UMLS:C0030193 - FACTA Search

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

Increasing the ectopic uterine motility is the major reason for primary dysmenorrhea. This motility is the basis for several symptoms including for pain is the main complaints of patients with primary dysmenorrhea. There are several mechanisms, which initiate dysmenorrhea. Therefore, different compounds can be employed to control its symptoms. In long-term therapy, combination of oestrogens and progestins may be useful. In short-term therapy, dysmenorrhea sometimes non-steroidal anti-inflammatory drugs (NSAIDs) are used. Most of NSAIDs in long-term therapy show severe adverse effects. In an attempt to find agents with less adverse effect the fennel essential oil (FEO) was chosen for this investigation. In this article, effects of FEO on the uterine contraction and estimation of LD(50) in rat were described. For assessment of pharmacological effects on the isolated rat uterus, oxytocin (0.1, 1 and 10 mu/ml) and prostaglandin E(2) (PGE(2)) (5x10(-5) M) were employed to induce muscle contraction. Administration of different doses of FEO reduced the intensity of oxytocin and PGE(2) induced contractions significantly (25 and 50 microg/ml for oxytocin and 10 and 20 microg/ml PGE(2), respectively). FEO also reduced the frequency of contractions induced by PGE(2) but not with oxytocin. LD(50) of FEO was obtained in the female rats by using moving average method. The estimated LD(50) was 1326 mg/kg. No obvious damage was observed in the vital organs of the dead animals.
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PMID:The effect of fennel essential oil on uterine contraction as a model for dysmenorrhea, pharmacology and toxicology study. 1144 53

Visceral inflammation is thought to play an important role in the sensitization of low and high threshold mechanosensory and polymodal afferents and to recruit silent nociceptors. Yet, little is known about the potential role of the mediators involved in nociceptor sensitization to mechanical stimulation as compared to heat sensitization in the skin. In the present study we developed a new isolated preparation of the mouse colon which allowed to apply controlled mechanical distensions. Excised segments of colon from CD mice were immersed in synthetic interstitial fluid (SIF) exposing the serosal surface during 5 min to different types of noxious stimuli; the increase in neuropeptide and PGE(2) release were analyzed (by EIA technique). Capsaicin, heat and pH 5.2 were able to induce significant increases in calcitonin gene related peptide (CGRP) release (14.6-, 5.1-, and 2.3-fold over baseline), however, only capsaicin induced a significant increase in substance P (SP) levels (1.8-fold over baseline). When pH 3.4 was used, a massive liberation of both CGRP and SP was obtained (14- and 15-fold from baseline) which was Ca(2+)-independent and not recovering, suggesting unphysiological release. Mechanical distensions in the noxious range (45, 60 and 90 mmHg) evoked a long-linear graded release of CGRP (1.3-, 1.6- and 2.6-fold over baseline) and of PGE(2) (1.9- 3.8-, 12.3-fold over baseline). Only the 90 mmHg distension evoked a significant increase of SP (1.9-fold over baseline). We conclude that the mouse colon preparation is a suitable model to study inflammatory and nociceptive mechanisms in viscera. Furthermore, a potentially important and yet unexplored role of PGE(2) in noxious visceral distension has been revealed.
Pain 2001 Sep
PMID:Substance P, calcitonin gene related peptide and PGE2 co-released from the mouse colon: a new model to study nociceptive and inflammatory responses in viscera, in vitro. 1151 80

Prostanoids sensitize sensory afferents during inflammation. However, their role in neuropathic pain is still unclear. We analyzed the actions of prostanoids, non-selective (indomethacin) or selective (celecoxib and NS-398) cyclooxygenase-2 (COX or COX-2) inhibitors, on the ectopic activity of dorsal root ganglia (DRG) and dorsal horn (DH) neurons in a model of neuropathic injury. Extracellular recordings of DRG and DH neurons and cardiovascular measurements were performed on anesthetized, paralyzed and artificially ventilated adult male Sprague-Dawley rats whose sciatic nerve had been transected. PGD(2), PGE(2), PGF(2alpha), carbaprostacyclin (cPGI(2); a stable prostacyclin analog), and carbocyclic thromboxane (cTXA(2)) were administered at cumulative doses (0.0001-5 mg/kg, i.p.) at 5 or 10 min intervals. Only cPGI(2) significantly increased the DRG and DH activity in a dose-dependent manner, with ED(50) values of 0.05 (0.01-0.96) and 0.69 (0.11-1.04) mg/kg, respectively. The other prostanoids did not significantly increase activity, although they reduced heart rate for up to 5 min following administration. Time course experiments with single doses of cPGI(2) (1 mg/kg, i.v.) increased DH discharge rate 3-17 min after injection. Indomethacin (3 mg/kg, s.c.), but not celecoxib or NS-398 (both at 6 mg/kg, s.c.), reduced both DRG and DH activity. Our results indicate that cPGI(2) excites DRG and DH neurons of neuropathic rats, and may suggest a role for IP prostanoid receptors in pain episodes associated with nerve injury. The inhibitory effect of indomethacin, but not celecoxib or NS-398, on ectopic activity may suggest that a tonic generation of PGI(2) by COX-1 could contribute to neuropathic pain.
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PMID:A stable prostacyclin analog enhances ectopic activity in rat sensory neurons following neuropathic injury. 1151 14

PGs have been shown to modulate skeletal muscle protein metabolism as well as inflammation and pain. In nonskeletal muscle tissues, the over the counter analgesic drugs ibuprofen and acetaminophen function through suppression of PG synthesis. We previously reported that ibuprofen and acetaminophen inhibit the normal increase in skeletal muscle protein synthesis after high intensity eccentric resistance exercise. The current study examined skeletal muscle PG levels in the same subjects to further investigate the mechanisms of action of these drugs in exercised skeletal muscle. Twenty-four males (25 +/- 3 yr) were assigned to 3 groups that received the maximal over the counter dose of ibuprofen (1200 mg/d), acetaminophen (4000 mg/d), or a placebo after 10-14 sets of 10 eccentric repetitions at 120% of concentric 1 repetition maximum using the knee extensors. Preexercise and 24 h postexercise biopsies of the vastus lateralis revealed that the exercise-induced change in PGF(2alpha) in the placebo group (77%) was significantly different (P < 0.05) from those in the ibuprofen (-1%) and acetaminophen (-14%) groups. However, the exercise-induced change in PGE(2) in the placebo group (64%) was only significantly different (P < 0.05) from that in the acetaminophen group (-16%). The exercise-induced changes in PGF(2alpha) and PGE(2) were not different between the ibuprofen and acetaminophen groups. These results suggest that ibuprofen and acetaminophen have a comparable effect on suppressing the normal increase in PGF(2alpha) in human skeletal muscle after eccentric resistance exercise, which may profoundly influence the anabolic response of muscle to this form of exercise.
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PMID:Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen. 1160 May 86

Splanchnic nerve fibers innervating the stomach were studied in anesthetized rats; 997 fibers in the T(9) or T(10) dorsal roots were identified by electrical stimulation of the splanchnic nerve. Thirty-one fibers responded to gastric distension. Extrapolated response thresholds ranged between 0 and 53 mmHg; seven fibers had thresholds for response > or =30 mmHg. Thermo- and/or chemosensitivity was tested in 18 of the 31 fibers. Four of twelve fibers responded to intragastric perfusion of heated saline; none of eight fibers tested responded to perfusion of cold saline. Infusion of glucose, L-arginine, or potassium oleate produced no change in resting activity. Intragastric instillation of 12% glycerol or an inflammatory soup (bradykinin 10(-5) M, PGE(2) 10(-5) M, serotonin 10(-5) M, histamine 10(-5) M, and KCl 10(-3) M) and prior heat stimulation sensitized responses to distension. The results reveal the presence of low- and high-threshold mechanosensitive fibers in the splanchnic innervation of the stomach. These fibers have the ability to sensitize, and they likely contribute to pain and altered sensations that can arise from the stomach.
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PMID:Characterization of mechanosensitive splanchnic nerve afferent fibers innervating the rat stomach. 1170 50

(89)SrCl(2) is currently used as a systemic radioactive palliative treatment for painful osseous metastases associated with an osteoblastic reaction in bone. However, the biological mechanism by which (89)SrCl(2) mediates pain palliation remains unclear. In this study, attempts were made to elucidate the mechanisms by which (89)SrCl(2) might influence pain at these sites. Both the direct radiotoxic effects of (89)SrCl(2) on cell viability and its influence on cellular biosynthetic activity were investigated. The direct radiotoxic effects of (89)SrCl(2) and X-rays were compared using the prostate carcinoma cell line, PC-3. Comparable effects upon PC-3 cell viability were seen in response to exposure to an equivalent dose given by (89)SrCl(2) and X-rays (2 Gy). Experiments to investigate the indirect action of (89)SrCl(2) exposure employed the MC3T3-E1 cell line and focused on their production of Prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6). Exposure of the MC3T3-E1 cell line to (89)SrCl(2) resulted in an increased production of PGE(2) in a concentration-dependent manner. No increased PGE(2) production was seen by the MC3T3-E1 cells in response to X-ray exposure either in the presence or absence of SrCl(2). IL-6 was produced by the MC3T3-E1 cells in response to (89)SrCl(2) exposure via a PGE(2)-mediated pathway. This study demonstrates the release of potent biochemical modifiers of bone turnover in response to the systemically applied radiotherapeutic (89)SrCl(2). This strongly suggests the mechanism of pain palliation by (89)SrCl(2) is likely to result from a complex interaction of direct and indirect radiation-induced effects.
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PMID:Biochemical responses in cultured cells following exposure to (89)SrCl(2): potential relevance to the mechanism of action in pain palliation. 1172 Aug 44

Nociception evoked prostaglandin (PG) release in the spinal cord considerably contributes to the induction of hyperalgesia and allodynia. To evaluate the relative contribution of cyclooxygenase-1 (COX-1) and COX-2 in this process we assessed the effects of the selective COX-1 inhibitor SC560 and the selective COX-2 inhibitor celecoxib on formalin-evoked nociceptive behaviour and spinal PGE(2) release. SC560 (10 and 20 mg/kg) significantly reduced the nociceptive response and completely abolished the formalin-evoked PGE(2) raise. In contrast, celecoxib (10 and 20 mg/kg) was ineffective in both regards, i.e. the flinching behaviour was largely unaltered and the formalin-induced PGE(2) raise as assessed using microdialysis was only slightly, not significantly reduced. This suggests that the formalin-evoked rapid PG release was primarily caused by COX-1 and was independent of COX-2. Mean free spinal cord concentrations of celecoxib during the formalin assay were 32.0 +/- 4.5 nM, thus considerably higher than the reported IC50 for COX-2 (3-7 nM). Therefore, the lack of efficacy of celecoxib is most likely not to be a result of poor tissue distribution. COX-2 mRNA and protein expression in the spinal cord were not affected by microdialysis alone but the mRNA rapidly increased following formalin injection and reached a maximum at 2 h. COX-2 protein was unaltered up to 4 h after formalin injection. The time course of COX-2 up-regulation suggests that the formalin-induced nociceptive response precedes COX-2 protein de novo synthesis and may therefore be unresponsive to COX-2 inhibition. Considering the results obtained with the formalin model it may be hypothesized that the efficacy of celecoxib in early injury evoked pain may be less than that of unselective NSAIDs.
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PMID:Effects of selective COX-1 and -2 inhibition on formalin-evoked nociceptive behaviour and prostaglandin E(2) release in the spinal cord. 1172 70

Despite the crucial role that prostaglandins (PGs) have in the sensitization of the central nervous system to pain, their cellular and molecular targets leading to increased pain perception have remained elusive. Here we investigated the effects of PGE(2) on fast synaptic transmission onto neurons in the rat spinal cord dorsal horn, the first site of synaptic integration in the pain pathway. We identified the inhibitory (strychnine-sensitive) glycine receptor as a specific target of PGE(2). PGE(2), but not PGF(2 alpha), PGD(2) or PGI(2), reduced inhibitory glycinergic synaptic transmission in low nanomolar concentrations, whereas GABAA, AMPA and NMDA receptor-mediated transmission remained unaffected. Inhibition of glycine receptors occurred via a postsynaptic mechanism involving the activation of EP2 receptors, cholera-toxin-sensitive G-proteins and cAMP-dependent protein kinase. Via this mechanism, PGE(2) may facilitate the transmission of nociceptive input through the spinal cord dorsal horn to higher brain areas where pain becomes conscious.
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PMID:PGE(2) selectively blocks inhibitory glycinergic neurotransmission onto rat superficial dorsal horn neurons. 1174 May 1

The purpose of this project was to evaluate the analgesic efficacy of misoprostol when combined with ibuprofen or diclofenac Na. Animal experiments using the inflamed rat paw formalin model suggested that misoprostol potentiates the analgesic effect of some NSAIDs (nonsteroidal anti-inflammatory drugs) including diclofenac Na but not propionic acid derivatives or opiates. The dental pain model was used to evaluate the clinical relevance of this interaction. Patients received a single oral dose of study medication following surgical removal of impacted teeth. Patients were medicated for moderate to severe postsurgical pain and then filled in an analgesic diary for a 6-h observation period. Several blood samples were taken over the observation period. In addition, microdialysis samples were taken directly from the extraction socket and were analyzed for immunoreactive prostaglandin E(2) levels. The studies were single-dose, parallel group and double-blind assays. In the first study, 70 patients received an oral dose of either placebo (n = 13), misoprostol 200 &mgr;g (n = 18), ibuprofen 200 mg (n = 19), or the combination of misoprostol + ibuprofen (n = 20). Misoprostol alone demonstrated a small analgesic effect compared to placebo. Both the ibuprofen and combination groups were substantially more effective than placebo but not different from each other. The combination group had higher ibuprofen blood levels during the first 45 min but had a lower C(max) and longer time to T(max). The second study evaluated oral doses of placebo (n = 11), misoprostol 200 &mgr;g (n = 21), diclofenac Na 50 mg (n = 18), and the combination of misoprostol + diclofenac Na (n = 20). Relative to placebo, misoprostol performance was similar to the first study. When the results of the two studies were combined, there was a small, but statistically significant, analgesic effect for misoprostol. Diclofenac Na was superior to both placebo and to misoprostol alone. The combination was the most effective treatment, and for hours 4--6 it was significantly better than diclofenac Na alone. Analysis of the blood samples showed an earlier and higher peak effect for the diclofenac Na group compared to the combination, and the combination again had a lower C(max). The microdialysis probe assays demonstrated that misoprostol depressed PGE(2) levels at the peripheral site of trauma over the first 2 h after surgery. These pilot studies used small samples, and the results only suggest trend effects. Both studies demonstrated that misoprostol 200 &mgr;g, a prostaglandin analog, does have an analgesic effect. When combined with ibuprofen, there was no potentiation of analgesia. In contrast, the combination of misoprostol + diclofenac Na demonstrated an enhanced peak effect, total effect for pain intensity difference and pain relief (sum pain intensity difference [SPID] and total pain relief [TOTPAR]), and
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PMID:The Analgesic Interaction of Misoprostol with Nonsteroidal Anti-Inflammatory Drugs. 1186 59

Pain is one of the cardinal signs of inflammation. A number of inflammatory mediators have been shown in animal models to induce or augment pain. Of particular interest are the prostaglandins (PGs), which are arachidonic acid metabolites and can be pharmacologically regulated by cyclooxygenase inhibitors, the nonsteroidal anti-inflammatory drugs (NSAIDs). Indeed, NSAIDs are potent modulators of pain sensitivity. They are thought to mediate their hypoalgesic action through inhibition of prostaglandin production. However, indiscriminate inhibition of prostaglandin synthesis also creates a significant number of clinical side effects, among them gastrointestinal toxicity. With the introduction of misoprostol, a PGE(1) analog, a large number of investigative possibilities are opened. We have proposed to study the effect of misoprostol in an in vitro pain model. Our model, created by culturing primary sensory neurons isolated from dorsal root ganglions, was then differentiated by nerve growth factor and subjected to electrical stimulation. Substance P release following electrical stimulation was quantitated by radioimmunoassay. We found that misoprostol augmented substance P release in a dose-related manner. With 100 ng/ml of misoprostol added, there was a 45% increase in substance P release as compared to control. PGE(1) and PGE(2) addition at similar concentration caused a similar degree of increase in substance P release. Thus, acute addition of misoprostol to cultured sensory neurons appears to sensitize them to release more substance P. Our result does not necessarily imply that misoprostol will cause pain clinically. In our study, misoprostol at 10 ng/ml has no effect on substance P release. Because the plasma concentration of misoprostol is in the picogram per milliliter range, misoprostol most likely does not have a pain potentiation effect at the recommended therapeutic dose. Our data indicated that misoprostol at therapeutic dose has an insignificant effect on substance P release from primary sensory neuron.
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PMID:Modulation of Substance P Release in Primary Sensory Neurons by Misoprostol and Prostaglandins. 1186 61

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