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)

The COX-inhibiting nitric oxide donors (CINODs) are a new class of agents designed for the treatment of pain and inflammation. CINODs have a multi-pathway mechanism of action that involves COX inhibition and nitric oxide donation. The anti-inflammatory and analgesic effects of COX inhibition are reinforced through inhibition of caspase-1 regulated cytokine production, while nitric oxide donation provides multiorgan protection. Whereas both conventional nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2-selective NSAIDs are associated with a variety of adverse effects on the renal system, such as hypertension and edema, CINODs may offer an improved renal safety profile. These agents are devoid of hypertensive effects in animal models and their mechanism of action suggests that they may not cause edema. CINODs also have other renal-sparing effects, being better tolerated than NSAIDs in models of kidney failure. CINODs have been shown to prevent platelet activation in vitro and exhibit anti-thrombotic activity in vivo. In animal models of ischemia/reperfusion, CINODs treatment results in improved recovery of heart contractility and reduced left ventricular end-diastolic pressure, in contrast to the effects of aspirin. The combination of improved analgesia, reduced gastrointestinal toxicity and cardiorenal protection has been established in animal models, and early clinical results suggest a favourable gastrointestinal safety profile in humans. The potential for CINODs to provide cardiorenal protection in humans is currently being investigated.
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PMID:COX-inhibiting nitric oxide donors (CINODs): potential benefits on cardiovascular and renal function. 1661 Oct 49

Previous in vivo studies indicate that locally injected redox-modulating agents can sensitize polymodal peripheral skin nociceptors resulting in acute changes in pain perception. Since endogenous thiol-modifying redox agents are normally present in the interstitial tissue, and could be found in higher concentration in certain conditions (e.g., tissue injury, inflammation, and ischemia), we designed this study to evaluate the peripheral nociceptive effects of locally injected endogenous-reducing cysteine analogs, L-cysteine, D-cysteine and D,L-homocysteine and endogenous-oxidizing cysteine analogs, L-cystine, D-cystine and D,L-homocystine using the acute model of thermal peripheral nociception in intact rats. We found that the reducing cysteine analogs induced potent dose- and time-dependent hyperalgesia and conversely the oxidizing cysteine analogs induced potent dose- and time-dependent analgesia. In the presence of 3betaOH, a novel neuroactive steroid and potent voltage-dependent blocker of T-type Ca2+ channels, the hyperalgesic effects of the reducing agents were diminished, whereas the analgesic effects of the oxidizing agents were enhanced strongly suggesting that the observed nociceptive effects were, at least in part, mediated via the peripheral T channels. Our findings imply that changes in the redox states of the peripheral nociceptors (favoring either reduced or oxidized forms of cysteine molecules) may function as a local intrinsic mechanism in controlling peripheral pain perception.
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PMID:Differential effects of endogenous cysteine analogs on peripheral thermal nociception in intact rats. 1678 75

Historically, the use of regional anesthetic techniques in patients with preexisting central nervous system (CNS) disorders has been considered relatively contraindicated. The fear of worsening neurologic outcome secondary to mechanical trauma, local anesthetic toxicity, or neural ischemia is commonly reported. We examined the frequency of new or progressive neurologic complications in patients with preexisting CNS disorders who subsequently underwent neuraxial blockade. The medical records of all patients at the Mayo Clinic from the period 1988 to 2000 with a history of a CNS disorder who subsequently received neuraxial anesthesia or analgesia were retrospectively reviewed. One-hundred-thirty-nine (n = 139) patients were identified for study inclusion. Mean patient age was 60 +/- 17 yr. Gender distribution was 86 (62%) males and 53 (38%) females. An established CNS disorder diagnosis was present a mean of 23 +/- 23 yr at the time of surgical anesthesia, with 74 (53%) patients reporting active neurologic symptoms. Spinal anesthesia was performed in 75 (54%) patients, epidural anesthesia or analgesia in 58 (42%) patients, continuous spinal anesthesia in 4 (3%) patients, and a combined spinal-epidural technique in 2 (1%) patients. Bupivacaine was the local anesthetic most commonly used in all techniques. Epinephrine was added to the injectate in 72 (52%) patients. There were 15 (11%) technical complications, with the unintentional elicitation of a paresthesia and traumatic needle placement occurring most frequently. A satisfactory block was reported in 136 (98%) patients. No new or worsening postoperative neurologic deficits occurred when compared to preoperative findings (0.0%; 95% confidence interval, 0.0%-0.3%). We conclude that the risks commonly associated with neuraxial anesthesia and analgesia in patients with preexisting CNS disorders may not be as frequent as once thought and that neuraxial blockade should not be considered an absolute contraindication within this patient population.
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PMID:Neuraxial anesthesia and analgesia in patients with preexisting central nervous system disorders. 1679 Jun 57

Intrathecal injection of phenol (ITP) has been used to control intractable pain and spasticity. Direct caustic nerve damage has been postulated as the mechanism of analgesia. Sensation is commonly recovered, suggesting that a spontaneous regeneration process takes place. There is, however, a lack of mechanistic information on ITP therapy. To define morphologically the neurolysis and regeneration phenomena produced by ITP, anesthetized rats were subjected to laminectomy at L5; 5 microl of 22% phenol in saline solution or vehicle (control) was injected. Light and electron microscopy studies of nerve roots were performed at 2, 14, and 60 days after injection. Rats given ITP showed at the early stage a variable amount of roots with signs of infarction characterized by loss of axon-myelin units and thrombosis of intra-root vessels. At 14 days, abundance of macrophages removing debris, open vessels, and nerve sprouts was identified in damaged roots. At this time, non-myelinating glial fibrillary acidic protein-positive Schwann cells were observed in both damaged and apparently undamaged roots. At 60 days, abundance of 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive Schwann cells myelinating newly formed axons was observed in damaged roots. Control rats did not show signs of neural or vascular pathology. Attempting to prevent thrombosis, another group of rats received heparin before ITP; these anti-coagulated rats developed radicular thrombosis, neurolysis, and hemorrhage. In conclusion, neurolysis produced by ITP is associated with acute ischemia (not prevented by heparin) and is followed by vascular, nerve, and myelin regeneration. Our results help understand the lack of efficacy of and some complications by ITP clinical therapy.
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PMID:Nerve root degeneration and regeneration by intrathecal phenol in rats: a morphologic approach. 1711 39

We present a patient who underwent pulmonary lobectomy with thoracic epidural analgesia and developed postoperative sensory-motor symptoms of the lower limbs. Radiological investigation indicated ischemia of the conus medullaris as the likely cause. The motor deficit disappeared gradually and the patient was mobilizing independently when discharged on postoperative day 21.
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PMID:Neurologic dysfunction after major thoracic surgery in a patient with severe arteriosclerotic disease receiving epidural analgesia. 1717 72

With the introduction of biomarkers like troponin I (cTnI), our ability to identify and quantify myocardial infarction in the postoperative period has been greatly enhanced. Even small elevations of cTnI should be considered as a myocardial infarction. Small increases in cTnI postoperatively have indeed been found to be associated with worse short and long-term outcomes, the higher the cTnI level the worse the outcome. Studies undertaken in the 1980s when postoperative myocardial infarction (PMI) was detected by means of electrocardiogram recordings every 12 hours following operation suggested that this complication occurred on the second or third postoperative day. More recent studies where postoperative myocardial necrosis has been detected by repeated troponin dosages have revealed that, in fact, postoperative myocardial infarction appears much earlier between 12 and 32 hour after the end of surgery. Two types of PMI were identified based on intense troponin surveillance. They stem from two different major pathophysiological mechanisms. One seems to be related to plaque-vulnerability, while the other may be due to the effects of prolonged ischemia. The postoperative period should be regarded as a vulnerable period' that acts synergistically with both plaque and patient vulnerabilities in the development of PMI. Monitoring troponin levels in the postoperative period following surgery enables the identification of patients with myocardial damage and the institution of early aggressive intervention (e.g., intensive beta blockers therapy, adequate analgesia, correction of anemia) in order to prevent the evolution of PMI during this golden period' that lasts about two days. In patients that are prone to develop PMI, and especially in those who are prone to develop PMI related to plaque rupture, prevention can be achieved by better preoperative identification of the vulnerable plaque, and by a better plaque stabilization, either metabolically (e.g., statins) or by actual coronary stenting. Further understanding of the mechanisms underlying PMI, as well as their early identification, may contribute to the reduction of the incidence of PMI and its associated morality in the future.
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PMID:Postoperative myocardial infarction: pathophysiology, new diagnostic criteria, prevention. 1723 64

The analgesic activity of clonidine, isradipine, antagosane (aprotinine), transamine, and their combinations with fentanyl in subanalgesic doses was experimentally studied on mice, by using the tail-flick test. Analgesic activity was found in clonidine, antagosane, and transamine. A combination of fentanyl used in subanalgesic doses and clonidine, isradipine, antagosane, or transamine had supertotal analgesic activity. The findings serve as a basis for effectively making up a component of analgesia during anesthetic support at surgery made in patients with baseline sympathicotonia, ischemia/reperfusion syndrome, and a systemic inflammatory reaction.
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PMID:[Experimental investigations of the analgesic activity of fentanyl and the non-opiodal agents -clonidine and isradipine, and protease inhibitors]. 1756 6

Spinal Cord Stimulation (SCS) is a treatment option for chronic pain patients. Spinal cord stimulation has been employed in the treatment of chronic pain for more than 30 years. The most common indication for SCS is the failed back syndrome with leg pain. Its indications have expanded beyond back and lower extremities pain to include axial low back pain, CRPS, mesenteric ischemia, peripheral neuropathy, limb ischemia, and refractory angina pectoris. The SCS has become a more versatile form of analgesia. The number of wound complications will surely rise in conjunction with the increasing number of devices being implanted. We describe a case of a well-differentiated squamous cell carcinoma occurring within the incision site of a recently implanted spinal cord stimulator early in the postoperative period. The patient developed a rapidly growing mass within the leads incision. The mass was confirmed to be squamous cell carcinoma by biopsy. The mass was excised under local anesthesia with appropriate margins. It was determined that the carcinoma did not extend below the dermis, and that there was no involvement of the underlying fascia. The device was tested for proper functioning, and the leads were thus left in place. While the development of skin malignancies in surgical wounds has been described in the literature, to our knowledge there have been no reports of a cutaneous neoplasm developing early in the postoperative period after spinal cord stimulator implantation.
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PMID:Squamous cell carcinoma occurring within incision of recently implanted spinal cord stimulator. 1798

With limited resources, cardiac surgery is frequently cancelled due to lack of ICU beds. Immediate postoperative extubation (UFT) is performed in our hospital setting. The aim of the present study is to report patients undergoing off-pump aortocoronary bypass grafting (OPCABG) with immediate extubation and no ICU stay. Eighty-five patients undergoing OPCABG were included. UFT analgesia consisted of high thoracic epidural analgesia (n=65), or PCA morphine (n=20). Discharge criteria from PACU to cardiac ward were: alert, cooperative patient, respiratory rate <25/min, PaO(2)>80 mmHg and PaCO(2)<45 mmHg, temperature >36 degrees C, hemodynamic stability, no bleeding, no ischemia, and sufficient analgesia. More males (71/14) were included. Mean age was 63.4 years, NYHA class III, ejection fraction 59.4. Three grafts were performed in 119 min. Patients were extubated 12+/-2 min after closure. After 428 min in PACU, four patients did not meet ward criteria; three bradycardia requiring pacing, one elevated CK-MB. Two patients returned to the ICU, one for hypertension, and one for hypovolemia. Cardiac complications were: atrial fibrillation (29%), MI=2, bradycardia=3. During the same period, 304 OR-extubated patients spent 21+/-6 h in the ICU. The cost from leaving the OR until the patient reached the cardiac ward was 1265$ for ICU bypass patients vs. 6405$ for ICU patients, the difference representing 5140$ per patient. ICU bypass after OPCABG is safe. By avoiding ICU, this protocol reduces costs, improves resource utilization and may reduce OR cancellation due to ICU bed shortages.
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PMID:Do patients after off-pump coronary artery bypass grafting need the intensive care unit? A prospective audit of 85 patients. 1802 92

Postoperative pain can intensify the sympathoadrenergic reaction, which is commonly seen after surgery, and thus possibly pave the way for certain complications, such as coronary ischemia, bronchopneumonia, intestinal stasis, thromboembolism, infection, sepsis, and metabolic disturbances. Investigations of cardiovascular, respiratory, gastrointestinal, metabolic, and immunologic function indicate that high-quality pain relief can diminish postoperative organ impairment and failure. Some aspects of the improvements attributed to the quality of analgesia, such as prevention of tachycardia and hypertension, attenuation of hyperglycemia and catabolism, improvement of gastrointestinal motility and cellular immunity cannot be definitely distinguished from the effects of sympathetic blockade due to epidural analgesia with local anesthetics, however. There is another aspect of the problem. The better the quality of postoperative pain relief, the more likely it is that analgesia-related complications, such as respiratory depression (opioids), cardiovascular depression (epidural local anesthetics), renal failure (NSAIDs) and bladder dysfunction (epidural opioids and local anesthetics) will occur. The question of whether postoperative morbidity and mortality can be reduced by effective analgesia has been investigated in the past few years. Some studies indicate that better analgesia is advantageous for the patient, especially with respect to postoperative complications, hospital stay, long-term well being, and costs. In other clinical trials incorporating more patients, however, this hypothesis had to be rejected. At present, therefore, we cannot state that effective pain relief influences postoperative morbidity and mortality.
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PMID:[Influence of postoperative pain on morbidity and mortality.]. 1841 28


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