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)

To date about thirty peptides--low-molecular-weight, single-chain amino acid compounds--are known to be distributed widely in the central nervous system within selective neuron pathways. These findings, combined with a large body of neuropharmacological, behavioral, and electrophysiological data, open new horizons in neurobiology, force a reexamination of old and accepted hypotheses, and hold important implications for the clinician. There is evidence that substance P and the opioid peptides play a major role in the pain pathway, particularly at the level of the spinal cord. Available evidence also implicates vasoactive intestinal polypeptide in the control of cerebral circulation, cholecystokinin in the regulation of appetite, and vasopressin and adrenocorticotropic hormone in memory. Many questions, however, remain. For most peptides there is little information on mechanisms of biosynthesis, release, interaction with receptors, and termination of biological effect. Another important question is the interaction of peptides with other neurotransmitters. The evidence that both "classic" neurotransmitters and peptides can be found in the same neuronal necessitates reformulation of Dale's "one neuron, one neurotransmitter" hypothesis. It may be that a single cell, while containing different classes of neurotransmitter, will contain only one member of any particular class. It is not too early to speculate on the role of the numerous and diverse peptides in neuronal tissue and on the implications of peptide abnormalities in a variety of neurological diseases. The answers to these and other questions pose a fascinating challenge to neurobiologist and clinician alike.
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PMID:Neuroendocrinology and brain peptides. 616 92

(1) Capsaicin solution was applied for 15 min around a 1 cm length of sciatic nerve in the mid upper leg of adult rats. (2) Electron microscopic examinations of the nerve in the treated region after 14 days shows no signs of degeneration of either myelinated or unmyelinated fibres attributable to the capsaicin. (3) Fluoride resistant acid phosphatase FRAP disappears from the central terminals of the treated nerve by 7 days. (4) 1.5 mM capsaicin is sufficient to product a complete reduction of FRAP in the spinal cord. (5) The peptides substance P and cholecystokinin (CCK) are markedly depleted in the region of spinal cord terminations of the treated nerve at 14 days. (6) Substance P and CCk are not affected in spinal cord regions other than in the unmyelinated afferent terminal zone. Similarly neurotensin and neurophysin which are not present in afferent fibres are not influenced by capsaicin treatment of the sciatic. (7) It is concluded that there are chemical changes in the spinal cord terminals of fine afferents after local peripheral capsaicin.
Pain 1981 Dec
PMID:Effects of capsaicin applied locally to adult peripheral nerve. II. Anatomy and enzyme and peptide chemistry of peripheral nerve and spinal cord. 617 30

Intrathecal injections of capsaicin (CAP) and 4 other homovanillic acid (HMV) derivatives related to the structure of CAP were carried out. Capsaicin, 1-nonenoylvanillylamide (NVA), HMV-dodecylamide (DCA) (but not HMV-cyclohexylamide (CHA) or HMV-hexadecylamide (HDC] reduced the spinal content of substance P (SP), as measured by radioimmunoassay (RIA), and increased the tail-flick latency. Similar injection of kainic acid and piperine reduced levels of SP but failed to affect the tail-flick latency. None of the agents used affected spinal levels of cholecystokinin (CCK) or vasoactive intestinal peptide (VIP) as measured by RIA. In experiments using in vivo superfusion of the rat spinal cord, CAP, DCA and NVA were found to stimulate release of SP. Capsaicin had no effect on the levels of CCK or VIP immunoreactivity in the spinal superfusate. A tachyphylaxis to the effect of CAP and DCA on spinal SP release was demonstrated. Pretreatment with either agent blocked the releasing effect of the second. Pretreatment with an inactive analogue (HDC) had no effect on the subsequent activity of CAP. Kainic acid and piperine did not induce release of SP from the spinal cord. The relative selectivity of spinally administered capsaicinoids with regard to their effects on the content and release of peptides known to be contained in primary afferents and the presence of a similar structure-activity relationship for depletion and release of SP, desensitization and antinociception suggest the presence of a specific receptor site associated with a specific population of primary afferents through which pain information may pass. Whether SP is an 'afferent pain transmitter' is not clear, but at the least, it appears to serve as a marker for a population of afferents acted upon by spinally administered capsaicinoids.
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PMID:Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia. 620 19

The spinal nociceptive system is the target of various pain depressing agents. It is capable to function without control from the brain. It is activated by tissue damage which, by excitation of nociceptive afferents, evokes activity in axons ascending to the brain (sensory nociceptive response) and in spinal reflex pathways (motor and autonomic responses). The prototype of an analgesic agent, morphine, suppresses nociceptive responses by binding to opiate receptors; it imitates the effect of the transmitter(s) released from endorphinergic neurones. Pentobarbital and diazepam reduce nociceptive (and non-nociceptive) responses by acting on the GABA receptor complex; both drugs facilitate the effect of the transmitter GABA which mediates presynaptic inhibition in the spinal cord. Pentobarbital may produce its effects by an additional action on postsynaptic neurone membranes. Clonidine depresses nociceptive responses, probably by imitating the action of the inhibitory transmitter, noradrenaline. Substance P acts as a "synaptic modulator"; it may facilitate or inhibit nociceptive responses. Ceruletide and cholecystokinin octapeptide depress nociceptive motor responses but do not affect the nociceptive sensory response. This indicates that motor and sensory responses of the spinal nociceptive system are not rigidly linked together. With the help of appropriate drugs, it is possible to manipulate them separately.
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PMID:Pain-depressing agents and the spinal nociceptive system. 620 17

The effect of ceruletide (CRL), a synthetic decapeptide analogue of cholecystokinin, on rest pain and arterial blood flow was evaluated in 8 patients with advanced, occlusive atherosclerosis of the lower extremities. CRL 1, 2, or 4 ng kg-1 or placebo were infused intravenously in random order, and in a double-blind fashion. Pain relief, assessed by a scoring system, was significantly better (p less than 0.01) following the 2 and 4 ng kg-1 doses of CRL (2.71 and 2.66, respectively) than following placebo (0.75). Arterial blood flow was not affected by either CRL in any dose or by placebo. Pretreatment with naloxone, a pure opioid antagonist, abolished the analgesic effect of CRL. Following the 2 ng dose of CRL, beta-endorphin levels were significantly elevated from a basal value of 125 +/- 15 pg/ml to 191 +/- 35 pg/ml 5 h after CRL administration (p less than 0.05). Circulating levels of ACTH, prolactin and GH were not affected by CRL. It is concluded that CRL was effective in relieving ischaemic rest pain, and that the mechanism was related to the release of endogenous opioids.
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PMID:Effect of ceruletide on rest pain in patients with arterial insufficiency of the lower extremity. 629 Feb 28

Decapeptide ceruletide (CRL), chemically related to cholecystokinin and gastrin, proved to have remarkable analgesic properties when administered to a group of 22 burned patients, 15 patients with acute myocardial infarction, and 8 patients suffering from pain caused by malignant tumours with metastases. Its effect was such, that many of the patients required no other analgesics (opiates) even after a prolonged administration (up to 10 days) of CRL. In some of the patients a marked euphoria developed. There were no substantial changes in EEG records during CRL administration in 15 controls, among them 4 epileptics. It is probable that CRL helps to activate the internal analgesic system. In the burned patients cortisol, testosterone, renin, prolactin and tri-iodothyronine (T3) levels in serum (plasma) were measured (radio-immunoassays). CRL did not block the stress response (no drop of increased cortisol levels, no increase in low T3 levels), but it modified (influenced) it (drop of the high renin levels, and a tendency to increase the very low testosterone levels). CRL appears to act as an endorphin releaser, as evidenced by the plasma levels of beta-endorphins (quotations). CRL and similar drugs may represent a new, more physiological and probably safer approach to the management of pain.
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PMID:Endorphin releasers: a new possible approach to the treatment of pain after burns--a preliminary report. 631 91

A prospective double blind placebo controlled study was conducted on 41 patients with a clinical diagnosis of acalculous biliary pain (ABP) and 10 healthy volunteers. Cholecystokinin (CCK) ( Kabivitrum , Uxbridge ) was given intravenously (1 Ivy Dog Unit/kg) over 5 min in a randomized crossover study using normal saline as a placebo infusion. All referred patients had undergone at least one normal oral cholecystogram, abdominal ultrasound and upper gastrointestinal endoscopy before infusions. Twenty-six patients developed pain in response to the CCK infusion and not the placebo, and the pain did not differ from their spontaneous pre-infusion pain as measured by the McGill Pain Questionnaire and a Visual Analogue Pain Scale. Fourteen patients developed no pain with either infusion, and one developed pain with both placebo and CCK. All patients whose pain was reproduced (CCK-positive) underwent cholecystectomy and peroperative cholangiography. Operative findings were normal in all of the CCK-positive group except one in whom a small common bile duct stone was found. Histopathology of resected gallbladders was abnormal in 24 out of 26 cases, but all patients operated on remained pain-free at follow-up (mean 11 months, range 2-24 months). Repeat CCK infusion postoperatively failed to bring on pain in any of the postoperative group. The CCK infusion test is a simple, cheap, bedside or out-patient procedure which will identify true acalculous biliary pain which will respond well to cholecystectomy.
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PMID:Acalculous biliary pain: diagnosis and selection for cholecystectomy using the cholecystokinin test for pain reproduction. 637 34

Ceruletide is a decapeptide isolated from the skin of an Australian frog. Its chemical and biologic relationship to cholecystokinin and its potent relaxant effect on the sphincter of Oddi makes it useful in biliary colic. In this double-blind placebo-controlled experiment, 60 subjects with moderate to severe pain caused by biliary colic were injected with ceruletide, 1 ng/kg iv or with an equal volume of saline solution. Pain in the right hypochondrium, referred pain, and Murphy's sign were scored before and after treatment. Data indicate that ceruletide is effective in biliary colic.
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PMID:Ceruletide analgesia in biliary colic. 647 36

In the search for the most appropriate analgesic for patients with biliary tract and pancreatic pain, the authors compared the effect of morphine and the opiate agonist-antagonist butorphanol on gallbladder contraction and emptying stimulated by cholecystokinin octapeptide. Morphine markedly inhibited gallbladder emptying while butorphanol only slightly delayed it. Compared with morphine, the effect of butorphanol was minimal; the latter, therefore, seems to be a suitable analgesic for the treatment of pain of biliary tract or pancreatic origin.
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PMID:Effect of Morphine and butorphanol on gallbladder emptying. 682 67

The effects of drugs with different mechanisms of action on the human gallbladder smooth muscle are reviewed. Sincalide, the C-terminal octapeptide fragment of cholecystokinin, caused a clinically important contraction of the gallbladder during oral cholecystography in 72% of the patients. Within 8-12 min cystic duct visualization occurred in 44% and common bile duct visualization, in 17%. On the other hand, the standard concentration meal (200 ml cream) caused a more reliable gallbladder contraction in 30 min. One tablet of Baralgin, i.v. proxyphylline (300 mg), and i.v. glycopyrrolate (0.2 mg) had no relaxing effect on the contracted gallbladder during oral cholecystography. Similarly, i.v. metoclopramide (20 mg) and i.v. prostaglandin E2 (25, 50, and 75 micrograms) were ineffective, whereas 1 ampule of Baralgin and 1 ampule of Palerol i.v. caused a significant dilatation. Litalgin i.v. 1 ampule, i.v. papaverine (40 mg), and sublingual nitroglycerin (0.5 mg) had a slight relaxing effect on the smooth muscle of the gallbladder. In an acute attack of pain in a patient with gallstones, i.v. administered Baralgin and Palerol seem to be effective; i.v. Litalgin, i.v. papaverine, and sublingual nitroglycerin may be of value in milder biliary tract disorders, but the benefit of i.v. proxyphylline, i.v. glycopyrrolate, and oral Baralgin is questionable. Metoclopramide can be used as an antiemetic drug in patients with gallstones.
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PMID:The effect of drugs with different mechanisms of action on the contraction of the human gallbladder. 702 33


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