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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the N-methyl-D-aspartate (NMDA) receptor has been reported to be involved in the mechanisms that underlie thermal hyperalgesia produced by the intraplantar injection of carrageenan. As NMDA-mediated thermal hyperalgesia produced in models of acute and persistent pain have been reported to involve production of nitric oxide, we examined the role of nitric oxide in both the development and maintenance of the thermal hyperalgesia produced by the intraplantar injection of carrageenan. In addition, we examined the role of nitric oxide in the maintenance of the mechanical hyperalgesia produced by intraplantar injection of carrageenan. Prior to the intraplantar injection of carrageenan (2 mg in 100 microliters) there was no significant difference in thermal withdrawal latencies or mechanical withdrawal thresholds between the left and right hindpaws. Three hours after injection of carrageenan into the left hindpaw, rats showed evidence of a significantly faster thermal withdrawal latency and lower mechanical withdrawal threshold of the left hindpaw compared to the right hindpaw. In addition, the left hindpaw was significantly increased in size (diameter) compared with the right hindpaw. In these same rats, the intrathecal administration of saline, NG-nitro-L-arginine methyl ester (L-NAME; 2-200 nmol) or the inactive enantiomer, NG-nitro-D-arginine methyl ester (D-NAME; 200 nmol) did not produce any significant change in thermal nociceptive withdrawal latencies in the non-injected paw. However, administration of L-NAME (2-20 nmol), but not saline or D-NAME produced a dose dependent and reversible block of the thermal hyperalgesia for a period of up to 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of nitric oxide in the development and maintenance of the hyperalgesia produced by intraplantar injection of carrageenan in the rat. 807 88

Two matched groups of postmenopausal patients were treated respectively with calcitonin or calcitonin and an arginine-lysine-glycerophosphoric acid-lactose association. The rationale underlying this therapy took the form of data in the literature which indicated an action of these amino acids and lactose on calcium absorption and on the metabolism of protein components in the skeletal structure. The following tests were performed: mineralometric evaluation, evaluation of painful symptoms and intake of pain-relieving drugs, serum levels of calcium, phosphorus, alkaline phosphatase, osteocalcin, parathormone, and calciuria and hydroxyproline. These parameters were assayed at the beginning and end of treatment which lasted six months. The results, or in other words the comparison between the two groups, basal or after treatment, and the values recorded before and after treatment in each group, enable the authors to affirm that the administration of the arginine-lysine-glycerophosphoric acid-lactose association leads to an increase in bone density and plasma osteocalcin, a reduction in painful symptoms and analgesic intake, and a reduction in the serum levels of parathromone and hydroxyproline. Data reported in the literature support the conclusion that the results obtained are the consequence of an improved intestinal absorption calcium. It is highly probable that the protein components of the association administered, arginine-lysine-glycerophosphoric acid-lactose, also exercise a direct action on osteoblasts and on the metabolism of bone matrix protein components.
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PMID:[Experience regarding the use of arginine-lysine-lactose treatment in menopausal osteoporosis]. 808 36

1. This study was designed to investigate the role of bradykinin (BK), as well as the subtype of BK receptors involved, in formalin-induced hindpaw pain in the mouse by use of selective B1 and B2 receptor antagonists. In addition, we have analysed whether or not BK may be involved in formalin-induced hindpaw oedema in the mouse. 2. The pretreatment of animals with captopril (2 and 5 mg kg-1, s.c.) significantly increase the first and the second phases of formalin-induced pain. 3. Co-injection of the selective B1 receptor antagonist des-Arg9[Leu8]-BK (0.2-0.4 nmol/paw), together with formalin, caused graded and similar inhibitions of both phases of formalin-induced pain. Similar results were obtained with the B2 antagonists NPC 349 (D-Arg[Hyp3,Thi5,8-D-Phe7]-BK) and NPC 567 (D-Arg[Hyp3, D-Phe7]-BK) (0.2 and 0.6 nmol/paw). Higher concentrations of these antagonists (1 nmol/paw) failed to antagonize formalin-induced pain. 4. The new potent and selective B2 receptor antagonists, Hoe 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-BK), NPC 17731 (D-Arg[Hyp3, trans-4-propoxy-D-proline (transpropyl)7, Oic8]-BK), and NPC 17761 (D-Arg[Hyp3, trans-4-propoxy-D-proline (trans thiophenyl)7, Oic8]-BK) (0.02 to 1.0 nmol/paw), also caused significant inhibitions of both phases of formalin-induced pain. When Hoe 140 was injected subcutaneously 30 min before formalin injection (9.9 and 99 nmol kg-1), it significantly attenuated both phases of formalin-induced pain. The putative non-peptide BK antagonist, MV 8612 (1.6 to 9.6 nmol/paw), but not MV 8608 (5.5 to 33 nmol/paw), caused a graded inhibition of both phases of formalin induced pain, being, however, more active against the first phase.5. The pretreatment of animals with morphine (2.6 to 13 micromol kg-1, s.c.) caused dose-dependent and equipotent inhibitions of both phases of formalin-induced pain. In contrast, in domethacin (2.7 to 27 micromol kg-1) antagonized only the second phase of formalin-induced pain.6. The B2 receptor antagonists, Hoe 140, NPC 17731, NPC 17761, NPC 349 and NPC 567, all caused a significant inhibition of formalin-induced hindpaw oedema. A similar inhibition was also observed within domethacin but not with captopril or morphine.7. Our results provide strong evidence for the important role of endogenous BK, acting through both B1 and B2 receptors, in the genesis of both phases of formalin-induced persistent pain in the mouse. In addition, the current results also demonstrate that the inflammatory oedema associated with the later phase of formalin-induced pain seems to be mediated by endogenous BK, via activation of B2 receptors.
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PMID:Evidence for participation of B1 and B2 kinin receptors in formalin-induced nociceptive response in the mouse. 822 Aug 79

To assess the possible role of spinal nitric oxide (NO) synthesis in nociceptive processing, we examined the effect of intrathecal (i.t.) injection of arginine analogs that act as alternate substrates for NO synthase and thus inhibit NO production. NG-nitro-L-arginine ester (r-NAME) and NG-monomethyl-L-arginine (L-NMMA) produced a dose-dependent, stereospecific inhibition of the second phase (10-60 min; ED50, 135 and 246 nmol) of the formalin test with minimal effect on the first phase (0-9 min; ED50 > 1.1 mumol). The inhibitory action of L-NAME was dose-dependently reversed by i.t. L-arginine (ID50, 4.9 mumol) but not by D-arginine (ID50 > 14 mumol). The suppression of the second-phase formalin response by L-NAME was similar whether administered before or after formalin injection into the rat paw. Spinal administration of L-NAME (370 nmol), but not D-NAME (3.7 mumol), also blocked thermal hyperalgesia induced by i.t. injection of N-methyl-D-aspartate (NMDA; 6.8 nmol). The effect of L-NAME was reversed by L-arginine (4.7 mumol) but not with D-arginine (14 mumol). None of the compounds, L-NAME, D-NAME or L-arginine, when injected alone, had any effect on normal thermal response latencies or on the 52.5 degrees C hot plate. These studies indicate that modulation of spinal NO synthesis can diminish the facilitated processing of afferent activity which is induced by a continued afferent barrage (second phase of the formalin test). This hyperalgesic component appears initiated by the activation of a spinal NMDA receptor that, through the generation of NO, leads to the observed augmented processing of afferent input and the associated hyperalgesic component of the subsequent pain behavior.
Pain 1993 Sep
PMID:Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats. 823 43

Kinins exert a variety of biological actions and have been implicated in the pathogenesis of inflammation, pain, asthma, and other diseases. Kinins act through specific receptors that are widespread and belong to two major categories, B1 and B2. B2 has been cloned and shown to be of the rhodopsin type, consisting of seven hydrophobic membrane domains connected by extracellular and intracellular loops. Recent pharmacological findings from various laboratories suggest the existence of new receptor types, which have been named B3, B4, and B5. These findings are analysed critically, especially with respect to the criteria that have been used for affirming the existence of new receptor entities. The analysis is restricted to data obtained in isolated organs, almost exclusively smooth muscle preparations. Criteria for receptor characterization and classification are the order of potency of agonists and the apparent affinities of antagonists. The analysis reveals that receptors for bradykinin and related kinins are of two types, B1 and B2. B1 mediates the rapid acute response (smooth muscle contraction or relaxation) as well as some effects occurring more slowly (e.g., collagen synthesis). B1 receptor functions have been shown to be modulated by interleukins. B2 receptors are responsible for most of the kinins' biological effects, including arterial vasodilatation, plasma extravasation, venoconstriction, activation of sensory fibers (e.g., fibers for pain), and stimulation of the release of prostaglandins, endothelium-dependent relaxing factor (from endothelia), noradrenaline (from nerve terminals and adrenals), and other endogenous agents. The pharmacological characteristics of the receptor sites (B2) mediating this array of biological effects show differences between species, and two B2 receptor subtypes are proposed, namely B2A (rabbit, dog, and possibly man) and B2B (guinea pig, hamster, rat). B2A and B2B receptor subtypes have been characterized by using fairly selective agonists and competitive antagonists (e.g., D-Arg[Hyp3, D-Phe7,Leu8]BK). Noncompetitive antagonists (non-equilibrium), such as HOE 140, do not discriminate between B2A and B2B subtypes. Species differences cannot account for the multiplicity of receptors that have been proposed for rat vas deferens, pre- and post-junctional sites, and rat uterus, guinea pig ileum, and rat blood pressure. The existence of hypothetical new receptor sites was based on data obtained with partial agonists and have not been substantiated by data obtained with potent pure antagonists. The B3 receptor, proposed to explain the unusual behaviour of the guinea pig tracheal response to kinins, has to be carefully reconsidered after the finding that HOE 140 acts as a pure antagonist on this tissue and shows a fairly high affinity for the tracheal site.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Receptors for bradykinin and related kinins: a critical analysis. 830 93

There has been recent evidence linking bradykinin (BK) receptors with inflammation. This study has investigated the involvement of BK receptors in two models of persistent inflammatory hyperalgesia in rats. In a Freund's adjuvant-induced hyperalgesia model and an ultraviolet (UV)-induced hyperalgesia model in rats the specific B2 antagonist, D-Arg[Hyp3, Thi5, D-Tic7, Oic8]-BK (HOE 140), was either ineffective or weakly active in reversing hyperalgesia. The specific B1 antagonist, des-Arg9, [Leu8]-BK, was effective in reversing or preventing the development of hyperalgesia in both Freund's adjuvant-induced hyperalgesia and UV-induced hyperalgesia. The B1 agonist, des-Arg9-BK, produced a small exacerbation of hyperalgesia in both models. Data suggest that in persistent inflammatory conditions in the rat bradykinin B1 receptors are involved in the accompanying hyperalgesia.
Pain 1993 May
PMID:Antinociceptive activity of the bradykinin B1 and B2 receptor antagonists, des-Arg9, [Leu8]-BK and HOE 140, in two models of persistent hyperalgesia in the rat. 839 71

Recent studies have suggested that a spinal cholinergic system is important in spinal nociceptive modulation. In the present study, the role of a nitric oxide (NO)-generating system in spinal cholinergic modulation of nociception was examined in awake rats. Intrathecal (i.t.) administration of the cholinergic muscarinic receptor antagonist atropine produced a dose-dependent (1.4-14.4 nmol) decrease in the mechanical threshold for tail withdrawal, which was reversed rapidly (2-3 min) by subsequent i.t. administration of the NO precursor, L-arginine (10 pmol to 10 nmol). Intrathecal administration of L-arginine alone (10 pmol to 10 nmol) produced a dose-dependent increase in the mechanical nociceptive withdrawal threshold of the tail. The reflexive withdrawal of the tail produced by noxious heat was not significantly affected by i.t. administration of either atropine or L-arginine. Inhibition of the NO-cGMP pathway by i.t. administration of either Nw-nitro-L-arginine methyl ester (L-NAME, 10 nmol) or methylene blue (10 nmol) significantly enhanced the magnitude and prolonged the time course of the decrease in the mechanical threshold for tail withdrawal produced by i.t. pretreatment with atropine (1.4 nmol). Neither L-NAME nor methylene blue affected mechanical withdrawal thresholds in rats pretreated with saline. These data suggest that the production of endogenous NO is required for tonic inhibition of spinal nociceptive mechanical transmission. Moreover, the present data support the speculation that there exists in the lumbar spinal cord a tonic, cholinergic modulation of NO synthase.
Pain 1993 Jul
PMID:Endogenous nitric oxide is required for tonic cholinergic inhibition of spinal mechanical transmission. 839 74

An ethnopharmacological survey showed that home remedies prepared with flowers, fruits and roots of Psychotria colorata (Wild. ex R. & S.) Muell. Arg. (RUBIACEAE) are used by Amazonian caboclos as pain killers. These data led to the evaluation of analgesic activity of extracts of P. colorata, using the formalin, writhing and tail-flick methods. This paper reports the Naloxone reversible opioid-like analgesic activity of alkaloids present in leafs and flowers of P. colorata.
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PMID:Analgesic activity of Psychotria colorata (Willd. ex R. & S.) Muell. Arg. alkaloids. 858 97

Analgesia has been reported to be facilitated by supraspinal nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In the rostromedial medulla, an important pain-suppressing region, iontophoretically delivered 8-bromo-cGMP excited most single recorded cells (9/10), and methylene blue (a guanylyl cyclase inhibitor) inhibited all cells (7/7). Nitrite and ferrous ions together, shown voltammetrically ex vivo to yield nitric oxide (NO), excited some cells (14/28) and inhibited others (7/28). Methylene blue blocked excitation (3/3) but not inhibition (4/4) by the putative NO. Spontaneous or glutamate-evoked firing was gradually inhibited (23/32) or unaffected by N omega-nitro-L-arginine (a NO synthase inhibitor), but was mostly inhibited by L-arginine (the NO precursor) (23/26), although a rapid onset militated against elevated NO production. These substances, excepting L-arginine, produced changes consistent with an excitatory cGMP-NO cascade contributing to analgesia.
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PMID:Excitation of cells in the rostral medial medulla of the rat by the nitric oxide-cyclic guanosine monophosphate messenger system. 858 98

Islet autotransplantation can prevent surgically induced diabetes after total pancreatectomy in adults; however, the efficacy of this procedure has not been established in children. The authors report the case of a 12-year-old boy who underwent total pancreatectomy and islet autotransplantation for intractable pain caused by idiopathic chronic pancreatitis. Islets were prepared from the excised pancreas by collagenase digestion and mechanical dispersion. The resultant preparation, containing 109,500 islets, was injected into the recipient's liver via the portal vein. No complication from the pancreatectomy or transplant occurred. Postoperatively, the patient had complete relief of abdominal pain. He remained insulin-independent, with normal fasting blood glucose and hemoglobin A1c levels, for 21/2 years. Preoperatively, the acute insulin response and the rate of glucose disappearance (Kg) were 213 microU/mL and 2.14% (respectively) after intravenous administration of 20 g of glucose. Although lower than pretransplantation values, both insulin response and Kg remained normal at 4 months (88 microU/mL; Kg, 1.01%); however, these decreased further, to below normal, by 2 years posttransplantation (10 microU/mL; Kg, 0.67%). Two-and-a-half years after transplantation, fasting hyperglycemia (> 200 mg/dL) was evident, and the patient was begun on exogenous insulin. Five years posttransplantation he remains insulin-dependent with a fasting serum C-peptide level of 0.20 ng/mL, which increased to 0.35 ng/mL in response to intravenous arginine, indicating sustained islet function. During the documented decreases in insulin secretion and Kg posttransplantation, the patient's body weight increased by 65% (from 34 to 56 kg) as a result of normal growth; the number of transplanted islets relative to body mass decreased accordingly, from 3,200 to 1,950 islets per kilogram of body weight. In this case, the number of islets transplanted likely could not meet the increased insulin demands of the larger body mass. Thus, exogenous insulin supplementation was needed to prevent hyperglycemia. In conclusion, insulin independence was initially established in a child by islet autotransplantation after total pancreatectomy. The failure of the islets to maintain normoglycemia long-term suggests that a sufficient number must be transplanted (to meet the demands of normal growth and development) for sustained insulin independence.
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PMID:Islet Autotransplantation after total pancreatectomy in a child. 863 66


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