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Somatostatin and its 2A receptor in dorsal root ganglia and dorsal horn of mouse and human: expression, trafficking and possible role in pain

Tie-Jun Sten Shi123*, Qiong Xiang12, Ming-Dong Zhang14, Swapnali Barde1, Ylva Kai-Larsen14, Kaj Fried1, Anna Josephson1, Laura Glück5, Sergey M Deyev6, Andrei V Zvyagin7, Stefan Schulz5 and Tomas Hökfelt1

Author Affiliations

1 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

2 School of Life Science and Technology, Harbin Institute of Technology, Harbin, China

3 Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden

4 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17177, Sweden

5 Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University, Jena, Germany

6 Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia

7 MQ Biofocus Research Centre, Macquarie University, Sydney, NSW, Australia

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Molecular Pain 2014, 10:12  doi:10.1186/1744-8069-10-12

Published: 13 February 2014

Abstract

Background

Somatostatin (SST) and some of its receptor subtypes have been implicated in pain signaling at the spinal level. In this study we have investigated the role of SST and its sst2A receptor (sst2A) in dorsal root ganglia (DRGs) and spinal cord.

Results

SST and sst2A protein and sst2 transcript were found in both mouse and human DRGs, sst2A-immunoreactive (IR) cell bodies and processes in lamina II in mouse and human spinal dorsal horn, and sst2A-IR nerve terminals in mouse skin. The receptor protein was associated with the cell membrane. Following peripheral nerve injury sst2A-like immunoreactivity (LI) was decreased, and SST-LI increased in DRGs. sst2A-LI accumulated on the proximal and, more strongly, on the distal side of a sciatic nerve ligation. Fluorescence-labeled SST administered to a hind paw was internalized and retrogradely transported, indicating that a SST-sst2A complex may represent a retrograde signal. Internalization of sst2A was seen in DRG neurons after systemic treatment with the sst2 agonist octreotide (Oct), and in dorsal horn and DRG neurons after intrathecal administration. Some DRG neurons co-expressed sst2A and the neuropeptide Y Y1 receptor on the cell membrane, and systemic Oct caused co-internalization, hypothetically a sign of receptor heterodimerization. Oct treatment attenuated the reduction of pain threshold in a neuropathic pain model, in parallel suppressing the activation of p38 MAPK in the DRGs

Conclusions

The findings highlight a significant and complex role of the SST system in pain signaling. The fact that the sst2A system is found also in human DRGs and spinal cord, suggests that sst2A may represent a potential pharmacologic target for treatment of neuropathic pain.

Keywords:
Axonal transport; Nerve injury; Neuropeptide; NPY receptor; Receptor internalization; Retrograde signaling