor in thermal hyperalgesia following Complete Freund’s Adjuvant (CFA)-induced inflammation. We found that SST2A receptors in lamina II are located primarily in postsynaptic dendrites and soma, but not in axons or synaptic terminals. CFA-induced inflammation markedly increased SST2A receptor-like immunoreactivity in lamina II. Paw withdrawal latency (PWL) evoked by noxious heating was obviously shortened 1 h after intraplantar injection of CFA, exhibiting thermal hyperalgesia. Pre-blocking SST2A activity by intrathecal pre-administration of CYN154806, a broad-spectrum antagonist of SST2 receptor, or specific antiserum against SST2A receptor (anti-SST2A) significantly attenuated thermal hyperalgesia in a dose-dependent fashion in CFA-treated rats. But, administration of anti-SST2A or CYN154806 after CFA treatment had no effect upon thermal hyperalgesia. Intrathecal application of SST2A agonist SOM-14 at different doses prior to CFA treatment did not influence thermal hyperalgesia in inflamed rats, but at a low dose shortened PWL evoked by noxious heating in normal rats. These results suggest that spinal SST2A receptors play a key role in triggering the generation, but not maintenance, of thermal hyperalgesia evoked by CFA-induced inflammation. The up-regulation of SST2A receptors in the spinal cord may be one of the mechanisms underlying inflammation-induced thermal hyperalgesia.

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Abbreviations

ANOVA:

Analysis of variance

anti-SST2A :

Antiserum against SST2A receptor

CFA:

Complete Freunds’s Adjuvant

DAB:

3,3-diaminobenzidine

i.t.:

Intrathecal

NGST:

Normal goat serum in PBS with Triton X-100

PB:

Phosphate buffer

PBS:

Phosphate buffered saline

PWL:

Paw withdrawal latency

SOM:

Somatostatin

SOM-LI:

SOM-like immunoreactive

SST:

Somatostatin receptor

SST2A-LI:

SST2A receptors-like immunoreactivity

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Acknowledgments

We are grateful to Prof. S. Schulz for the gift of antiserum against SST2A receptor. The work was supported by grants from National Basic Research Program of China Grant (No. 2006CB500807 and 2007CB5125) for Z. Q. Zhao, Postdoctoral Science Foundation of China (1999) and Chinese Academy of Sciences KC Wong Postdoctoral Research Award Fund (2000-the 21st) for Dr. J. Y. Hu.

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Author notes

  1. Jiang-Yuan Hu

    Present address: Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

Authors and Affiliations

  1. Institute of Neurobiology, Institutes of Brain Science, Fu-Dan University, 138 Yixueyan Road, Shanghai, 200032, People’s Republic of China

    Jun Zhao, Jiang-Yuan Hu, Yu-Qiu Zhang & Zhi-Qi Zhao

  2. State Key Laboratory of Medical Neurobiology, Fu-Dan University, 138 Yixueyan Road, Shanghai, 200032, People’s Republic of China

    Jun Zhao, Jiang-Yuan Hu, Yu-Qiu Zhang & Zhi-Qi Zhao

  3. Institute of Neurobiology, Fu-Dan University, 138 Yixueyan Road, Shanghai, 200032, People’s Republic of China

    Zhi-Qi Zhao

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  1. Jun Zhao
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Correspondence to Zhi-Qi Zhao.

Additional information

Special issue article in honor of Dr. Ji-Sheng Han.

Jun Zhao and Jiang-Yuan Hu—contributed equally in this paper.

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Zhao, J., Hu, JY., Zhang, YQ. et al. Involvement of Spinal Somatostatin Receptor SST2A in Inflammation-Induced Thermal Hyperalgesia: Ultrastructural and Behavioral Studies in Rats. Neurochem Res 33, 2099–2106 (2008). https://doi.org/10.1007/s11064-008-9713-x

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