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

Background: Opioids such as morphine are used for treating moderate to severe pain. However, they also produce adverse effects such as nausea, constipation, addiction, and respiratory depression. Thus, other suitable analgesics need to be identified. Somatostatin is an inhibitory neuropeptide that modulates the transmission of pain. However, the half-life of somatostatin is short. In the present study, the antinociceptive effect of octreotide (a stable long-acting analog of somatostatin) was evaluated in rats with acute inflammatory pain. Methods: Sprague Dawley rats ( n = 42) were divided into control ( n = 6) and carrageenan injected groups ( n = 36). The carrageena group was divided into three equal subgroups and treated with saline, morphine (10 mg/kg), and octreotide (3 µg). Rats belonging to each subgroup ( n = 12) were again randomly divided into two equal sets. They were subjected to (a) behavioral evaluation of pain (allodynia) and estimation of paw edema, followed by immunohistochemical analysis of the expression of somatostatin type 2 receptor (sst2r) in the spinal cord and (b) estimation of open-field activity. Allodynia and paw edema were measured by von Frey filaments and plethysmometer, respectively, at 3 and 4 h after carrageenan injection. Expression of sst2r was examined after 24 hours, whereas open-field activity was evaluated after 3 hours. Results: In comparison to the saline-treated group, allodynia was partially attenuated by octreotide, though this was almost completely reversed by morphine. Paw edema was unaffected by octreotide, though it was marginally increased by morphine. This was not related to increased activity of rats, following relief from pain. Immunohistochemistry revealed a significant increase in the expression of sst2r in saline-treated rats, but a decrease in other groups. Conclusion: Octreotide has an antinociceptive effect, which was less than morphine. Increased edema following morphine could result from venodilation. Variations in the sst2r expression suggest its involvement in pain modulation at the spinal level. This information may have clinical relevance.

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“…An earlier study in our laboratory revealed that there is a turnover of the sst2A receptors at the spinal cord level following tissue injury. 13 …”

Section: Discussionmentioning

confidence: 99%

“…12 Similar to SST, octreotide has an antinociceptive effect in rats. 13,14 Besides, it also diminished hyperalgesia arising from antigen-induced arthritis. 15 Also, TT-232, another synthetic analog of SST, inhibited acute somatic and visceral nociception in rodents.…”

Section: Introductionmentioning

confidence: 93%

Comparison of Antinociceptive Effect of Octreotide With Morphine in a Rat Model of Acute Inflammatory Pain

Singh

Ray

2021

Annals of Neurosciences

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“…However, on the other hand, there was also conflicting evidence that SOM might contribute to nociception. Prasoon et al [86] observed an increased immunoreactivity of SOM in the lumbar spinal cord after post-incisional pain and suggested that SOM may contribute to post-incisional pain. SOM has a dual effect in spinal nociceptive processing dependent on various kinds of noxious stimuli.…”

Section: Discussionmentioning

confidence: 99%

Subclinical lipopolysaccharide from Salmonella Enteritidis induces neuropeptide dysregulation in the spinal cord and the dorsal root ganglia

Mikołajczyk

Złotkowska

2019

BMC Neurosci

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Background Despite increasing evidence that lipopolysaccharide (LPS) affects the biological active substances of dorsal root ganglia (DRG) we have limited knowledge of the influence of a single low dose of LPS, which does not result in any clinical symptoms of disease (subclinical LPS) on neuropeptides connected with the sensory pathway. Accordingly, in this work, we investigated the influence of subclinical LPS from Salmonella Enteritidis on selected neuropeptides: substance P (SP), galanin (GAL), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in the cervical, thoracic, lumbar and sacral regions of the DRG and spinal cord. Methods This study was performed on immature female pigs of the Pietrain × Duroc breed. Seven days after the intravenous injection of saline solution for control animals (n = 5) and 5 μg/kg b.w. LPS from S. Enteritidis for the experimental group (n = 5), the DRG and the spinal cord were collected to extract the neuropeptides using solid-phase extraction technology. Results Our results demonstrated that subclinical LPS in DRG was able to change the levels of all studied neuropeptides except SOM, whereas in the spinal cord it down-regulated all studied neuropeptides in the sacral spinal cord, maintaining the concentration of all studied neuropeptides in other regions similar to that observed in the control animals. The significant differences in the intensity and character of observed changes between particular regions of the DRG suggest that the exact functions of the studied neuropeptides and mechanisms of responses to subclinical LPS action depend on specific characteristics and functions of each examination region of DRG. Conclusions The mechanisms of observed changes are not fully understood and require further study of the molecular interactions between subclinical LPS from S . Enteritidis and neuronal and non-neuronal cells of DRG and spinal cord. The peripheral and central pain pathways must be analysed with the aspect of unknown long-term consequences of the influence of subclinical LPS from S. Enteritidis on neuropeptides in the spinal cord and the dorsal root ganglia.

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“…SST inhibits the release of several endocrine hormones such as growth hormone, prolactin, thyrotropin, gastrin, insulin, secretin, and glucagon [3,[5][6][7], and the local inflammatory reaction at the periphery [8,9]. As a neurotransmitter, SST plays role in many mechanisms centrally, such as pain transmission, mood coordination, and learning and behavioral responses to stress [3,[10][11][12][13]. It has emerging therapeutic relevance for the diagnosis and/or the treatment of numerous diseases, such as type 2 diabetes mellitus, Cushing disease, Alzheimer's disease, acromegaly, several neuroendocrine tumors, pain-associated conditions (inflammation, neuropathy, rheumatoid arthritis), and depression [6,[14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Exploration of Somatostatin Binding Mechanism to Somatostatin Receptor Subtype 4

Börzsei

Zsidó

Bálint

et al. 2022

IJMS

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Somatostatin (also named as growth hormone-inhibiting hormone or somatotropin release-inhibiting factor) is a regulatory peptide important for the proper functioning of the endocrine system, local inflammatory reactions, mood and motor coordination, and behavioral responses to stress. Somatostatin exerts its effects via binding to G-protein-coupled somatostatin receptors of which the fourth subtype (SSTR4) is a particularly important receptor mediating analgesic, anti-inflammatory, and anti-depressant effects without endocrine actions. Thus, SSTR4 agonists are promising drug candidates. Although the knowledge of the atomic resolution-binding modes of SST would be essential for drug development, experimental elucidation of the structures of SSTR4 and its complexes is still awaiting. In the present study, structures of the somatostatin–SSTR4 complex were produced using an unbiased, blind docking approach. Beyond the static structures, the binding mechanism of SST was also elucidated in the explicit water molecular dynamics (MD) calculations, and key binding modes (external, intermediate, and internal) were distinguished. The most important residues on both receptor and SST sides were identified. An energetic comparison of SST binding to SSTR4 and 2 offered a residue-level explanation of receptor subtype selectivity. The calculated structures show good agreement with available experimental results and indicate that somatostatin binding is realized via prerequisite binding modes and an induced fit mechanism. The identified binding modes and the corresponding key residues provide useful information for future drug design targeting SSTR4.

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

Cited by 12 publications

References 52 publications

Comparison of Antinociceptive Effect of Octreotide With Morphine in a Rat Model of Acute Inflammatory Pain

Comparison of Antinociceptive Effect of Octreotide With Morphine in a Rat Model of Acute Inflammatory Pain

Subclinical lipopolysaccharide from Salmonella Enteritidis induces neuropeptide dysregulation in the spinal cord and the dorsal root ganglia

Exploration of Somatostatin Binding Mechanism to Somatostatin Receptor Subtype 4

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