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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty subjects were given a placebo (intravenous saline), which was described as a known pain killer, once a week for 3 consecutive weeks. Experimental ischemic arm pain was produced prior to the placebo and again 1 h later. In a double blind procedure, half of the subjects received 10 mg of naloxone after placebo; the remaining subjects received naloxone vehicle. In addition to the placebo session, there were control and naloxone sessions each week to determine the normal changes in pain and the effect of naloxone on the pain, respectively, when no placebo was given. Significant placebo-induced analgesia was demonstrated, and a group of consistent placebo responders was identified. Although naloxone alone had no effect on the experimental pain, naloxone diminished the analgesic effectiveness of the placebo, suggesting that endogenous opioids are involved in producing placebo-induced analgesia.
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PMID:Partial antagonism of placebo analgesia by naloxone. 630 40

A 6-year-old boy presented with a large, rapidly growing osteosarcoma of the upper humerus and severe neuropathic arm pain. Despite large doses of morphine (100 micrograms/kg/hr), which resulted in intermittent somnolence and respiratory depression, his pain was poorly controlled. An interscalene brachial plexus catheter was inserted, and bupivacaine was injected on ten occasions over 5 days, with markedly improved analgesia and decreased opioid requirement. Cancer pain in children can be controlled by opioids in 95% of cases; however, circumstances such as intractable neuropathic pain may require specific regional anesthetic techniques.
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PMID:Continuous brachial plexus neural blockade in a child with intractable cancer pain. 808 45

This systematic review assesses six experimental studies into the mechanism of placebo analgesia in human subjects suffering from clinical pain or experimentally induced ischaemic arm pain. Due to their sophisticated designs, these studies probably provide the best evidence that placebo analgesia exists. They also indicate that placebo analgesia is mediated by endogenous opiates. However, there seems to be room for additional studies.
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PMID:Is placebo analgesia mediated by endogenous opioids? A systematic review. 971 45

We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain. Different types of placebo analgesic responses were evoked by means of cognitive expectation cues, drug conditioning, or a combination of both. Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine. Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone. Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone. Morphine conditioning alone (without expectation cues) induced a naloxone-reversible placebo effect. By contrast, ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially. Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive. Therefore, we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or, otherwise, naloxone-insensitive, depending on the procedure used to evoke the placebo response. These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia, and this balance is crucial for the activation of opioid or nonopioid systems. Expectation triggers endogenous opioids, whereas conditioning activates specific subsystems. In fact, if conditioning is performed with opioids, placebo analgesia is mediated via opioid receptors, if conditioning is performed with nonopioid drugs, other nonopioid mechanisms result to be involved.
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PMID:Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. 987 Sep 76

Individual differences in pharmacokinetics and pharmacodynamics, the type of pain and the method of drug administration can account for the response variability to analgesics. By integrating a clinical and an experimental approach, we report here that another important source of variability is represented by individual differences in non-specific (placebo) activation of endogenous opioid systems. In the first part of this study, we analyzed the effectiveness of buprenorphine, tramadol, ketorolac and metamizol in the clinical setting, where the placebo effect was completely eliminated by means of hidden infusions. We found that the hidden injections were significantly less effective and less variable compared with open injections (in full view of the subject), suggesting that part of the response variability was due to non-specific factors (placebo). Since we could not administer the opioid antagonist, naloxone, to these patients, in the second part of this study, we induced experimental ischemic arm pain in healthy volunteers and found that, as occurred in clinical pain, the analgesic response to a hidden injection of the non-opioid ketorolac was less effective and less variable than an open injection. Most importantly, we obtained the same effects by adding naloxone to an open injection of ketorolac, thus blocking the opioid-mediated placebo component of analgesia. These findings indicate that both the psychological (hidden injection) and pharmacological (naloxone) blockade of the placebo response reduce the effectiveness of, and the response variability to, analgesic drugs. Therefore, an important source of response variability to analgesics appears to be due to differences in non-specific activation of endogenous opioid systems.
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PMID:Response variability to analgesics: a role for non-specific activation of endogenous opioids. 1179 Apr 84

Placebo-activated endogenous opioids act on pain mechanisms inducing analgesia, as well as on the respiratory centers inducing respiratory depression. Here, we show that placebo analgesia is accompanied by a reduced beta-adrenergic activity of the heart. We measured heart rate during placebo-induced expectation of analgesia, both in the clinical and the laboratory setting. In the clinical setting, we found that the placebo analgesic response to an electrical noxious stimulus was accompanied by a reduced heart rate response. In order to investigate this effect from a pharmacological viewpoint, we reproduced the same effect in the laboratory setting by using experimental ischemic arm pain. We found that the opioid antagonist naloxone completely antagonized both placebo analgesia and the concomitant reduced heart rate response, whereas the beta-blocker propranolol antagonized the placebo heart rate reduction, but not placebo analgesia. By contrast, both placebo responses were present during muscarinic blockade with atropine, indicating no involvement of the parasympathetic system. In order to better understand the effects of naloxone and propranolol, we performed a spectral analysis of the heart rate variability for the identification of the sympathetic and parasympathetic components, and found that the beta-adrenergic low frequency (0.15 Hz) spectral component was reduced during placebo analgesia, an effect that was reversed by naloxone. These findings indicate that placebo analgesia is accompanied by a complex cascade of events which affect the cardiovascular system.
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PMID:Placebo analgesia and the heart. 1262 Jun 3

The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms, although little is known about their role in different circumstances. In this study, we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure. We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone (GH) and cortisol did not have any effect on the secretion of these hormones. However, if a preconditioning was performed with sumatriptan, a 5-HT(1B/1D) agonist that stimulates GH and inhibits cortisol secretion, a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration, although opposite verbal suggestions were given. These findings indicate that verbally induced expectations have no effect on hormonal secretion, whereas they affect pain and motor performance. This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved, whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play, even though a conditioning procedure is performed.
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PMID:Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. 1276 20

Despite the increasing research on placebos in recent times, little is known about the nocebo effect, a phenomenon that is opposite to the placebo effect and whereby expectations of symptom worsening play a crucial role. By studying experimental ischemic arm pain in healthy volunteers and by using a neuropharmacological approach, we found that verbally induced nocebo hyperalgesia was associated to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, as assessed by means of adrenocorticotropic hormone and cortisol plasma concentrations. Both nocebo hyperalgesia and HPA hyperactivity were antagonized by the benzodiazepine diazepam, suggesting that anxiety played a major role in these effects. The administration of the mixed cholecystokinin (CCK) type-A/B receptor antagonist proglumide blocked nocebo hyperalgesia completely but had no effect on HPA hyperactivity, which suggests a specific involvement of CCK in the hyperalgesic but not in the anxiety component of the nocebo effect. Importantly, both diazepam and proglumide did not show analgesic properties on basal pain, because they acted only on the nocebo-induced pain increase. These data indicate a close relationship between anxiety and nocebo hyperalgesia, in which the CCKergic systems play a key role in anxiety-induced hyperalgesia. These results, together with previous findings showing that placebo analgesia is mediated by endogenous opioids, suggest that the analgesic placebo/hyperalgesic nocebo phenomenon may involve the opposite activation of endogenous opioidergic and CCKergic systems.
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PMID:The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. 1710 75

beta-Endorphin (BEP) has been implicated in the analgesic response to transcutaneous electrical nerve stimulation (TENS). The anterior pituitary gland is a source of beta-endorphin which shares the prohormone proopiomelanocortin (POMC) with adrenocorticotropin (ACTH). Current theory proposes that the stimulation-induced breakdown of POMC results in ACTH release with a subsequent elevation in blood cortisol levels. The purpose of this study was to determine the potential application and mechanism of TENS as an anti-inflammatory agent. Eight female subjects received low frequency, 300 musec pulse width TENS at four sites associated with relief of upper arm pain once when pain free and again while experiencing delayed onset muscle soreness (DOMS) of the elbow flexor muscle group. Blood samples were withdrawn 15 and 1 minute before and 1, 20, and 40 minutes after treatment. Serum was analyzed for cortisol by radioimmunoassay. TENS treatment failed to elevate serum cortisol concentration, but there was a significant reduction in perception of pain (p < 0.05) and an improvement in range of elbow extension (p < 0.05) when subjects were treated for DOMS. These results suggest that the anterior pituitary is not a source of BEP in TENS-induced analgesia. J Orthop Sports Phys Ther 1989;11(3):100-103.
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PMID:Influence of transcutaneous electrical nerve stimulation on pain, range of motion, and serum cortisol concentration in females experiencing delayed onset muscle soreness. 1879 21

Pain is a negative emotional experience that is modulated by a variety of psychological factors through different inhibitory systems. For example, endogenous opioids and cannabinoids have been found to be involved in stress and placebo analgesia. Here we show that when the meaning of the pain experience is changed from negative to positive through verbal suggestions, the opioid and cannabinoid systems are co-activated and these, in turn, increase pain tolerance. We induced ischemic arm pain in healthy volunteers, who had to tolerate the pain as long as possible. One group was informed about the aversive nature of the task, as done in any pain study. Conversely, a second group was told that the ischemia would be beneficial to the muscles, thus emphasizing the usefulness of the pain endurance task. We found that in the second group pain tolerance was significantly higher compared to the first one, and that this effect was partially blocked by the opioid antagonist naltrexone alone and by the cannabinoid antagonist rimonabant alone. However, the combined administration of naltrexone and rimonabant antagonized the increased tolerance completely. Our results indicate that a positive approach to pain reduces the global pain experience through the co-activation of the opioid and cannabinoid systems. These findings may have a profound impact on clinical practice. For example, postoperative pain, which means healing, can be perceived as less unpleasant than cancer pain, which means death. Therefore, the behavioral and/or pharmacological manipulation of the meaning of pain can represent an effective approach to pain management.
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PMID:Pain as a reward: changing the meaning of pain from negative to positive co-activates opioid and cannabinoid systems. 2333 53


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