Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery

Dahaba, Ashraf A.; Mueller, Gabriele; Mattiassich, Georg; Rumpold-Seitlinger, Gudrun; Bornemann, Helmar; Rehak, Peter; Linck, Guillermo; Mischinger, H. J.; Metzler, H.

doi:10.1016/j.ejpain.2008.10.006

Cited by 20 publications

(9 citation statements)

References 15 publications

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“…Similarly, administration of TT232, a somatostatin analog acting through peripheral SST4 receptors was devoid of significant toxicity or side effects in humans (Szolcsányi et al, 2004 ; Szokolóczi et al, 2005 ). Octreotide can alleviate pain behavior in patients (Penn et al, 1992 ; Dahaba et al, 2009 ). However, given its in vitro selectivity profile, octreotide's analgesic effect is most likely independent of SST4 receptor and more related to activation of SST2 receptor (Imhof et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

et al. 2018

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In the majority of patients with breast cancer in the advanced stages, skeletal metastases are common, which may cause excruciating pain. Currently available drug treatments for relief of breast cancer-induced bone pain (BCIBP) include non-steroidal anti-inflammatory drugs and strong opioid analgesics along with inhibitors of osteoclast activity such as bisphosphonates and monoclonal antibodies such as denosumab. However, these medications often lack efficacy and/or they may produce serious dose-limiting side effects. In the present study, we show that J-2156, a somatostatin receptor type 4 (SST4 receptor) selective agonist, reverses pain-like behaviors in a rat model of BCIBP induced by unilateral intra-tibial injection of Walker 256 breast cancer cells. Following intraperitoneal administration, the ED50 of J-2156 for the relief of mechanical allodynia and mechanical hyperalgesia in the ipsilateral hindpaws was 3.7 and 8.0 mg/kg, respectively. Importantly, the vast majority of somatosensory neurons in the dorsal root ganglia including small diameter C-fibers and medium-large diameter fibers, that play a crucial role in cancer pain hypersensitivities, expressed the SST4 receptor. J-2156 mediated pain relief in BCIBP-rats was confirmed by observations of a reduction in the levels of phosphorylated extracellular signal-regulated kinase (pERK), a protein essential for central sensitization and persistent pain, in the spinal dorsal horn. Our results demonstrate the potential of the SST4 receptor as a pharmacological target for relief of BCIBP and we anticipate the present work to be a starting point for further mechanism-based studies.

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Section: Discussionmentioning

confidence: 99%

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

et al. 2018

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“…It could be possible that ODT8-SST-activated oxytocin neurons play a role to counteract some stressful behavior, such as scratching since oxytocin has anxiolytic effect (Blume et al, 2008). However, it cannot be excluded that oxytocin and vasopressin are involved in other central actions of somatostatin (Legros, 2001) including analgesia (Dahaba et al, 2009) as recent evidence showed that oxytocin-induced analgesia is mediated by the vasopressin-1A receptor (Schorscher-Petcu et al, 2010). …”

Section: Discussionmentioning

confidence: 99%

Pattern of Fos expression in the brain induced by selective activation of somatostatin receptor 2 in rats

et al. 2010

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Central activation of somatostatin (sst) receptors by oligosomatostatin analogs inhibits growth hormone and stress-related rise in catecholamine plasma levels while stimulating grooming, feeding behaviors, gastric transit and acid secretion, which can be mimicked by selective sst2 receptor agonist. To evaluate the pattern of neuronal activation induced by peptide sst receptor agonists, we assessed Fos-expression in rat brain after intracerebroventricular (icv) injection of a newly developed selective sst2 agonist compared to the oligosomatostatin agonist, ODT8-SST, a pan-sst1–5 agonist. Ninety min after injection of vehicle (10µl) or previously established maximal orexigenic dose of peptides (1µg=1nmol/rat), brains were assessed for Fos-immunohistochemistry and doublelabeling. Food and water were removed after injection. The sst2 agonist and ODT8-SST induced a similar Fos distribution pattern except in the arcuate nucleus where only the sst2 agonist increased Fos. Compared to ODT8-SST, the sst2 agonist induced higher Fos-expression by 3.7-fold in the basolateral amygdaloid nucleus, 1.2-fold in the supraoptic nucleus (SON), 1.6-fold in the magnocellular paraventricular hypothalamic nucleus (mPVN), 4.1-fold in the external lateral parabrachial nucleus, and 2.6-fold in both the inferior olivary nucleus and superficial layer of the caudal spinal trigeminal nucleus. Doublelabeling in the hypothalamus showed that ODT8-SST activates 36% of oxytocin, 63% of vasopressin and 79% of sst2 immunoreactive neurons in the mPVN and 28%, 55% and 25% in the SON, respectively. Selective activation of sst2 receptor results in a more robust neuronal activation than the pan-sst1–5 agonist in various brain regions that may have relevance in sst2 mediated alterations of behavioral, autonomic and endocrine functions.

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“…These latter have been cloned and characterized, eventually leading to the discovery of five different molecules (referred to as SSTR1‐5) that have been collected into two main families on the basis of structural and functional features (Viollet et al, 1995; Patel, 1999). The effects of SST in spinal cord are usually associated with an inhibition of nociceptive neurotransmission in several experimental paradigms (Carlton et al, 2001; Su et al, 2001; Malcangio et al, 2002), and the peptide, as well as its synthetic analogue octreotide (OCT), have been shown to evoke analgesia in many clinical situations, including several different types of pathological pain (Penn et al, 1992; Paice et al, 1996; Dahaba et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The somatostatin analogue octreotide inhibits capsaicin‐mediated activation of nociceptive primary afferent fibres in spinal cord lamina II (substantia gelatinosa)

Bencivinni

Ferrini

Salio

et al. 2011

European Journal of Pain

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Somatostatin (SST) in spinal cord has been linked with the inhibition of nociceptive neurotransmission in several experimental paradigms. The SST2 receptor (SSTR2) is the main SST receptor subtype in the superficial dorsal horn (DH) and is activated, besides to the naïve peptide, by the SST synthetic analogue octreotide (OCT). In the present work, we have studied the central effects of SSTR2 activation on capsaicin (CAP)-induced glutamate release in mouse DH. In neurons of the lamina II of DH, CAP (2 μM) induced a strong increase of mEPSC frequency that was significantly reduced (70%) by OCT. SSTR2 involvement was assessed by using the specific antagonist CYN 154806. No differences were observed between frequency increase in CAP alone vs. CAP in the presence of CYN 154806+OCT. The effect of OCT was further investigated by studying c-fos expression in spinal cord slices. The CAP-induced increase in density of Fos immunoreactive nuclei in the superficial DH was strongly prevented by OCT. SSTR2a (a splicing variant of SSTR2) immunoreactivity was found in both pre- and post-synaptic compartments of laminae I-II synapses. By light and electron microscopy, SSTR2a was mainly localized onto non-peptidergic isolectin B4 (IB4)-positive primary afferent fibres (PAFs). A subset of them was also found to express the CAP receptor TRPV1. These data show that the SST analogue OCT inhibits CAP-mediated activation of non-peptidergic nociceptive PAFs in lamina II. Our data indicate that SSTR2a plays an important role in the pre-synaptic modulation of central excitatory nociceptive transmission in mouse.

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Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery

Cited by 20 publications

References 15 publications

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

Pattern of Fos expression in the brain induced by selective activation of somatostatin receptor 2 in rats

The somatostatin analogue octreotide inhibits capsaicin‐mediated activation of nociceptive primary afferent fibres in spinal cord lamina II (substantia gelatinosa)

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