Somatostatin analogue treatment attenuates histological findings of inflammation and increases mRNA expression of interleukin-1 beta in the articular tissues of rats with ongoing adjuvant-induced arthritis

Paran, Daphna; Kidron, Devora; Mayo, Ami; Ziv, Ofer; Chowers, Yehuda; Caspi, Dan; Yaron, Michael; Paran, Haim

doi:10.1007/s00296-004-0455-z

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…Thus, the present study indicates that local antinociceptive effects of octreotide occurred through the activation of peripheral somatostatin receptors, most likely by SSTR2. The results are also consistent with previous studies demonstrating that somatostatin has analgesic effects in rodents and humans by acting on peripheral somatostatin receptors [5, 43, 44]. It is reported that SSTR2 inhibits activity through the presynaptic release of glutamate evoked by TRPV1 in the spinal cord [3].…”

Section: Discussionsupporting

confidence: 92%

The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

Luo

Guo

et al. 2014

BioMed Research International

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The present study examined nociceptive behaviors and the expression of phosphorylated cAMP response element-binding protein (pCREB) in the dorsal horn of the lumbar spinal cord and the dorsal root ganglion (DRG) evoked by bee venom (BV). The effect of intraplantar preapplication of the somatostatin analog octreotide on nociceptive behaviors and pCREB expression was also examined. Subcutaneous injection of BV into the rat unilateral hindpaw pad induced significant spontaneous nociceptive behaviors, primary mechanical allodynia, primary thermal hyperalgesia, and mirror-thermal hyperalgesia, as well as an increase in pCREB expression in the lumbar spinal dorsal horn and DRG. Octreotide pretreatment significantly attenuated the BV-induced lifting/licking response and mechanical allodynia. Local injection of octreotide also significantly reduced pCREB expression in the lumbar spinal dorsal horn and DRG. Furthermore, pretreatment with cyclosomatostatin, a somatostatin receptor antagonist, reversed the octreotide-induced inhibition of the lifting/licking response, mechanical allodynia, and the expression of pCREB. These results suggest that BV can induce nociceptive responses and somatostatin receptors are involved in mediating the antinociception, which provides new evidence for peripheral analgesic action of somatostatin in an inflammatory pain state.

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Section: Discussionsupporting

confidence: 92%

The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

Luo

Guo

et al. 2014

BioMed Research International

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“…In other models of inflammation SST has been shown to inhibit IL-6 and IL-8 mRNA expression as well as the protein synthesis of these pro-inflammatory cytokines. 28,29 The lack of an anti-inflammatory effect in the present study, as reflected by the cytokines analysis may due to inadequate dosing and/or inappropriate timing of SST administration during the evolution of the disease. The beneficial effect on weight gain seen in the treated animals may reflect a general 'well-being effect' related to a better protein balance, but also a possible systemic neuroendocrine effect via suppression of prolactin and GH secretion.…”

Section: Discussionmentioning

confidence: 89%

Somatostatin Treatment Attenuates Proteinuria and Prevents Weight Loss in NZB/W F1 Mice

Paran

Bernheim²,

Golan

et al. 2006

Lupus

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Somatostatin, a naturally occurring neuropeptide, is an immunomodulator which inhibits humoral and cell mediated immunity as well as secretion of proinflammatory cytokines. The objective of this study was to examine the effects of a somatostatin analogue on the severity of glomerulonephritis in the female NZB/W F1 murine model of systemic lupus erythematosus (SLE). Twenty female NZB/W F1 mice were treated at 23 weeks of age with 10 mg/kg of the somatostatin analogue Sandostatin- LAR, IM every four weeks. Ten control mice received IM injection of vehicle. Mice were assessed at four-week intervals for weight change, proteinuria, anti-DNA antibodies and splenocyte cytokine profile. The mice were sacrificed at age 34.5 weeks. Kidneys were collected and evaluated by light and immunofluorescence (IF) microscopy. Spleens were collected and splenocyte intracellular cytokines were measured by FACS analysis. In the treatment group significantly less proteinuria was observed four weeks after the second somatostatin analogue injection (dipstik scale: +2.07 +/- 0.95 versus. +3.5 +/- 1.08, P = 0.0002). The treated mice did not lose weight while the control group lost weight over time (P = 0.016). No differences were noted between the groups in anti-DNA antibody titres, cytokine profile or the severity of lupus nephritis as assessed by light and IF microscopy. Somatostatin analogue treatment attenuated proteinuria and prevented weight loss in NZB/W F1 mice, suggesting a possible beneficial effect on renal parameters and systemic manifestations of the disease. Further studies will be needed to assess the value of somatostatin analogue treatment in lupus nephritis, utilizing higher doses, at different stages of the disease, for longer periods.

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“…We have chosen to evaluate the SSTR2a central response to OCT in a slice inflammatory pain model since numerous preclinical and clinical studies have implicated SSTR2 in the response to peripheral inflammation (see for example Ji et al, 2006; Paran et al, 2001, 2005), and SST is widely recognized as an endogenous anti‐inflammatory peptide (see Malcangio, 2003). Nonetheless, SST has been also linked to the onset of neuropathic pain (Dong et al, 2006; Adler et al, 2009), mainly in response to glial cell‐line derived neurotrophic factor (GDNF) stimulation.…”

Section: Discussionmentioning

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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Somatostatin analogue treatment attenuates histological findings of inflammation and increases mRNA expression of interleukin-1 beta in the articular tissues of rats with ongoing adjuvant-induced arthritis

Abstract: Treatment with a somostatin analogue attenuated early inflammatory changes in AIA joints and increased mRNA expression of IL-1beta in the articular tissues of rats with ongoing arthritis. Improvement in the physical findings of joint inflammation was mild.

Cited by 9 publications

References 28 publications

The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

The Inhibitory Effect of Somatostatin Receptor Activation on Bee Venom-Evoked Nociceptive Behavior and pCREB Expression in Rats

Somatostatin Treatment Attenuates Proteinuria and Prevents Weight Loss in NZB/W F1 Mice

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

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