Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide is a synthetic somatostatin analogue that has been recently tested by various routes of administration as an analgesic drug for different types of pain. The authors evaluated the analgesic efficacy of a subcutaneous 200-ng bolus of octreotide on somatic and visceral pain from advanced cancer in a randomized, single-blind crossover study. The results in nine cases did not show an analgesic effect superior to that of a placebo. Pain relief was obtained in one case of postprandial visceral pain. This case is discussed in detail, and another possible clinical use for octreotide in a particular form of neoplastic pain is hypothesized.
J Pain Symptom Manage 1994 Jan
PMID:Subcutaneous octreotide in the treatment of pain in advanced cancer patients. 816 58

Somatostatin (Som) administered intrathecally to humans has been shown to exert potent analgesic effects on somatic pain, and anecdotal evidence suggests that Som may also relieve visceral pain. In the current study, we used rectal balloon distension in seven healthy volunteers to evaluate the effect of the Som analogue octreotide (Oct; 1.25 microgram/kg sc) on four pathways mediated by different visceral afferents that originate in the rectum: conscious perception, receptive relaxation, reflex inhibition of internal anal sphincter, and a viscerosomatic reflex. Rectal mechanoreceptors were stimulated either by distending the rectum tonically (volume ramp at 20-40 and 400 ml/min) or phasically (intermittent pressure steps of 60 s duration). Pressure thresholds for nonnoxious and noxious sensations in response to slow tonic distension were increased in the presence of rectal lidocaine (20 ml of 2% solution), whereas those to phasic distension were unaffected. Oct significantly increased pressure and volume thresholds for nonnoxious and noxious sensations in response to slow tonic distension but did not further increase thresholds in the presence of intrarectal lidocaine. In contrast, no effect of Oct on rectal sensations was observed during rapid tonic or phasic distension. Oct had no effect on any of the monitored reflex responses. The effect of Oct on rectal sensation in the concentration used in this study was not associated with changes in the rectal wall pressure-volume relationship during any distension protocol. These findings indicate that the inhibitory effect of Oct on rectal sensation is likely to represent a direct effect on a subset of extrinsic primary afferent neurons, with receptive fields in the mucosa.
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PMID:Effects of the somatostatin analogue octreotide on rectal afferent nerves in humans. 823 58

Amongst the spinal peptide candidates believed to be involved in the mediation of analgesia, only somatostatin fulfills the criterium of a real analgesia substance. Spinal somatostatin specifically blocks the transmission of painful stimuli. Spinal calcitonin may lower the opioid dose requirement in patients with bone metastases but it fails to relieve acute pain. The usefulness of ACTH and CRF for treatment of pain remains to be established. The role of CCK-8, vasopressin and neurotensin is unclear. The contradictory findings on antinociception using simple rodent withdrawal reflex tests (e.g. the tail flick test), or more complex behavioral tests in which supraspinal sensory processing is involved, (e.g. the hot plate test), indicate that these tests are inappropriate when neuropeptides are employed. Furthermore, due to their inability to predict analgesia in humans, they do not fulfill the guidelines proposed by the IASP that animal test procedures have to be for the benefit of humans.
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PMID:Non-opioid peptides for analgesia. 831 62

Two acromegalic patients with severe headache were treated with the somatostatin analogue, octreotide (Sandostatin). A double-blind study of octreotide versus placebo in which pain intensity was measured using a visual analogue scale (VAS) was performed initially with these patients. A rapid (within 4-15 min) pain relief occurred lasting 2-8.5 h after injection of 100 micrograms of octreotide, an effect that was not reversed by intravenous (i.v.) naloxone. These 2 acromegalic patients then received treatment for 71 and 82 months, respectively, with doses starting at 500 micrograms/day and 1500 micrograms/day, respectively, without evidence of either tolerance or dependence, although the effect of octreotide on headache appears to be selective. No unwanted sedative effect has been observed. A screening procedure with injection of 50 micrograms of subcutaneous (s.c.) octreotide was performed in 11 other patients with chronic severe pain associated with various conditions. Only 3 patients (2 with diabetic polyneuropathy and 1 with bone pain associated with myelodysplastic syndrome) reported more than 50% pain relief. In the insulin-dependent diabetic patients the double-blind check was not performed due to the risk of octreotide-induced hypoglycemia. In the patient with bone pain the same double-blind check as in the acromegalic patients could not confirm the analgesic effect. It may thus be concluded that octreotide appears to be useful for the treatment of both chronic and acute severe painful conditions in acromegalic patients. However, since its analgesic effect in our patients was confined to headaches only, further controlled studies must be carried out in order to determine appropriate target groups.
Pain 1993 May
PMID:Analgesic effect of the somatostatin analogue octreotide in two acromegalic patients: a double-blind study with long-term follow-up. 833 92

The cerebrospinal fluid (CSF) levels of the opioid peptides met-enkephalin (ME), beta-endorphin (BE) and dynorphin (DYN) as well as the putative sensory neuropeptides substance P (SP), somatostatin (SOM), calcitonin gene related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were determined in 10 patients with severe nociceptive pain due to malignancy, before and after initiation of spinal opioid therapy, and in 10 control patients. Pain intensity, evaluated by means of a 100-mm visual analog scale (VAS), was reduced from 39 +/- 9 to 18 +/- 10 for continuous pain and from 70 +/- 10 to 10 +/- 8 for intermittent pain (means +/- s.e.mean). Lumbar CSF immunoreactive ME and DYN concentrations were significantly increased (P = 0.05) and BE and VIP were significantly decreased (P < or = 0.05) in the pain patients. A slight, but non-significant (P = 0.06) decrease in SP-like immunoreactivity was found after initiation of spinal opioid therapy. Visceral pain seemed to be associated with low immunoreactive SP and ME concentrations compared to somatic pain. A highly significant correlation was found between SP and ME (P < 0.001) and to a lesser extent also between other peptides. We conclude that the concentrations of the endogenous opioids were more affected by nociceptive pain states than the non-opioid peptides. The origin of pain may also influence the results. The postulated inhibition of peptide release by spinal opioid application seemed to be present for SP, but could otherwise not be confirmed.
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PMID:CSF neuropeptides in cancer pain: effects of spinal opioid therapy. 835 65

Dorsal root ganglia (DRG) neuronopathy was induced in rats by chronic treatment (2 mg/kg twice a week for nine injections) with the antineoplastic drug cisplatin. Morphological alterations and changes in peptide [calcitonin gene-related peptide (CGRP), substance P, galanin (Gal), and somatostatin] concentration were studied in the DRG, the spinal cord, and the sciatic nerve. Peptide concentration was increased in DRG neurons, with CGRP and Gal showing the highest increase. Conversely, in the sciatic nerve there was a general decrease in peptide content. In DRG a reduction in the nuclear, cytoplasmic, and nucleolar areas of primary sensory neurons was evident and was accompanied by clear-cut aspects of nucleolar structural damage. In peripheral nerves only extensive morphometric determinations could evidence a reduction in nerve conduction velocities and impairment in pain detection and coordination. Some of the nerve fibers presented axonal and adaxonal accumulations, suggesting the presence of an axonopathy. These results confirm that DRG cells are the primary target of cisplatin-induced neurotoxicity. Milder alterations can be detected in peripheral nerves. The increase in peptide concentration in DRG is probably due to cisplatin-related damage to the axonal transport system rather than to an increased synthesis.
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PMID:Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy. 859

Somatostatin is distributed in the substantia gelatinosa in the dorsal horn of the spinal cord, and its application has been found to produce an inhibitory effect on nociceptive neurons. Although intraspinal administration of somatostatin-14 produces pain relief in patients with cancer and in postoperative patients, its short half-life limits its clinical usefulness. Octreotide, a synthetic analog of somatostatin, is more stable and not been associated with neurodegenerative changes when administered intrathecally in dogs. Intrathecal octreotide provides analgesia without adverse drug effects when administered chronically for cancer pain; however, treatment periods have been limited. This article describes the 5-year clinical course of two patients receiving intrathecal octreotide for severe, intractable nonmalignant pain. Included in this description are the results of blinded, randomized "N of 1" trials conducted in each of these patients.
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PMID:Intrathecal octreotide for relief of intractable nonmalignant pain: 5-year experience with two cases. 874 73

The purpose of this study was to verify the role of somatostatin (Som) of brain in analgesia of electroacupuncture (EA). Intracerebroventricular (icv) injection of Som caused a more marked elevation of pain threshold and of EA analgesic effect, but the activity of Ca(2+)-APTase in hippocampus was significantly decreased; The Som and GABA levels in hippocampus and brain stem were decreased by EA analgesia. The Som in hippocampus and brain stem were obviously depleted by icv injection of cycteamine, but without any change of pain threshold and analgesic effect of EA. These results indicated that the exogenous Som of brain potentiated the analgesic effect of EA, however, the decrease of endogenous of some brain regions took part in the process of EA analgesia.
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PMID:[Effect of brain somatostatin on electroacupuncture analgesia of rat]. 875 23

The potential role of somatostatin (SRIF) in the diagnosis and treatment of nonendocrine human cancers is reviewed. There have been many reports of the growth-inhibitory activity of SRIF on normal and transformed cells in vitro. Many processes involved in malignant tumor growth depend on autocrine growth mechanisms, and somatostatin receptors (ssts) are present on many human cancers. It is possible that mutations in ssts result in a loss of check on proliferation in cancer cells. SRIF analogs may have a number of roles in clinical oncology. Use of radiolabeled tracers enables imaging of tumors bearing ssts; newer agents may enable positron emission tomography (PET) analyses or may be used to deliver lethal radiation doses to cells bearing a unique subset of sst. Although the ability of SRIF and its analogs to inhibit cellular proliferation has been shown in vitro, it has yet to be demonstrated in humans with cancer. Clinical improvements seen with SRIF or its analogs in cancer patients may be related to indirect effects, such as pain relief, reduction of gastrointestinal side effects of chemotherapeutic agents, effects on local production of growth factors, and inhibition of tumoral angiogenesis. Thus, with regard to their potential therapeutic role, SRIF analogs are likely to be used only in conjunction with other approaches, such as radiation, immunotherapy, chemotherapy, and growth factor modulation. Further research into the fundamental functions of each of the ssts and the intracellular actions of SRIF analogs will be needed to assess the potential usefulness of the latter in slowing the progression of human cancers.
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PMID:Somatostatin and cancer. 876 96

A 59-year-old man presented with painful subcutaneous nodules on the anterior surfaces of the legs. He had received oral antibiotics and supportive care for presumed cellulitis and thrombophlebitis, but had minimal improvement. Five months earlier, he had undergone pancreaticoduodenectomy for acinar pancreatic carcinoma; at that time, the serum level of amylase had been normal, but the level of lipase was elevated. The patient denied fever, rigors, arthritis/arthralgia, or pleuritic pain. His medications included aspirin, furosemide, ranitidine, and nortriptyline. He denied any allergies. Physical examination revealed numerous firm, tender, erythematous and violaceous, subcutaneous nodules on the lower extremities, with marked bilateral pitting edema (Fig. 1). Skin biopsy of a representative lesion revealed septal panniculitis, consistent with erythema nodosum (Fig. 2). None of the characteristic changes of pancreatic fat necrosis was present. The patient was treated with aspirin, 650 mg orally, q 6 h, and indomethacin, 50 mg orally, q 12 h, but he continued to develop new nodules; prednisone, 60 mg orally was begun. Although he reported improvement in symptoms, the nodules failed to respond clinically and older nodules ulcerated along the medical aspect of the right leg (Fig. 3). The complete blood count was normal, except for hemoglobin, 10.9 mg per dL. Routine serum biochemical studies were also normal, except for albumin, 3.1 mg per dL, LDH, 312 U per L, and SGOT, 51 U per L. Serum amylase was 14 U per L (normal per 30 to 115 U per L) and serum lipase was 54,160 U per L (normal 0 to 200 U per L). Chest roentgenogram and tuberculin skin test were negative. A CT scan of the abdomen revealed extensive liver metastases. A second biopsy of the skin and subcutis of a necrotic nodule revealed lobular panniculitis with the characteristic picture seen in pancreatic fat necrosis (Fig. 4). The patient was presumed to have metastatic pancreatic carcinoma and pancreatic fat necrosis. Nodules subsequently developed on the thighs, arms, hands, wrists, and fingers. He developed arthritis and arthralgias of the ankles, wrists, and hands, bilaterally, and the right knee. Aspiration of a right knee effusion revealed numerous neutrophils, but no evidence of infection. Treatment was begun with the somatostatin analog, octreotide, in increasing doses. During this therapy, the lesions did not progress and new lesions did not appear. There was no change in the lipase level. Inadvertently, octreotide was omitted at discharge, but reintroduction of octreotide was associated with lack of further progression of the nodules, according to the patient's spouse; however the patient became progressively debilitated and his abdominal pain worsened, requiring continuous sedation. His condition deteriorated and he died several weeks after hospital discharge.
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PMID:Fat necrosis with features of erythema nodosum in a patient with metastatic pancreatic carcinoma. 883 28


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