Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin (CT) is a polypeptide hormone produced in the thyroid gland that regulates, blood calcium levels and bone calcium metabolism. The unexpected finding of binding sites for calcitonin in several areas of the brain oriented attention to activities of CT in the central nervous system and also to its antinociceptive action. The first report of this last effect was in 1975, and the many different experimental and clinical data on this topic reported since then are reviewed here. The heterogenous findings have been organized according to the logical classification of animal and human studies. For each of these headings, subheadings such as acute and chronic pain, different kinds of administration and different procedures used to record the results, are considered. The several proposed mechanisms of action, involving serotoninergic, catecholaminergic, Ca2+ fluxes, protein phosphorylation, beta-endorphin production, cyclooxygenase inhibition and histamine interference are also reviewed. Calcitonin, neurotensin, substance P, VIP and, recently, CGRP are some of the non-opioid peptides that have been reported to interfere with pain and that open up a new, alternative way of investigating antinociceptive drugs different than opioid or opioid-like agents. An examination of the state-of-investigation of calcitonin's antinociceptive activity in the last 17 years shows that many experimental studies indicate the existence of this effect, including studies in humans, and this opens up perspectives for therapy with a new class of antinociceptive agents.
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PMID:Calcitonin and its antinociceptive activity: animal and human investigations 1975-1992. 794 19

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

High amounts of neurotensin (NT) are found in the preoptic area of the hypothalamus, an area known to be involved in the regulation of body temperature. It is generally believed that NT is a peptide that produces hypothermia, and several sites in the brain have been proposed to mediate NT-induced hypothermia, including the preoptic area. However, the doses of NT used in these experiments were always very high (microgram order) whereas, according to Goedert, the total brain content of NT in the rat does not exceed 10 ng. We therefore reinvestigated the effects of microinjections of NT in the brain, using high (5 micrograms) and low (50 and 5 ng) doses, into the preoptic area and other brain sites (cerebral ventricles, posterior hypothalamus, and nucleus accumbens), and we also studied, as a comparison, the effects of high and low doses of NT on pain sensitivity in the same sites. The results show that the preoptic area has unique properties in the regulation of body temperature: low doses of NT in the preoptic area produce a hyperthermic response, whereas high doses produce hypothermia. In comparison, NT produces hypothermia in the posterior hypothalamus whatever the dose, and NT has analgesic effects in the preoptic area only at high doses. Besides, NT has no thermic effect, but does have an analgesic effect, in the nucleus accumbens. The selectivity of the actions of high doses of NT, as well as the mechanism of action of NT (possibly an endogenous neuroleptic), are discussed.
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PMID:Low doses of neurotensin in the preoptic area produce hyperthermia. Comparison with other brain sites and with neurotensin-induced analgesia. 870 14

Three-dimensional magnetic resonance cholangiopancreatography is currently the most exciting new imaging technique for chronic pancreatitis. Endoscopy-assisted duodenal intubation during the secretin-cholecystokinin test reduces intubation time in difficult cases. The NBT-para-amino benzoic acid test has been refined to enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and the faecal elastase test are newer highly sensitive and specific tubeless tests. Pain in chronic pancreatitis continues to be a vexing therapeutic issue. Enzyme treatment continues despite criticism. Neurotensin is the new suspected mediator of the feedback mechanism, which is downregulated by enzyme therapy. Steroid ganglion block is an exciting therapeutic tool for pain relief. Endoscopic pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in conjunction with extracorporeal shock wave lithotripsy should be performed early in chronic pancreatitis to prevent parenchymal atrophy with ensuing exocrine and endocrine pancreatic dysfunction. The modified Puestow's procedure preserves endocrine and exocrine pancreatic functions besides relieving pain. Closed loop insulin infusion allows superior management of pancreatic diabetes following near total pancreatectomy. The standardised incidence rate of pancreatic cancer is 16.5 in patients with alcoholic chronic pancreatitis and 100 for tropical chronic pancreatitis. Aggressive treatment protocols combining neo-adjuvant chemoradiation and intra-operative radiation with surgery are being used to improve the prognosis in this dismal complication of chronic pancreatitis.
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PMID:Chronic pancreatitis: diagnosis and treatment. 875 8

The influence of intrathecal injection of Neurotensin (NT) and Anti-NT serum (ANTS) on pain threshold, and electroacupuncture (EA) analgesia in the rat was investigated. The tail-flick induced by potassium iontophoresis was used to measure the pain threshold. The increase of pain threshold was observed within 100 min, after NT injection (2 micrograms), and it was more effective than that of the ACSF injection (P < 0.01). The NT administration could also enhance the EA analgesia. On the contrary, the pain threshold was decreased in ANTS group as compared with that of ACSF control group. The ANTS administration could decreased the role of EA analgesia. Our data show that NT in spinal cord may play an important role in the EA analgesia.
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PMID:[The effect of intrathecal injection of neurotensin on acupuncture analgesia in rats]. 875 21

Supraspinal opioid analgesia is mediated in part by connections between the periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Morphine analgesia elicited from the PAG is respectively decreased by selective serotonergic and opioid receptor antagonists administered into the RVM, and increased by RVM neurotensin antagonists. Since glutamate and excitatory amino acid (EAA) receptors are also active in the RVM, the present study evaluated whether either competitive (AP7) or non-competitive (MK-801) N-methyl-D-aspartate (NMDA) antagonists or a kainate/AMPA (CNQX) antagonist microinjected into the RVM altered morphine (2.5 micrograms) analgesia elicited from the PAG as measured by the tail-flick and jump tests. Mesencephalic morphine analgesia was markedly reduced on both tests after RVM pretreatment with either AP7 (0.01-1 microgram, 0.08-7.8 nmol) or MK-801 (0.03-3 micrograms, 0.04-4.4 nmol). In contrast, small but significant reductions in mesencephalic morphine analgesia occurred on the jump test following CNQX (0.5 microgram, 2.2 nmol) in the RVM. NMDA antagonists did not markedly alter either basal nociceptive thresholds following RVM administration, or mesencephalic morphine analgesia following administration into medullary placements lateral or dorsal to the RVM. These data implicate EAA and particularly NMDA receptors in the RVM in modulating the transmission of opioid pain-inhibitory signals from the PAG.
Pain 1996 Mar
PMID:Excitatory amino acid antagonists in the rostral ventromedial medulla inhibit mesencephalic morphine analgesia in rats. 878 20

The present series of experiments were designed to examine a potential role for central descending pain facilitatory systems in mediating secondary hyperalgesia produced by topical application of mustard oil and measuring the nociceptive tail-flick reflex in awake rats. Topical application of mustard oil (100%) to the lateral surface of the hind leg produced a facilitation of the tail-flick reflex that was significantly reduced in spinal transected animals. Mustard oil hyperalgesia was also inhibited in animals that had received electrolytic lesions in the rostral ventromedial medulla (RVM). Intrathecal (i.t.) administration of the non-selective cholecystokinin (CCK) receptor antagonist proglumide (10 micrograms) prior to mustard oil application completely blocked both the lesser and greater hyperalgesic responses observed in spinal transected and normal animals, respectively, and produced an inhibition of the tail-flick reflex in normal animals. Administration of the selective CCKB receptor antagonist L-365260 i.t. dose-dependently inhibited mustard oil hyperalgesia (ID50 = 364 ng) at doses approximately 5-fold less than the CCKA receptor antagonist devazepide (ID50 = 1760 ng). Similar to spinal proglumide, microinjection of the neurotensin antagonist SR48692 (3.5 micrograms) into the RVM blocked mustard oil hyperalgesia and inhibited the tail-flick reflex. These data suggest that secondary hyperalgesia produced by mustard oil is mediated largely by a central, centrifugal descending pain facilitatory system which involves neurotensin in the RVM and spinal CCK (via CCKB receptors). The inhibition of the tail-flick reflex produced by mustard oil following spinal or supraspinal administration of receptor antagonists suggests concurrent activation of central descending facilitatory and inhibitory systems.
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PMID:Participation of central descending nociceptive facilitatory systems in secondary hyperalgesia produced by mustard oil. 893 Mar 54

After suffering some setbacks since its introduction in 1967, stimulation of the spinal and peripheral nervous systems has undergone rapid development in the last ten years. Based on principles enunciated in the Gate Control Hypothesis that was published in 1968, stimulation-produced analgesia [SPA] has been subjected to intensive laboratory and clinical investigation. Historically, most new clinical ideas in medicine have tended to follow a three-tiered course. Initial enthusiasm gives way to a reappraisal of the treatment or modality as side-effects or unanticipated problems arise. The last and third phase proceeds at a more measured pace as the treatment is refined by experience. This review is divided into three parts as it traces the progress of spinal cord stimulation [SCS] and peripheral nerve stimulation [PNS]. The review commences with a discussion of the theory of SCS and PNS, and is followed by early reports during which it became apparent that the modality is essentially only effective in the treatment of neuropathic pain. The last section describes the modern experience including efficacy in specific types of pain and concludes with recent accomplishments that dramatize the relief of pain which can be achieved in nonoperable peripheral vascular disease or myocardial ischemia. Over the years, a search for those transmitters that might be influenced by spinal cord stimulation focused on somatostatin, cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), neurotensin and other amines, although only substance "P" was implicated. More recently, in animal studies, evidence that GABA-ergic systems are affected may explain the frequent successful suppression of allodynia that follows spinal cord stimulation. During the past eight years, much attention has been directed to studies that use a chronic neuropathic pain model. While PNS held significant promise as a pain relieving modality, early electrode systems and their surgical implantation yielded variable results due to evolving technical and surgical skills. These results dramatically reduced the continued development of PNS, which then gave way to a preoccupation with SCS. Modern development of SCS with outcome studies, particularly in relation to failed back surgery syndrome [FBSS] and the outcome of peripheral nerve surgery for chronic regional pain syndromes, has earned both modalities a place in the ongoing management of patients with intractable neuropathic pain. The last section, dealing with pain of peripheral vascular and myocardial ischemia, is perhaps one of the more exciting developments in stimulation produced analgesia and as the papers discussed demonstrate, can provide a level of analgesia and efficacy that is unattainable by other treatment modalities. SCS and PNS has an important role to play in the management of conditions that are otherwise refractory to conservative or other conventional management.
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PMID:Stimulation of the central and peripheral nervous system for the control of pain. 901 59

Neurotensin has bipolar (facilitatory and inhibitory) effects on pain modulation that may physiologically exist in homeostasis. Facilitation predominates at low (picomolar) doses of neurotensin injected into the rostroventral medial medulla (RVM), whereas higher doses (nanomolar) produce antinociception. SR 48692, a neurotensin receptor antagonist, discriminates between receptors mediating these responses. Consistent with its promotion of pain facilitation, the minimal antinociceptive responses to a 30-pmol dose of neurotensin microinjected into the RVM were markedly enhanced by prior injection of SR 48692 into the site (detected using the tail-flick test in awake rats). SR 48692 had a triphasic effect on the antinociception from a 10-nmol dose of neurotensin. Antinociception was attenuated by femtomolar doses, attenuation was reversed by low picomolar doses (corresponded to those blocking the pain-facilitatory effect of neurotensin) and the response was again blocked, but incompletely, by higher doses. The existence of multiple neurotensin receptor subtypes may explain these data. Physiologically, pain facilitation appears to be a prominent role for neurotensin because the microinjection of SR 48692 alone causes some antinociception. Furthermore, pain-facilitatory (i.e., antianalgesic) neurotensin mechanisms dominate in the pharmacology of opioids; the response to morphine administered either into the PAG or systemically was potentiated only by the RVM or systemic injection of SR 48692. On the other hand, reversal of the enhancement of antinociception occurred under certain circumstances with SR 48692, particularly after its systemic administration.
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PMID:Dose-dependent pain-facilitatory and -inhibitory actions of neurotensin are revealed by SR 48692, a nonpeptide neurotensin antagonist: influence on the antinociceptive effect of morphine. 926 57

The midbrain periaqueductal gray matter (PAG) is an important region for endogenous pain suppression. Nerve terminals containing opioid peptides and neurotensin (NT), as well as high densities of opioid- and NT-receptors, have been demonstrated in the ventromedial PAG. Local administration of opioids or NT in this region induces antinociception in experimental animals. In the present microdialysis study, the effect of opioids on the release of NT in the ventromedial PAG was investigated. Perfusion of the microdialysis probe with 10 microM morphine induced a significant increase (P < 0.05; n = 5) of the extracellular level of NT-like immunoreactivity (NT-LI), while perfusion with a 10-fold higher concentration of morphine had no significant effect on the NT-LI release in the PAG. Also perfusion of the dialysis probe with the mu-opioid receptor-specific agonist [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephaline (DAGO) (1 or 100 microM) induced a significant (P < 0.05; n = 7-9) increase of the NT-LI level. The increase in NT-LI release in response to 1 microM DAGO was both calcium-dependent and naloxone-reversible. Since opioid agonists generally inhibit neuronal activity, an indirect mechanism, involving inhibition of tonically active inhibitory neurons, e.g. gamma-aminobutyric acid (GABA) neurons, could be of importance for the opioid induced release of NT. However, local administration in the PAG of the GABA(A) antagonist bicuculline (0.1-10 microM) or the GABA(A) agonist muscimol (1-100 microM) had no significant effect on the extracellular NT-LI level in the PAG, suggesting that GABAergic mechanisms are not involved in the opioid-induced release of NT-LI. In conclusion, the present data provide in vivo evidence that mu-opioid receptors mediate stimulation of neurotensin release in the PAG.
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PMID:Opioid-induced release of neurotensin in the periaqueductal gray matter of freely moving rats. 945 3


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