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

The effects of prostaglandin I2 on the discharge properties of fine articular afferents (group III and group IV fibers) in the cat were examined by extracellular recordings from single units dissected from the medial articular nerve of the knee joint. Prostaglandin I2 was applied intra-arterially close to the joint in doses of 0.3-30 micrograms per 0.3 ml bolus injection, and its effects on the spontaneous activity as well as on discharges evoked by mechanical and chemical stimulation (bradykinin) were monitored. Prostaglandin E2 was also applied and the effects of prostaglandins I2 and E2 on particular units were compared. An excitatory effect of prostaglandin I2 was observed in 49% of 37 group III and in 37% of 27 group IV units. A sensitization to passive movements of the joint occurred in 71% of 31 group III and 48% of 21 group IV units. Sixty-seven per cent of 32 units (groups III and IV) were both excited and sensitized by prostaglandin I2 to movements of 27% were sensitized but not excited. In 64% of 11 group III and 63% of eight group IV units studied the responses to bradykinin were enhanced by prostaglandin I2. Prostaglandin E2 had qualitatively similar effects as prostaglandin I2 but excited and sensitized a lower proportion of articular afferents. Forty-one per cent of the units were sensitive to both prostaglandins but 26% of the fibers were only sensitive to prostaglandin I2. None of the units was exclusively sensitive to prostaglandin E2. In general, the excitatory and sensitizing effects of prostaglandin E2 had a longer duration than those exerted by prostaglandin I2. We conclude that prostaglandin I2 increases the sensitivity to mechanical stimuli as well as to chemical stimulation by bradykinin in the majority of articular group III and group IV fibers. Moreover, in a large proportion of articular afferents, prostaglandin I2 had an excitatory effect. Thus, prostaglandin I2 may be an inflammatory mediator which is important for inflammation-evoked activity in slowly conducting afferents and it may participate in the development of arthritic hyperalgesia and pain.
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PMID:Inflammatory mediators and nociception in the joint: excitation and sensitization of slowly conducting afferent fibers of cat's knee by prostaglandin I2. 140 58

Normal nociceptors are sensitized by hyperalgesic mediators such as eicosanoids and tachykinins. The possibility that these mediators contribute to hyperalgesic pain associated with neural injury was investigated by examining their effects on the excitability of injured afferent nerve endings. In amounts that sensitize normal nociceptors and are hyperalgesic in normal skin, the eicosanoids prostaglandin I2 (PGI2), and 8(R),15(S)-dihydroxyicosatetraenoic acid (8(R),15(S)-diHETE) both excited some C-fibers in chronic neuromas of rat sciatic nerve. In contrast, the selective tachykinin-receptor agonists septide and senktide did not excite C-fibers. None of the mediators affected A-fibers. We conclude that PGI2 and 8(R),15(S)-diHETE may contribute to post-injury pain and hyperalgesia by an action on injured afferent endings.
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PMID:Eicosanoids, but not tachykinins, excite C-fiber endings in rat sciatic nerve-end neuromas. 161 Oct 31

Prostaglandin E2 and prostacyclin (prostaglandin I2) produce hyperalgesia in animals and humans. Because there is evidence that prostaglandins contribute to pain maintained by sympathetic nervous system activity, we evaluated whether sympathetic postganglionic neurons synthesize these hyperalgesic prostaglandins, and whether production of prostaglandins by these neurons can contribute to sensitization of primary afferent nociceptors. Intradermal injection of arachidonic acid but not linoleic acid, in the rat hindpaw, produces a decrease in mechanical nociceptive threshold. This hyperalgesic effect is prevented by indomethacin, an inhibitor of prostaglandin synthesis or by prior surgical removal of the lumbar sympathetic chain. To test the hypothesis that sympathetic postganglionic neurons are the source of prostaglandins, we measured production of prostaglandin E2 and 6-keto-prostaglandin F1 alpha (the stable metabolite of prostacyclin) by homogenates of adult rat sympathetic postganglionic neurons from superior cervical ganglia. These homogenates produced significant amounts of prostaglandin E2 and 6-keto-prostaglandin F1 alpha, and most of this production is eliminated by neonatal administration of 6-hydroxydopamine which selectively destroys sympathetic postganglionic neurons. These results demonstrate that sympathetic postganglionic neurons produce prostaglandins, and supports further the hypothesis that the release of prostaglandins from sympathetic postganglionic neurons contributes to the hyperalgesia associated with sympathetically maintained pain.
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PMID:Production of hyperalgesic prostaglandins by sympathetic postganglionic neurons. 250 43

1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli, and hyperalgesia as assessed by the hot plate test. We characterized prostaglandin E receptor subtypes (EP1-3) involved in these sensory disorders by use of 7 synthetic prostanoid analogues. 2. Sulprostone (EP1 < EP3) induced allodynia over a wide range of dosages from 50 pg to 5 micrograms kg-1. The maximal allodynic effect was observed at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. This sulprostone-induced allodynia showed a time course similar to that induced by PGE2. 3. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and 16,16-dimethyl PGE2 (EP1 = EP2 = EP3) were as potent as PGE2 in inducing allodynia, and more potent than sulprostone. Butaprost (EP2), 11-deoxy PGE1 (EP2 = EP3), MB 28767 (EP3), and cicaprost (prostaglandin I2 (IP-) receptor) induced allodynia, but with much lower scores. 13,14-Dihydro-15-keto PGE2, a metabolite of PGE2, did not induce allodynia. 4. 16,16-Dimethyl PGE2 as well as PGE2 induced hyperalgesia over a wide range of dosages (16,16-dimethyl PGE2: 5 pg-0.5 micrograms kg-1 PGE2: 50 pg-0.5 micrograms kg-1) with two apparent peaks at 0.5 ng kg-1 and 0.5 micrograms kg-1. Sulprostone (EP1 < EP3) and 17-phenyl-omega-trinor PGE2 (EP1 > EP3) showed a bell-shaped hyperalgesia at lower doses of 5 pg-5 ng kg-1 and 50 pg-50 ng kg-1, respectively. MB28767 (EP3)showed a monophasic hyperalgesic action over a wide range of dosages at 50 pg-S5 Microg kg-1. Butaprost(EP2) induced hyperalgesia at doses higher than 50 ng kg-1.5. These results demonstrate that PGE2 may exert allodynia through the EP1-receptor and hyperalgesia through EP2- and EP3-receptors in the mouse spinal cord.
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PMID:Characterization of EP-receptor subtypes involved in allodynia and hyperalgesia induced by intrathecal administration of prostaglandin E2 to mice. 792 97

The effects of beta-phorbol 12,13-dibutyrate (PDBu) on the discharge properties of slowly conducting knee joint afferents (group III and group IV fibers) were studied to determine the role of protein kinase C in nociception. Extracellular single unit recordings were made from small filaments dissected from the medial articular nerve in cats anesthetized with alpha-chloralose. PDBu was applied intra-arterially close to the joint in concentrations of 10(-6) up to 10(-4) M. The afferents were classified as low-threshold and high-threshold units with regard to their sensitivity to passive noxious and innocuous movements of the knee joint. Following PDBu application, an excitation occurred in 28% of the group III and in 40% of the group IV fibers. An enhancement of responses to passive movements of the joint (sensitization) occurred in 37% of group III and 19% of group IV afferents. In summary, 37.5% of the low-threshold and 50% of the high-threshold fibers proved to be sensitive to PDBu. Most of the PDBu-positive units responded also to bradykinin, whereas only a few PDBu-positive units were sensitive to prostaglandin I2 and E2. We conclude from these results that, in a distinct population of slowly conducting joint afferents, protein kinase C is likely to be involved in the process of transduction. Thus, pain and hyperalgesia may be mediated at least partly by intracellular mechanisms that are linked to protein kinase C.
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PMID:The effects of phorbol ester on slowly conducting afferents of the cat's knee joint. 838 19

Prostanoids are a group of bioactive lipids working as local mediators and include D, E, F and I types of prostaglandins (PGs) and thromboxanes. Prostacyclin (PGI2) acts on platelets and blood vessels to inhibit platelet aggregation and to cause vasodilatation, and is thought to be important for vascular homeostasis. Aspirin-like drugs, including indomethacin, which inhibit prostanoid biosynthesis, suppress fever, inflammatory swelling and pain, and interfere with female reproduction, suggesting that prostanoids are involved in these processes, although it is not clear which prostanoid is the endogenous mediator of a particular process. Prostanoids act on seven-transmembrane-domain receptors which are selective for each type. Here we disrupt the gene for the prostacyclin receptor in mice by using homologous recombination. The receptor-deficient mice are viable, reproductive and normotensive. However, their susceptibility to thrombosis is increased, and their inflammatory and pain responses are reduced to the levels observed in indomethacin-treated wild-type mice. Our results establish that prostacyclin is an antithrombotic agent in vivo and provide evidence for its role as a mediator of inflammation and pain.
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PMID:Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. 926 2

Prostaglandins are generated through two isoforms of the enzyme cyclooxygenase, the constitutively expressed cyclooxygenase (Cox)-1 and Cox-2, which is induced at sites of inflammation. Selective inhibition of Cox-2 is desirable as this may avoid the gastropathy and platelet inhibition seen with nonselective agents. Moreover, these agents will allow us to examine the relative contribution of the two isoforms to prostaglandin formation in man. We examined the activity of nimesulide, a Cox-2 selective nonsteroidal antiinflammatory drug, in vitro against purified enzymes and in vivo in man. Nimesulide 100 mg twice daily or aspirin 300 mg three times daily were administered randomly for 14 days to 20 subjects complaining of musculoskeletal pain. Serum thromboxane B2 was determined as an index of Cox-1 activity and endotoxin-induced prostaglandin E2 formation in whole blood as an index of Cox-2 activity. Urinary excretion of prostaglandin metabolites was determined by GC/MS. Nimesulide was highly selective against ovine Cox-2, so that at concentrations attained in vivo, it had no effect on Cox-1 but completely suppressed Cox-2. Aspirin markedly inhibited serum thromboxane B2 (181.92 +/- 19.77 to 2.83 +/- 0.96 ng/ml, P <. 002), whereas nimesulide had very little effect (207.53 +/- 47.30 to 181.15 +/- 54.59 ng/ml). In contrast, nimesulide suppresses endotoxin-induced prostaglandin E2 formation (35.03 +/- 8.73 to 2.62 +/- 0.95 ng/ml, P =.002). As expected, aspirin reduced TX metabolite excretion, whereas nimesulide had no significant effect. In contrast, both compounds suppressed PGI2 formation to the same extent. The findings suggest that TX is largely Cox-1 derived. Moreover, Cox-2 is expressed in man and generates prostaglandin I2.
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PMID:Selective cyclooxygenase-2 inhibition by nimesulide in man. 980 83

The effects of the prostaglandin I2 derivative beraprost sodium (Dorner) on ankle pressure index (AP; ankle joint-to-upper extremity systolic pressure ratio), subjective symptoms, and intermittent claudication were investigated in diabetic patients with arteriosclerosis obliterans (ASO). Forty patients (25 men and 15 women), mean age 63.9 years, were enrolled in this study. ASO was grade I in 30 patients, grade II in seven, grade III in one, and grade IV in two according to the Fontaine classification. They were administered six tablets (20 microg/tablet) of beraprost sodium daily for 6 months. At 3 and 6 months, API had significantly increased and symptoms such as coldness, numbness, and lack of feeling in the lower extremities were significantly improved. Ten evaluable patients increased ambulatory distance by approximately threefold, suggesting an improvement in intermittent claudication. Adverse reactions were experienced by five (12.5%) of the 40 patients (one case each of headache, dull headache, pain in the posterior region of the neck, heartburn, stomach discomfort, and anemia), but all were mild and resolved without treatment. Beraprost sodium was shown to improve API and symptoms in the lower extremities in diabetic patients with ASO, suggesting that it is useful in treating peripheral circulatory disorders in such patients.
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PMID:Effects of beraprost sodium (Dorner) in patients with diabetes mellitus complicated by chronic arterial obstruction. 1186 12

Prostacyclin (PGI2) is well known to play crucial roles in induction of edema and pain behavior in the periphery. In the present study, we investigated the central role of PGI2 in inflammatory pain. Intraplantar injection of carrageenan markedly induced the expression of prostacyclin receptor (IP receptor) mRNA with the maximum at 6 h, coincidently induction of the inducible form of cyclooxygenase (COX-2), although IP receptor mRNA was weakly expressed in the spinal cord of naive mice. Intrathecal administration of the IP agonist cicaprost induced mechanical hyperalgesia 6 h after carrageenan injection. These results suggest that PGI2 is involved in pain transmission at the spinal cord following expression of IP receptor mRNA induced by peripheral inflammation.
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PMID:Central nociceptive role of prostacyclin (IP) receptor induced by peripheral inflammation. 1192 2

Topical capsaicin is believed to alleviate pain by desensitizing the vanilloid receptor 1 (VR1) at the peripheral nerve endings. Here, we report that an up-regulation of VR1 expression on myelinated fibers contributes to the antihyperalgesic effect of capsaicin cream in streptozotocin (STZ)-induced diabetic neuropathic pain. Intravenous injection of STZ (200 mg/kg) in mice caused rapid onset of diabetes within 24 h. Thermal and mechanical hyperalgesia developed by 3 days after STZ injection and persisted at all time points tested until 28 days. There was also hyperalgesic response to intraplantar (i.pl.) prostaglandin I2 (PGI2) agonist-induced nociception in such mice. Application of capsaicin cream dose dependently reversed the thermal, mechanical, and PGI2 agonist-induced hyperalgesia observed in the diabetic mice. The i.pl. injection of capsaicin solution (0.4 microg/20 microl) produced nociceptive biting-licking responses in control mice, and these responses were significantly increased in STZ-induced diabetic mice. After neonatal capsaicin-treatment, which destroys most unmyelinated C-fibers, the i.pl. capsaicin-induced biting-licking responses were almost abolished. However, in neonatal capsaicin-treated diabetic mice, the i.pl. capsaicin-induced biting-licking responses reappeared. The i.pl. capsaicin-induced biting-licking responses were blocked by the competitive VR1 antagonist capsazepine. All these results suggest an increase in capsaicin receptor on myelinated fibers due to diabetes. Finally, we confirmed the up-regulation of VR1 expression on myelinated primary afferent neurons of diabetic mice by immunohistochemistry. Together, our results suggest that increased expression of VR1 on myelinated fibers might contribute to the antihyperalgesic effect of topical capsaicin in diabetic neuropathic pain.
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PMID:Increased expression of vanilloid receptor 1 on myelinated primary afferent neurons contributes to the antihyperalgesic effect of capsaicin cream in diabetic neuropathic pain in mice. 1272 50


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