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

The purpose of this study was to investigate strain-related differences in the onset and maintenance of thermal hyperalgesia following the induction of peripheral nerve injury in two inbred strains of rats (Fischer 344 and Lewis) and two outbred strains of rats (Sprague-Dawley and Wistar). Neuropathic pain was induced via unilateral ligation of the left sciatic nerve with chromic gut sutures. A plantar analgesia meter was used to measure paw-withdrawal latency from the ligated vs. unligated hind paws of inbred vs. outbred strains of rats to investigate strain-related differences in nerve injury-induced thermal hyperalgesia. The results demonstrated no significant effects of animal strain on presurgical paw-withdrawal latency values. Following the sciatic nerve ligation (SNL) surgery, a significant hyperalgesic response was elicited from the Sprague-Dawley and Wistar rats (outbred strains) for at least 28 days. Conversely, data analyses from the inbred strains failed to demonstrate significant hyperalgesic responses to peripheral nerve injury, with the exception of postsurgical day 10. These data emphasize the importance of considering the strain of the rat being investigated before extrapolating the results from animals experiments to treatment strategies for humans with chronic neuropathic pain.
 ...
PMID:Strain differences in neuropathic hyperalgesia. 1063 47

Several methods are available to measure splanchnic blood flow and gut ischaemia. Tonometry is most practical for peri-operative use. Epidural blockade from T5 to T11 causes mesenteric arteriovenous vasodilation and may increase splanchnic blood flow. This study assesses the ability of tonometry to measure differential effects of opiate and epidural analgesia on splanchnic blood flow. Forty patients for elective colorectal surgery were randomly allocated to receive epidural infusion or intravenous morphine. Gastric mucosal PCO2, pHi, standard pHi, PCO2 gap and pH gap were measured after induction and on termination of surgery. These parameters were within normal limits at the end in most cases and there was no significant difference between the groups. The complication rate was similar in both groups and was not correlated with low pHi, but was correlated with blood loss. We were unable to demonstrate a difference in splanchnic perfusion, as assessed by gastric tonometry, between the two groups.
 ...
PMID:A comparison of opiate- and epidural-induced alterations in splanchnic blood flow using intra-operative gastric tonometry. 1112 54

Anaesthesia and surgical procedures lead to a reduction of intestinal motility, and opioids may produce a postoperative ileus, that might delay postoperative feeding. The aim of this prospective randomised study is to test whether or not different kinds of epidural analgesia (Group A: morphine 0.0017 mg/kg/h and bupivacaine 0.125%-0.058 mg/kg/h; Group B: morphine alone 0.035 mg/kg/12h in the postoperative period) allow earlier postoperative enteral feeding, enhance intestinal motility a passage of flatus and help avoid complications, such as nausea, vomiting, ileus, diarrhoea, pneumonia or other infective diseases. We included in the study 60 patients (28 males and 32 females) with a mean age of 61.2 years (range 50-70) and with an ASA score of 2 or 3. All patients had hepato-biliary-pancreatic neoplasm and were candidates for major surgery. We compared two different pharmacological approaches, i.e., morphine plus bupivacaine (30 patients, Group A) versus morphine alone (30 patients, Group B). Each medication was administered by means of a thoracic epidural catheter for the control of postoperative pain. In the postoperative course we recorded every 6 hours peristaltic activity. We also noted morbidity (pneumonia, wound sepsis) and mortality. Effective peristalsis was present in all patients in Group A within the first six postoperative hours; in Group B, after 30 hours. Six patients in Group A had bowel motions in the first postoperative day, 11 in the second day, 10 in the third day and 3 in fourth day, while in Group B none in the first day, two in the second, 7 in the third, 15 in the fourth, and 6 in the fifth: the difference between the two groups was significant (p<0.05 in 1st, 2nd, 4th and 5th days). Pneumonia occurred in 2 patients of Group A, and in 10 of Group B (p < 0.05). We conclude that epidural analgesia with morphine plus bupivacaine allowed a move rapid return to normal gut activity and early enteral nutrition compared with epidural analgesia with morphine alone.
 ...
PMID:Morphine plus bupivacaine vs. morphine peridural analgesia in abdominal surgery: the effects on postoperative course in major hepatobiliary surgery. 1097 18

Opioids are widely used analgesics in patients with advanced cancer. However, their effectiveness for pain relief is often limited by the most frequently occurring side effect, opioid bowel dysfunction (OBD). Because conventional laxation measures are often ineffective in treating OBD, alternative approaches need to be investigated. Opioid action on the gut appears to be mediated mainly by receptors in the gastrointestinal (GI) tract rather than by those in the central nervous system (CNS). Opioid antagonists, such as naloxone, naltrexone, and nalmefene, have been studied as a means of antagonizing the peripheral effects of opioids, but these agents can enter the CNS and reverse analgesia or cause opioid withdrawal symptoms. Methylnaltrexone (MNTX) is a novel quaternary derivative of naltrexone that does not cross the blood-brain barrier and acts as a selective peripheral opioid receptor antagonist. In normal volunteers, intravenous or oral MNTX reverses opioid-induced reduction in bowel motility without affecting analgesia. Bioavailability of MNTX is low after oral administration, and plasma levels do not correlate with its actions in the gut, suggesting a predominantly local luminal action of MNTX on the gut. In patients receiving long-term opioid therapy, MNTX administered intravenously or orally was effective in reducing the delay in oral-cecal transit and eliciting laxation responses in all subjects without causing withdrawal symptoms. MNTX is a peripherally selective opioid antagonist that may have clinical utility in managing OBD with minimal adverse effects.
 ...
PMID:A review of the potential role of methylnaltrexone in opioid bowel dysfunction. 1175 93

Cardiac surgery elicits a cascade of stress responses mediated by the release of various cytokines and stress hormones [Roth-Isigkeit 1998]. Apart from the stress induced by the surgical process, cardiopulmonary bypass (CPB) has been documented to play a major role in the perioperative stress response seen following cardiac surgery [Butler 1993, McBride 1995, Hall 1997]. The imbalance in pro- and anti-inflammatory responses may affect outcome in cardiac surgery patients [Casey 1993, McBride 1995, Menasch 1995]. Contact of blood with the CPB circuit, along with hypoperfusion of various organs prior to and during CPB, may aggravate this stress response and contribute to adverse outcomes in the perioperative period [Casey 1993, Menasch 1995, Tonnesen 1996]. Splanchnic hypoperfusion that occurs in cardiac surgery patients [Landow 1991] can result in increased permeability of the gut mucosal barrier, resulting in endotoxemia and release of proinflammatory cytokines. Lungs and kidneys play a role in sequestrating the proinflammatory cytokines and, in the presence of hypoperfusion, may be damaged by these cytokines [Gilliland 1999, Liebold 1999, Gormley 2000]. Avoiding CPB may reduce this stress response. Anesthetic techniques such as thoracic epidural analgesia (TEA) that improve splanchnic perfusion [Moore 1995, Kapral 1999, Ai 2001] may have a role in improving patient outcome. It is further known that ischemic myocardium can be a major source of proinflammatory cytokines [Wan 1999a]. The cardiac sympathetic block resulting from TEA has been shown to reduce ischemia reperfusion injury [Blomberg 1989, Blomberg 1990, Liem 1992a, Liem 1992b, Liem 1992c, Kirno 1994, Stenseth 1994]. Beating heart surgery done without the aid of CPB significantly attenuates cytokine and stress response [Brasil 1998, Fransen 1998, Gu 1998, Wan 1999b, Ganapathy 1999a, Ganapathy 2000a]. There is reduced renal dysfunction following beating heart surgery [Ascione 1999], which may be related to reduced proinflammatory cytokine surge. Thoracic epidural analgesia inhibits intraoperative cortisol as well as catecholamine surge but does not add further to the reduction in cytokine response [Ganapathy 1999b].
 ...
PMID:Stress and inflammatory response after beating heart surgery versus conventional bypass surgery: the role of thoracic epidural anesthesia. 1182 61

Dihydroetorphine (DHE) is one of the strongest analgesic opioid alkaloids known; it is 1000 to 12000 times more potent than morphine. Several in vitro and in vivo studies have shown that DHE is a selective mu-opioid receptor (OP(3)) agonist that also binds and activates all human recombinant mu-, delta-, and kappa-opioid receptors (OP(3), OP(1), and OP(2)). The onset of the analgesic effect of DHE in rodents is rapid, 5 to 15 min after parenteral administration; the duration of action is short, the analgesic effect disappears within 120 min after administration. By oral administration much higher doses of DHE are required to produce analgesic effects. These characteristics are accounted for by the pharmacokinetic properties of DHE in the rat, namely, by rapid distribution of DHE from the injection site to the brain and rapid metabolism by glucuronidation in the gut and liver followed by elimination into the bile. Continuous infusion and repeated administration of DHE lead to the development of tolerance to analgesia, physical dependence, and a rewarding effect in normal rats but not in animals with formalin-induced inflammation. Although formalin-induced inflammation is only one type of pain stimulus, these findings suggest that DHE addiction would be observed only in the case of pain-free conditions. Clinical reports in China show that sublingual doses of DHE, 20 to 180 microg, produce a potent analgesic effect with only mild side effects, including dizziness, somnolence, nausea, vomiting, constipation, and shortness of breath. To improve the short-lasting effect following sublingual administration, transdermal delivery of DHE via a patch has been investigated. The patch formulation of DHE produces continuous analgesic effect with minimal physical dependence and rewarding effect in rats suffering from chronic pain. This patch formulation, which is very suitable for DHE, may be viable for the treatment of severe pain and is likely to improve patients' quality of life.
 ...
PMID:Dihydroetorphine: a potent analgesic: pharmacology, toxicology, pharmacokinetics, and clinical effects. 1248 Nov 94

Opioid treatment for postoperative or chronic pain is frequently associated with adverse effects, the most common being dose-limiting and debilitating bowel dysfunction. Postoperative ileus, although attributable to surgical procedures, is often exacerbated by opioid use during and following surgery. Postoperative ileus is marked by increased inhibitory neural input, heightened inflammatory responses, decreased propulsive movements and increased fluid absorption in the gastrointestinal tract. The use of opioids for chronic pain is characterised by a constellation of symptoms including hard dry stools, straining, incomplete evacuation, bloating, abdominal distension and increased gastroesophageal reflux. The current management of opioid-induced bowel dysfunction among patients receiving opioid analgesics consists primarily of nonspecific ameliorative measures. Intensive investigations into the mode of action of opioids have characterised three opioid receptor classes -mu, delta and kappa- that mediate the myriad of peripheral and central actions of opioids. Activation of mu-opioid receptors in the gastrointestinal tract is responsible for inhibition of gut motility, whereas receptors in the central nervous system mediate the analgesic actions of opioids. Blocking peripheral opioid receptors in the gut is therefore a logical therapeutic target for managing opioid-induced bowel dysfunction. Available opioid antagonists such as naloxone are of limited use because they are readily absorbed, cross the blood-brain barrier, and act at central opioid receptors to reverse analgesia and elicit opioid withdrawal. Methylnaltrexone and alvimopan are recently developed opioid antagonists with activity that is restricted to peripheral receptors. Both have recently shown the ability to reverse opioid-induced bowel dysfunction without reversing analgesia or precipitating central nervous system withdrawal signs in non-surgical patients receiving opioids for chronic pain. In addition, recent clinical studies with alvimopan suggest that it may normalise bowel function without blocking opioid analgesia in abdominal laparotomy patients with opioid-related postoperative ileus.
 ...
PMID:Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. 1265 45

Postoperative gastro-intestinal motility disorders are of major importance for patient management following abdominal surgery both for clinical and economic reasons. In recent years, new pathophysiological links have been identified that contribute to postoperative ileus. The activation of sympathetic efferent neurons by visceral afferent nerve fibers, catecholamines, the stimulation of beta 3 -receptors in the gut wall, an inflammatory response of the gut wall with the consecutive release of nitric oxide, and opioids given for postoperative analgesia seem to be of major importance regarding the development of postoperative ileus. The pharmacological reduction of visceral afferent nerve fiber activity, non-steroidal anti-inflammatory drugs (NSAIDs) instead of opioids for postoperative pain, peripheral opioid receptor antagonists together with opioids for postoperative analgesia, motilides and 5-HT4 receptor agonists as prokinetic drugs are strategies that are currently evaluated to treat postoperative ileus. Our review summarizes the present knowledge on the pathophysiology of postoperative ileus and new experimental treatments that might be of importance in the future.
 ...
PMID:[Postoperative ileus: part I (Experimental results)]. 1270 Sep 89

The gut is a neurological organ, which implies that many neuroactive drugs such as opioid analgesics can seriously disturb gastrointestinal function, because many of the transmitters and transmitter receptors present in the brain are also found in the enteric nervous system. One of the most common manifestations of opioid-induced bowel dysfunction is constipation which results from blockade of peristalsis and intestinal fluid secretion. The discovery of opioid receptor antagonists with a peripherally restricted site of action, such as N-methylnaltrexone and alvimopan, makes it possible to normalize bowel function in opiate-treated patients without compromising central opioid analgesia. There is emerging evidence that opioid receptor antagonists may also have prokinetic actions, reversing pathological states of gastrointestinal hypomotility that are due to overactivity of the enteric opioid system.
 ...
PMID:Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. 1513 26

Opioids are associated with a number of adverse effects, constipation being the most common long-term adverse effect in patients with advanced cancer. Significant progress has been made over the past several decades in understanding the mechanisms of action of opioid compounds; however, these advances have yielded few new treatments for the bowel dysfunction caused by opioids. Methylnaltrexone, the first peripheral opioid receptor antagonist and currently under clinical investigation, has the potential to prevent or treat opioid-induced peripherally mediated side effects, such as constipation, without interfering with analgesia. This article reviews existing clinical data on methylnaltrexone, focusing on the antagonism of opioid-induced adverse effects in the gut.
 ...
PMID:Clinical status of methylnaltrexone, a new agent to prevent and manage opioid-induced side effects. 1532 15


<< Previous 1 2 3 4 5 6 7 Next >>