title: Somatostatin and its 2A receptor in dorsal root ganglia and dorsal horn of mouse and human: expression, trafficking and possible role in pain.
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.
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Tiejun.Shi@ki.se.
authors: Tie-Jun Sten
authors: TJ
authors: Shi
authors: Qiong
authors: Q
authors: Xiang
authors: Ming-Dong
authors: MD
authors: Zhang
authors: Swapnali
authors: S
authors: Barde
authors: Ylva
authors: Y
authors: Kai-Larsen
authors: Kaj
authors: K
authors: Fried
authors: Anna
authors: A
authors: Josephson
authors: Laura
authors: L
authors: Glück
authors: Sergey M
authors: SM
authors: Deyev
authors: Andrei V
authors: AV
authors: Zvyagin
authors: Stefan
authors: S
authors: Schulz
authors: Tomas
authors: T
authors: Hökfelt
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D005727:Ganglia, Spinal / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000172:deficiency / Q000235:genetics; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D009842:Oligopeptides / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012585:Sciatica / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: C403089:CYN 154806; D009842:Oligopeptides; D017481:Receptors, Somatostatin; C570769:somatostatin receptor 2, mouse; D049452:Green Fluorescent Proteins; D013004:Somatostatin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D015282:Octreotide