Effects of the somatostatin analogue octreotide on rectal afferent nerves in humans

Plourde, Victor; Lembo, Tony; Shui, Zhikang; Parker, J.; Mertz, Howard; Taché, Yvette; Sytnik, B.; Mayer, Emeran A.

doi:10.1152/ajpgi.1993.265.4.g742

Cited by 62 publications

(74 citation statements)

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“…98 A schematic of receptor targets for SST receptor agonists is shown in Figure 2. In humans, octreotide, a non-selective SST2, SST3 and SST5 receptor agonist, has been demonstrated to have potent viscero analgesic, [99][100][101] as well as GI motility, effect. 102 Several pharmacodynamic studies have…”

Section: Somatostatin Receptor Agonistsmentioning

confidence: 99%

“…[99][100][101][103][104][105][106] Preliminary evidence from an 8-week controlled clinical treatment trial 107 showed that octreotide treatment was associated with a reduction in the perception of barostat-induced rectal distension in non-constipated IBS patients. In addition, octreotide treatment was found to reduce the abdominal complaints and improve the stool consistency, suggesting an overall beneficial effect.…”

Section: Somatostatin Receptor Agonistsmentioning

confidence: 99%

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Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease

Mayer¹,

Tillisch²,

Bradesi³

2006

Aliment Pharmacol Ther

119

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SummaryBackgroundThe importance of bi‐directional brain‐gut interactions in gastrointestinal illness is increasingly being recognized, most prominently in the area of functional gastrointestinal disorders. Numerous current and emerging therapies aimed at normalizing brain–gut interactions are a focus of interest, particularly for irritable bowel syndrome and functional dyspepsia.MethodsA literature search was completed for preclinical and clinical studies related to central modulation of gastrointestinal functions and published in English between 1980 and 2006.ResultsExisting data, while sparse, support the use of different classes of antidepressant drugs, including tricyclics, and selective and non‐selective serotonin reuptake inhibitors in irritable bowel syndrome. Serotonin receptor agonists and antagonists with peripheral and possibly central effects are effective in treating specific subtypes of irritable bowel syndrome. Based largely on theoretical and preclinical evidence, several novel compounds that selectively target receptors at multiple levels within the brain–gut axis such as neurokinin, somatostatin and corticotropin‐releasing factor receptor antagonists are promising.ConclusionsThis review discusses the rationale for modulation of the brain–gut axis in the treatment of functional gastrointestinal disorders and highlights the most promising current and future therapeutic strategies.

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Section: Somatostatin Receptor Agonistsmentioning

confidence: 99%

Section: Somatostatin Receptor Agonistsmentioning

confidence: 99%

Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease

Mayer¹,

Tillisch²,

Bradesi³

2006

Aliment Pharmacol Ther

119

View full text Add to dashboard Cite

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“…First, SRIF is localized in a subset of small-diameter dorsal root ganglion (DRG) cells (Hökfelt et al, 1975). Second, activation of SRIF receptors results in inhibition of both nociceptive behaviors in animals (Eschalier et al, 1991;Chapman and Dickenson, 1992;Corsi et al, 1997;Carlton et al, 2001) (but see Hitosugi et al, 1999;Kamei et al, 1999) and acute and chronic pain in humans Meynadier et al, 1985;Plourde et al, 1993;Taura et al, 1994;Paice et al, 1996). Third, SRIF inhibits dorsal horn neuronal activity (Randic and Miletic, 1978;Miletic and Randic, 1982;Murase et al, 1982;Sandkuhler et al, 1990).…”

Section: Abstract: Primary Afferent; Nociception; Inhibitory Peptidementioning

confidence: 99%

Tonic Control of Peripheral Cutaneous Nociceptors by Somatostatin Receptors

Carlton

Zhou

et al. 2001

J. Neurosci.

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The peptide somatostatin [somatotropin release-inhibiting factor (SRIF)] is widely distributed in the body and exerts a variety of hormonal and neural actions. Several lines of evidence indicate that SRIF is important in nociceptive processing: (1) it is localized in a subset of small-diameter dorsal root ganglion cells; (2) activation of SRIF receptors results in inhibition of both nociceptive behaviors in animals and acute and chronic pain in humans; (3) SRIF inhibits dorsal horn neuronal activity; and (4) SRIF reduces responses of joint mechanoreceptors to noxious rotation of the knee joint. The goal of the present study is to show that cutaneous nociceptors are under the tonic inhibitory control of SRIF. This is accomplished using behavioral and electrophysiological paradigms. In a dose-dependent manner, intraplantar injection of the SRIF receptor antagonist cyclosomatostatin (c-SOM) results in nociceptive behaviors in normal animals and enhancement of nociceptive behaviors in formalin-injected animals, and these actions can be blocked when c-SOM is coapplied with three different SRIF agonists. Furthermore, intraplantar injection of SRIF antiserum also results in nociceptive behaviors. Electrophysiological recordings using an in vitro glabrous skin-nerve preparation show increased nociceptor activity in response to c-SOM, and this increase is blocked by the same three SRIF agonists. Parallel behavioral and electrophysiological studies using the opioid antagonist naloxone demonstrate that endogenous opioids do not maintain a tonic inhibitory control over peripheral nociceptors, nor does opioid receptor antagonism influence peripheral SRIF effects on nociceptors. These findings demonstrate that SRIF receptors maintain a tonic inhibitory control over peripheral nociceptors, and this may contribute to mechanisms that control the excitability of these terminals.

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“…Although central processes contribute to colorectal hypersensitivity, the driving force is increased afferent mechanosensitivity (i.e., sensitization). For example, intrarectal lidocaine reduces pain evoked by rectal distension in healthy subjects as well as ongoing pain and both visceral and somatic (referred) hypersensitivity in patients with IBS (24,32,49,50). Accordingly, reversing or moderating afferent sensitization and hyperexcitability is a clinically important goal, and developing drugs that selectively target colorectal mechanosensation and/or sensitization would improve management of IBS pain.…”

mentioning

confidence: 99%

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

Kiyatkin

Feng

Schwartz

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Kiyatkin ME, Feng B, Schwartz ES, Gebhart GF. Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization. Am J Physiol Gastrointest Liver Physiol 305: G638 -G648, 2013. First published August 29, 2013; doi:10.1152/ajpgi.00180.2013.-The ligand-gated channels transient receptor potential vanilloid 1 (TRPV1) and P2X3 have been reported to facilitate colorectal afferent neuron sensitization, thus contributing to organ hypersensitivity and pain. In the present study, we hypothesized that TRPV1 and P2X3 cooperate to modulate colorectal nociception and afferent sensitivity. To test this hypothesis, we employed TRPV1-P2X3 double knockout (TPDKO) mice and channel-selective pharmacological antagonists and evaluated combined channel contributions to behavioral responses to colorectal distension (CRD) and afferent fiber responses to colorectal stretch. Baseline responses to CRD were unexpectedly greater in TPDKO compared with control mice, but zymosan-produced CRD hypersensitivity was absent in TPDKO mice. Relative to control mice, proportions of mechanosensitive and -insensitive pelvic nerve afferent classes were not different in TPDKO mice. Responses of mucosal and serosal class afferents to mechanical probing were unaffected, whereas responses of muscular (but not muscular/mucosal) afferents to stretch were significantly attenuated in TPDKO mice; sensitization of both muscular and muscular/mucosal afferents by inflammatory soup was also significantly attenuated. In pharmacological studies, the TRPV1 antagonist A889425 and P2X3 antagonist TNP-ATP, alone and in combination, applied onto stretch-sensitive afferent endings attenuated responses to stretch; combined antagonism produced greater attenuation. In the aggregate, these observations suggest that 1) genetic manipulation of TRPV1 and P2X3 leads to reduction in colorectal mechanosensation peripherally and compensatory changes and/or disinhibition of other channels centrally, 2) combined pharmacological antagonism produces more robust attenuation of mechanosensation peripherally than does antagonism of either channel alone, and 3) the relative importance of these channels appears to be enhanced in colorectal hypersensitivity. pelvic nerve; purinergic receptor; single fiber; transient receptor potential; visceral pain CHRONIC ABDOMINAL PAIN is a key feature of irritable bowel syndrome (IBS), which is prevalent, costly, and difficult to manage. An important contributor to pain in IBS is heightened perception of mechanical events in the bowel (i.e., hypersensitivity). Indeed, patients with IBS typically report greater pain and/or reduced response thresholds to rectal balloon distension than control subjects (3,24,28,34,46). Although central processes contribute to colorectal hypersensitivity, the driving force is increased afferent mechanosensitivity (i.e., sensitization). For example, intrarectal lidocaine reduces pain evoked by rectal distension in healthy subjects as well as ongoing pain and both vi...

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Effects of the somatostatin analogue octreotide on rectal afferent nerves in humans

Cited by 62 publications

References 0 publications

Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease

Review article: modulation of the brain–gut axis as a therapeutic approach in gastrointestinal disease

Tonic Control of Peripheral Cutaneous Nociceptors by Somatostatin Receptors

Combined genetic and pharmacological inhibition of TRPV1 and P2X3 attenuates colorectal hypersensitivity and afferent sensitization

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