Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four isomers of the Somatostatin analogue H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) were made with beta-MePhe in position 1 and assayed for opioid binding in rat brain, biological activity in MVD and GPI bioassays, and antinociception in mouse warm-water tail flick assays. The analogues displayed varying potencies and biological activities including: simultaneous delta receptor agonism/mu receptor antagonism, mu receptor antagonism, and delta receptor agonism. These analogues demonstrated that the N-terminal residue is important for receptor potency/selectivity and signal transduction. These analogues my represent leads to therapeutic agents that yield analgesia via delta agonist effects, yet lack side effects associated with mu activity.
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PMID:Opioid peptides: simultaneous delta agonism and mu antagonism in somatostatin analogues. 911 58

Using the methods of in situ hybridization (ISHH), ISHH combined with immunocytochemistry ABC and image processing, somatostatin (SOM) mRNA level and coexistence of SOM mRNA and 5-HT in the nucleus raphe dorsalis (RD) of rat were studied in the normal group, noxious stimulation group, simple electroacupuncture group and electroacupuncture analgesia group (EA). A number of oval and fusiform cells with a weak to moderate hybridization signals were mostly distributed in dorsomedial subnucleus of RD and concentrated on rostral part. An increase of SOM mRNA positive cells could be seen in noxious stimulation group and simple electroacupuncture group comparing with the normal group. In EA group the number of SOM mRNA positive cells increased more than any other groups. A few SOM mRNA and 5-HT doubled cells could be seen in RD in the normal group. Most of the doubled cells were distributed in ventromedial, lateral subnuclei of RD. Comparing with the normal group, doubled cells increased in noxious and simple electroacupuncture group and increased significantly in EA group. The results suggest: (1) SOM takes part in modulation of pain. (2) SOM plays a role in EA. (3) Coexistence of SOM mRNA and 5-HT-in RD suggests that SOM and 5 HT interact synergically in EA.
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PMID:[Expression of somatostatin mRNA and coexistence of SOM mRNA and 5-HT in nucleus raphe dorsalis following noxious stimulation and electroacupuncture analgesia]. 938 36

The effects of SP on the electric activities of neurons of spinal dorsal horn and the influence of 5-HT, somatostatin (SOM) on the effects of SP were observed in anesthetized rats with multimicropipete and iontophoresis techniques. It was found that: (1) The microiontophoretically administrating of SP could increase spinal dorsal horn unit discharge. (2) The noxious electrical activity of neurons induced by formalin could be inhibited by microiontophoretically applied SP. (3) The microiontophoretically administrating of 5-HT and SOM could inhibit the SP and formalin evoked unit discharge of neurons in spinal dorsal horn. It was suggested that SP took a double-effect part in modulation of pain transmission and analgesia in spinal cord, 5-HT and SOM inhibited the effect of SP and participated in pain modulation of SP.
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PMID:[Effect of 5-HT and somatostatin on SP and chronic pain initiated electrical activity of neurons in spinal dorsal horn]. 938 37

All horses undergoing coeliotomy for an acute abdominal crisis are at risk of developing ileus and should receive therapy aimed at promoting gastrointestinal function by restoring fluid and electrolyte balance. Adequate analgesia and prevention against peritonitis, bacteraemia and endotoxaemia should be provided. Horses that at the time of surgery have a strangulating or non-strangulating small intestinal obstruction should be considered to be at greater risk of developing a persistent ileus that is refractory to treatment than those horses with lesions involving the large intestine. In horses considered to be at greater risk of developing a persistent ileus, the use of prokinetic agents should be considered. Agents that may be used to improve gastrointestinal motility include adrenergic receptor antagonists, cholinergic agonists, benzamides, dopamine antagonists, macrolide antimicrobials, opiate receptor agonists and antagonists, somatostatin analogues and local anaesthetics. There are limited studies into the use of these agents in the horse. Until further research provides more information on motility disorders following intestinal surgery and the efficacy of prokinetic agents in this species, only selective use of some of these drugs can be recommended.
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PMID:Role of prokinetic drugs for treatment of postoperative ileus in the horse. 957 63

Somatostatin is a neuromodulator and neurotransmitter in the central nervous system. Administration of somatostatin to the spinal cord or brain areas involved in nociception has been shown to result in analgesia. Little information is available about the somatostatin receptor types which may be involved in mediating the neuromodulatory and analgesic effects of the peptide. To define the neuronal systems expressing the sst2(a) receptor in brain areas associated with analgesia, immunohistochemical co-localisation studies were carried out in the periaqueductal grey (PAG) and spinal cord using an antibody specific for the sst2(a) receptor. To further define sst2(a) receptor expressing neurones, sst2(a) receptor immunohistochemistry was combined with retrograde tracing using fluorogold. In the PAG, sst2(a) receptor expressing neurones were found to co-express calbindin D28k (36%), the glutamate transporter EAAC-1 (25%), and GABA transporter GAT-1 ( approximately 10%). A total of 65% of sst2(a) positive neurones projected to the thalamus. In the spinal cord, the sst2(a) receptor shows cellular co-localisation with EAAC-1 and GAT-1. Immunohistochemistry and receptor autoradiography using [125I]BIM 23027 after dorsal rhizotomy of the lumbar dorsal roots, L4 and L5, suggests that the somatostatin sst2(a) receptor is not present on primary afferent neurones. Dorsal hemisections of the mid thoracic cord did not alter the immunohistochemical signal for the somatostatin sst2(a) receptor, providing further evidence for an intrinsic localisation of the receptor protein in the dorsal horn of the spinal cord. These data show that the somatostatin sst2(a) receptor exists on morphologically and neurochemically heterogenous neurones and is closely associated with brain areas involved in analgesia and the modulation of nociception.
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PMID:Identification of somatostatin sst2(a) receptor expressing neurones in central regions involved in nociception. 966 64

Intrathecal administration of octreotide, a stable somatostatin analogue, provides pain relief in patients, and locally applied somatostatin inhibits firing of nociceptive dorsal horn neurons. In the present study, we have raised polyclonal antibodies that specifically detect the somatostatin receptor sst2A and used these antisera for immunocytochemical localization of the receptor protein in the rat spinal cord and dorsal root ganglia. In the superficial layers of the dorsal horn, sst2A-like immunoreactivity (Li) formed a dense network consisting of neuronal perikarya and dendrites which were often closely apposed by, but not co-contained within, somatostatin-14-immunoreactive nerve fibres and terminals. sst2A-Li was resistant to dorsal rhizotomy and did not colocalize with either substance P or calcitonin gene-related peptide suggesting that sst2A-Li was not located to primary afferents, but rather confined to second-order spinal neurons. The position of sst2A-Li perikarya and dendrites in the dorsal horn appeared to be similar to those containing mu-opioid receptor-Li; however, double labelling experiments revealed no instances of coexistence of these two receptors. sst2A-Li was also observed in the dorsal root ganglia predominantly targeted to the somatic plasmalemma of medium size neurons distinct from those expressing somatostatin-14 or delta-opioid receptors. Thus, the present results not only provide a morphological substrate for spinal octreotide analgesia but also show that somatostatin and opioids are poised to modulate nociceptive transmission by distinct anatomical systems.
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PMID:Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia. 987 49

The management of acute pancreatitis is complex. Although numerous medical therapies have been proposed, few interventions have been shown to benefit patients with severe disease. Volume resuscitation, total parenteral nutrition and an adequate analgesia is the unspecific management of acute pancreatitis. Prophylactic antibiotic treatment should be performed in patients with necrotizing disease. Selective decontamination of the digestive tract has shown beneficial effects only in combination with systemic antibiotic therapy. ERCP and endoscopic sphincterotomy should be performed in severe gallstone pancreatitis. Somatostatin, protease inhibitors, hemofiltration and peritoneal lavage are some of the many medications now proven to be of no efficacy. Two clinical prospective trials are now under way to investigate the effects of two promising agents on the course of severe necrotizing pancreatitis: lexipafant, a platelet factor antagonist, and isovolemic hemodilution with dextran.
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PMID:[Acute pancreatitis: reliable and prospective conservative therapy]. 993 54

The effects of microinjection of somatostatin (SS), somatostatin depletor cysteamine (CS) and anti-somatostatin serum (ASSS) on the pain threshold (PT) and electroacupuncture (EA) analgesia were investigated in the rat. The potassium iontophoresis induced tail-flick was used to measure the pain threshold. The "Zusanli" were stimulated with EA. The results indicated that microinjection of SS into necleus raphe magnus (NRM), could elevate PT and enhance EA analgesia. PT and EA analgesia were decreased when SS in NRM was depleted by CS or neutralized by ASSS. These data revealed that SS in NRM plays important roles in inducing analgesia and enhancing electroacupuncture analgesia.
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PMID:[Somatostatin in NRM plays roles in inducing analgesia and enhancing electroacupuncture analgesia]. 1032 66

Insulin crosses the blood-brain barrier (BBB) via receptor-mediated transcytosis and has been suggested to augment uptake of peripheral substances across the BBB. The delta-opioid receptor-selective peptide D-penicillamine(2,5) (DPDPE), a Met-enkephalin analog, produces analgesia via a central nervous system-derived effect. In vitro (K(cell), microl. min(-1). mg(-1)) and in situ (K(in), microl. min(-1). g(-1)) analyses of DPDPE transport (K(cell) = 0.56 +/- 0. 15; K(in) = 0.28 +/- 0.03) revealed significant (P <.01) increases in DPDPE uptake by the BBB with 10 microM insulin (K(cell) = 1.61 +/- 0.25; K(in) = 0.48 +/- 0.04). In vitro cellular uptake was significantly increased (P <.05) at 1 microM insulin, whereas no significant uptake was observed with CTAP (a somatostatin opioid peptide analog) or sucrose (a paracellular diffusionary marker). No significant change in uptake was seen with DPDPE, CTAP, or sucrose in the presence of holo-transferrin (0-100 microM), indicating that the effect of insulin on DPDPE was not a generalized effect of receptor endocytosis. Insulin did not affect P-glycoprotein efflux, a mechanism that has shown affinity for DPDPE. A similar uptake of DPDPE into the brain (64% increase) was seen with the in situ brain perfusion model. Analgesic assessment revealed a significant decline in DPDPE (i.v.)-induced analgesia with increasing concentrations of insulin (i.v., i.c.v., s.c.) in a dose-dependent manner. Thus, insulin significantly increases DPDPE uptake across the BBB by a specific mechanism. The analgesic effect seen with DPDPE and insulin coadministration was shown to decrease, indicating that insulin reduces the analgesic effect within the central nervous system rather than at the BBB.
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PMID:Insulin enhancement of opioid peptide transport across the blood-brain barrier and assessment of analgesic effect. 1108 31

Somatostatin (SST) is in primary afferent neurons and reduces vascular and nociceptive components of inflammation. SST receptor (SSTR) agonists provide analgesia following intrathecal or epidural administration in humans, but neurotoxicity in the central nervous system (CNS) has been reported in experimental animals. With the rationale that targeting peripheral SSTRs would provide effective analgesia while avoiding CNS side effects, the goals of the present study are to investigate the presence of SSTRs on peripheral primary afferent fibers and determine the behavioral and physiological effects of the SST agonist octreotide (OCT) on formalin-induced nociception and bradykinin-induced primary afferent excitation and sensitization in the rat. The results demonstrate that: (1) SSTR2as are present on 11% of peripheral primary afferent sensory fibers in rat glabrous skin; (2) intraplantar injection of OCT reduces formalin-induced nociceptive behaviors; (3) OCT reduces, in a dose-dependent fashion, responses to thermal stimulation in C-mechanoheat sensitive fibers; and (4) OCT reduces the responses of C-mechanoheat fibers to bradykinin-induced excitation and sensitization to heat. Each of these actions can be reversed following co-injection of OCT with the SSTR antagonist cyclo-somatostatin (c-SOM). Thus, activation of peripheral SSTRs reduces both inflammatory pain and the activity of sensitized nociceptors, avoids deleterious CNS side effects and may be clinically useful in the treatment of pain of peripheral origin.
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PMID:Somatostatin receptors on peripheral primary afferent terminals: inhibition of sensitized nociceptors. 1120 95


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