Somatostatin and its 2A Receptor in Dorsal Root Ganglia and Dorsal Horn of Mouse and Human: Expression, Trafficking and Possible Role in Pain

Abstract

BackgroundSomatostatin (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.ResultsSST 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 DRGsConclusionsThe 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.

Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer’s disease

“…Our previous results on dorsal root ganglia indicate that a SST-SSTR2a complex can be retrogradely transported [95], perhaps mediating intracellular, trophic effects in a similar way as nerve growth factor (NGF) [63]. Thus, one explanation might be that absence of SSTR2 prevents retrograde transport of SST required for proper maintenance and development of intact NA axons and nerve terminals.…”

Somatostatin-like immunoreactive primary sensory neurons supplying the porcine adrenal glands in physiological conditions and after adrenalectomy

“…Neurons in the DRG are bipolar cells, which have perikarya within ganglia and send their endings centrally to the dorsal horn of the spinal cord and peripherally to the skin and internal organs. Until now, both somatostatin and its receptors have been described in the DRG of various species, including humans (3,14,23). The presence of SOM has been mainly observed in small-cell-diameter neurons of the DRG, and prevalent types of somatostatin receptors in these ganglia are two variant forms of sst2 (sst2A and sst2B) (23).…”

Role of Somatostatin and Somatostatin Receptor type 2 in Postincisional Nociception in Rats

“…Somatostatin (SST) is a tetradecapeptide, which is widely expressed in the mammalian central and peripheral nervous systems (Carlton et al, 2004;Schindler et al, 1996;Schulz et al, 1998a;Shi et al, 2014). The corresponding high affinity somatostatin receptors are G proteincoupled receptors, which are divided into 5 subtypes (sstr1-5) (Lahlou et al, 2004).…”