Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stress in humans commonly results in gastrointestinal dysfunction, which is characterized by its symptomatology because the etiology is completely unknown. We developed an animal model in which to study the effects of stress on the gastrointestinal tract, and characterized the model as a stressor by evaluating endocrine and analgesic responses to mild restraint. Mild restraint (wrap restraint) elevated plasma levels of adrenocorticotropic hormone and beta-endorphin, and caused analgesia. The different regions of the gastrointestinal tract responded differently to the stress stimulus. Gastric emptying was not affected, small intestinal transit was inhibited, and large intestinal transit was stimulated by stress, and there was an associated increase in fecal excretion. Wrap-restraint stress did not result in the formation of ulcers. There was a strong correlation between stress-induced adrenocorticotropic hormone release and stress-induced intestinal dysfunction over a 24-h period that suggested a circadian influence. However, neither exogenous adrenocorticotropic hormone nor beta-endorphin had any effect on intestinal transit. Furthermore, neither adrenalectomy nor hypophysectomy prevented the response of the intestine to stress, suggesting that neither adrenal nor pituitary-derived factors are responsible for mediating the effects of stress on the gut. We conclude that wrap-restraint stress produces different effects on different regions of the intestine, suggesting that the small and large intestines are independently regulated and can respond differently to different stimuli. There were similarities between the intestinal effects of wrap-restraint stress in rats and intestinal symptoms associated with stress and irritable bowel syndrome in humans. Therefore, wrap restraint may be an appropriate animal model in which to study stress-related intestinal dysfunction. The mechanisms by which stress affects intestinal transit are still unresolved; however, the intestinal effects of stress are not mediated by either pituitary or adrenally derived factors.
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PMID:Stress-induced changes in intestinal transit in the rat: a model for irritable bowel syndrome. 282 44

Placebo, defined as any therapeutic procedure, without any specific activity, given deliberately to have an effect on a patient, symptom, syndrome or disease, has a great impact in the evaluation of drug response. The possible pathways via which the possible effect brings about clinical and physiological changes remain unknown, but a humoral mechanism seems to be implicated in some placebo effects (e.g. placebo-induced analgesia). The placebo effect depends on many factors, including the type of patient, the personality of the physician, the doctor-patient relationship and the type and even the colour of the drug preparation. Placebo control is important particularly when the disease is characterized by frequent spontaneous periods of acute exacerbation and remission. Functional (such as dyspepsia and irritable bowel syndrome) and organic (such as peptic ulcer and inflammatory bowel disease) gastrointestinal diseases have got great benefit from placebo-controlled clinical trials. In such trials the more effective the placebo is, the more difficult it will be to demonstrate the efficacy of active drug in statistical terms. Nevertheless, provided the use of placebo be ethical for a given condition, placebo-controlled trials are the only objective way of assessing correctly drug response in patients.
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PMID:Placebo and placebo effect: their impact on the evaluation of drug response in patients. 771 18

It was investigated whether central pain mechanisms including the endogenous antinociceptive system were involved in functional dyspepsia defined as: abdominal pain without abnormal findings. Pain sensitivity was measured by an ischaemic pain test comparing 21 functional dyspepsia patients with two control groups: 1) 24 patients with organic abdominal pain, and 2) 13 healthy pain-free controls. The endogenous opioids beta-endorphin, met-enkephalin immunoreactivity, and dynorphin immunoreactivity were measured in cerebrospinal fluid (CSF) from nine patients with functional dyspepsia and pain-free controls undergoing minor surgery while under spinal analgesia. There was no significant difference between the groups in pain sensitivity, but subdivision of the functional dyspepsia group showed that individuals with pain and no symptoms of irritable bowel syndrome (IBS) were significantly more sensitive to ischaemic pain than functional dyspepsia patients with IBS. The CSF beta-endorphfin concentration was significantly decreased in the functional dyspepsia group as compared with the controls. There were no significant group differences regarding met-enkephalin immunoreactivity and dynorphin immunoreactivity. Because of post-lumbar-puncture headache, this part of the investigation was suspended after nine patients. Functional dyspepsia is probably a pain syndrome with decreased central antinociceptive activity.
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PMID:[Reduced concentration of beta-endorphin in cerebrospinal fluid and reduced pain tolerance in patients with functional dyspepsia]. 783 29

We investigated whether central pain mechanisms including the endogenous antinociceptive system are involved in functional abdominal pain--that is, abdominal pain without abnormal findings at routine examinations. beta-Endorphin, met-enkephalin immunoreactivity, and dynorphin immunoreactivity were measured in cerebrospinal fluid (CSF) from nine patients with long-lasting functional abdominal pain and nine pain-free controls undergoing minor surgery while under spinal analgesia. Furthermore, pain sensitivity was evaluated with an ischaemic pain test comparing 21 functional abdominal pain patients with two control groups: 1) 24 patients with organic abdominal pain due to duodenal ulcer, gallstone, or urinary tract calculi, and 2) 13 healthy pain-free controls. The CSF beta-endorphin concentration was significantly decreased in the functional abdominal pain group as compared with nine matched controls (P = 0.01). Met-enkephalin and dynorphin immunoreactivities were normal. This part of the investigation was suspended after nine patients had been tested, because of post-lumbar-puncture headache. With regard to pain sensitivity, no significant difference between the three groups was shown, but subdivision of the functional abdominal pain group showed that individuals with pain and no symptoms of irritable bowel syndrome (IBS) were significantly more sensitive to pain than functional abdominal pain patients with IBS and healthy controls (P = 0.04).
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PMID:Decreased cerebrospinal fluid beta-endorphin and increased pain sensitivity in patients with functional abdominal pain. 790 92

Acupuncture has been used for various gastrointestinal (GI) conditions. Voluminous data support the effect of acupuncture on the physiology of the GI tract, including acid secretion, motility, neurohormonal changes, and changes in sensory thresholds. Much of the neuroanatomic pathway of these effects has been identified in animal models. A large body of clinical evidence supports the effectiveness of acupuncture for suppressing nausea associated with chemotherapy, postoperative state, and pregnancy. Prospective randomized controlled trials have also shown the efficacy of acupuncture for analgesia for endoscopic procedures, including colonoscopy and upper endoscopy. Acupuncture has also been used for a variety of other conditions including postoperative ileus, achalasia, peptic ulcer disease, functional bowel diseases (including irritable bowel syndrome and nonulcer dyspepsia), diarrhea, constipation, inflammatory bowel disease, expulsion of gallstones and biliary ascariasis, and pain associated with pancreatitis. Although there are few prospective randomized clinical studies, the well-documented physiological basis of acupuncture effects on the GI tract, and the extensive history of successful clinical use of acupuncture, makes this a promising modality that warrants further investigation.
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PMID:Acupuncture for gastrointestinal and hepatobiliary disorders. 1010 29

This study investigated the combined effect of neonatal maternal separation and acute psychological stress on pain responses in adult rats. Long-Evans dams and their male pups were reared under two conditions: 1) 180 min daily maternal separation (MS180) on postnatal days 2-14 or 2) no handling or separation (NH). At 2 mo of age, visceromotor responses to graded intensities of phasic colorectal distension (10-80 mmHg) at baseline as well as following acute 60 min water avoidance stress (WA) were significantly higher in MS180 rats. Both groups showed similar stress-induced visceral hyperalgesia in the presence of naloxone (20 mg/kg ip). MS180 rats had smaller stress-induced cutaneous analgesia in the tail-flick test compared with NH rats, with a residual naloxone-resistant component. MS180 rats showed an enhanced fecal pellet output following WA or exposure to a novel environment. These data suggest that early life events predispose adult Long-Evans rats to develop visceral hyperalgesia, reduced somatic analgesia, and increased colonic motility in response to an acute psychological stressor, mimicking the cardinal features of irritable bowel syndrome.
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PMID:Neonatal maternal separation alters stress-induced responses to viscerosomatic nociceptive stimuli in rat. 1180 52

A study was conducted to determine whether changes in expected pain levels, desire for pain relief, or anxiety contribute to an increase in placebo analgesia over time as well as to determine whether placebo analgesic effects of IBS patients are related to endogenous opioid mechanisms. Twenty-six women with IBS were exposed to rectal stimulation (35 or 55 mmHg for 30 s) and tested under natural history (NH), rectal placebo (RP) and rectal lidocaine (RL) conditions. During all conditions, 16 patients were given saline intravenously (to test for a placebo effect) and 10 patients were given naloxone intravenously (to test naloxone antagonism of the placebo effect) on a double blind basis. Patients rated expected pain level, desire for pain relief and anxiety at 2 and 22 min after the onset of NH, RP, and RL conditions and they rated actual pain intensity at 5-min intervals for 40 min. There was a large and significant placebo effect (P<0.001) that increased over time. Ratings of expected pain levels, desire for pain relief and anxiety decreased over time and contributed to more variance in placebo and lidocaine responses during the last half of the session. These changes suggest that a reduction in negative emotions may be central to placebo effects. There was no significant difference between psychological mediators (desire, expectation, anxiety) or the placebo effect in the saline and naloxone groups, indicating that neither the psychological mediators nor the placebo analgesic effect were associated with endogenous opioids in this clinically related paradigm.
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PMID:Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms. 1591 Nov 61

There is convincing evidence that acupuncture (AP) is effective for the treatment of postoperative and chemotherapy-induced nausea/vomiting, as well as postoperative dental pain. Less convincing data support AP's efficacy for chronic pain conditions, including headache, fibromyalgia and low back pain. There is no evidence that AP is effective in treating addiction, insomnia, obesity, asthma or stroke deficits. AP seems to be efficacious for alleviating experimental pain by increasing pain thresholds in human subjects and it appears to activate analgesic brain mechanisms through the release of neurohumoral factors, some of which can be inhibited by the opioid antagonist naloxone. In contrast to placebo analgesia, AP-related pain relief takes some time to develop and to resolve. Furthermore, repetitive use of AP analgesia can result in tolerance that demonstrates cross-tolerance with morphine. However, it appears that not all forms of AP are equally effective for providing analgesia. In particular, electro-AP seems to best deliver stimuli that activate powerful opioid and nonopioid analgesic mechanisms. Thus, future carefully controlled clinical trials using adequate electro-AP may be able to provide the necessary evidence for relevant analgesia in chronic pain conditions, such as headache, fibromyalgia, irritable bowel syndrome and low back pain.
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PMID:Mechanisms of acupuncture analgesia for clinical and experimental pain. 1673 14

Previous experiments found that placebos produced small decreases in neural activity of pain-related areas of the brain, yet decreases were only statistically significant after termination of stimuli and in proximity to when subjects rated them. These changes could reflect report bias rather than analgesia. This functional magnetic resonance imaging (fMRI) study examined whether placebo analgesia is accompanied by reductions in neural activity in pain-related areas of the brain during the time of stimulation. Brain activity of irritable bowel syndrome patients was measured in response to rectal distension by a balloon barostat. Large reductions in pain and in brain activation within pain-related regions (thalamus, somatosensory cortices, insula, and anterior cingulate cortex) occurred during the placebo condition. Results indicate that decreases in activity were related to placebo suggestion and a second factor (habituation/attention/conditioning). Although many factors influence placebo analgesia, it is accompanied by reduction in pain processing within the brain in clinically relevant conditions.
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PMID:Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. 1696 84

Some studies, suggesting the involvement of I(2)-imidazoline binding sites (I(2)-IBS) in morphine analgesia modulation, prompted us to examine on mice antinociceptive assays the effect produced by 1 (phenyzoline), that in view of its high I(2)-IBS affinity and high I(2)-IBS selectivity with regard to I(1)-IBS, alpha(2)-adrenoreceptors and mu-opioid receptors might be considered the first interesting I(2)-IBS ligand. The study was also applied to its ortho phenyl derivative 2 (diphenyzoline), designed and prepared in order to produce a possible modification of the biological profile of 1. Diphenyzoline (2) retains a significant I(2)-IBS selectivity with regard to I(1)-IBS, alpha(2)-adrenoreceptors and mu-opioid receptors. Moreover, by the functional assays 1 and 2 proved inactive at all alpha(2)-adrenoreceptors subtypes up to 10(-3) M. As expected, phenyzoline and diphenyzoline, which are structurally related, highlighted an interesting "positive" or "negative", respectively, morphine analgesia modulatory effect. In fact, 1 (s.c. 10 mg/kg) enhanced morphine analgesia (60% and 40% in mouse tail-flick and mouse hot-plate, respectively), while 2 (s.c. 10 mg/kg) decreased it (-41% and -20%, respectively). The ability to decrease morphine analgesia had never been observed before in I(2)-IBS ligands. These effects were not affected by i.p. treatment of animals with yohimbine (a selective alpha(2)-adrenoreceptor antagonist, 0.625 mg/kg) or efaroxan (an I(1)-IBS/alpha(2)-adrenoreceptor antagonist, 1.0 mg/kg). In contrast, they were completely reversed by i.p. treatment of animals with idazoxan (an I(2)-IBS/alpha(2)-adrenoreceptor antagonist, 2 mg/kg). Moreover, compound 2, in mouse tail-flick test, was able to potentiate by 23% the naloxone-induced decrease of morphine analgesia. Therefore, the results of this study indicate the crucial involvement of I(2)-IBS in the morphine analgesia modulatory effects of 1 and 2.
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PMID:Involvement of I2-imidazoline binding sites in positive and negative morphine analgesia modulatory effects. 1708 13


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