Patients treated with long-term spinal infusion of high doses of morphine develop a granuloma at the location of the catheter tip. Diagnosis is based on a steady increase in intrathecal morphine dosage after a relatively prolonged period of stability, on the gradual development of neurologic signs and symptoms suggesting radicular or spinal cord compression, and on magnetic resonance images. We describe a man with central neuropathic pain after removal of a tumor. The presence of all 3 of the aforementioned diagnostic criteria led to suspicion of a spinal granuloma.

In a double-blind, placebo-controlled, cross-over trial, clonidine eliminated objective signs and subjective symptoms of opiate withdrawal for 240--360 min in eleven addicts in a hospital setting. In an open pilot study of the effects of clonidine on longer-term opiate abstinence and symptoms, the same patients did well while taking clonidine for one week. There was only one documented instance of heroin use, in a patient who did not take clonidine after hospital discharge. 6 weeks or more after the study, four patients were back on reduced doses of methadone, one was on tricyclic antidepressants, and seven were off of all opiates. All eleven patients were doing well. These data suggest that opiate withdrawal is due to increased neuronal activity in areas such as the locus coeruleus which are regulated by both alpha-2 adrenergic and opiate receptors.

The authors examined the effect of clonidine, a preferential alpha 2-adrenergic agonist, upon narcotic requirements, hemodynamics, and adrenergic responses during the perioperative period in patients undergoing CABG surgery. Anesthesia was provided by sufentanil supplemented with isoflurane; sodium nitroprusside was given as needed for hemodynamic control. Ten patients received oral clonidine preoperatively at the time of premedication, and again intraoperatively by nasogastric tube. Another group of ten untreated patients were otherwise managed identically. Intergroup differences in required anesthetic and vasoactive drug doses and recovery times were measured and evaluated, as well as hemodynamics and plasma catecholamines prior to induction, after intubation, and at intervals intra- and postoperatively. Patients who received clonidine required less diazepam prior to induction, and received 40% less sufentanil during the anesthetic period, than did untreated controls. More control patients required the addition of isoflurane to prevent hypertension. Mean blood pressures and heart rates were elevated at many sampling points in patients not treated with clonidine. Four of the clonidine-treated group required atropine for treatment of bradycardia in the pre-incision period. Plasma catecholamines were significantly lower throughout most of the study period in patients treated with clonidine. After cardiopulmonary bypass and postoperatively, cardiac outputs were significantly higher in the treated group. Patients who had received clonidine were extubated significantly earlier, and fewer of them shivered postoperatively. We conclude that perioperative treatment with clonidine reduced narcotic and anesthetic requirements, improved hemodynamics, reduced plasma catecholamines, and shortened the period of postoperative ventilation in patients undergoing coronary artery surgery.

Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal alpha 2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or with therapy-limiting side effects from opioids were randomized to receive, in a double-blind manner, 30 micrograms/h epidural clonidine or placebo for 14 days, together with rescue epidural morphine. Pain was assessed by visual analog score (VAS), McGill Pain Questionnaire, and daily epidural morphine use. Success was defined as a decrease in either morphine use of VAS pain, with the alternative variable either decreasing or remaining constant. Blood pressure, heart rate, and degree of nausea and sedation were monitored. Successful analgesia was more common with epidural clonidine (45%) than with placebo (21%). This was particularly prominent in those with neuropathic pain (56% vs. 5%). Pain scores were lower at the end of the treatment period in patients with neuropathic pain treated with clonidine rather than placebo, whereas morphine use was unaffected. Clonidine, but not placebo, decreased blood pressure and heart rate. Hypotension was considered a serious complication in 2 patients receiving clonidine and in 1 patient receiving placebo. This study confirms the findings from previous animal studies which showed the effective, potent analgesic properties of intraspinal alpha 2-adrenergic agonists and suggests that epidural clonidine may provide effective relief for intractable cancer pain, particular of the neuropathic type.

This article aims to review research in nonhuman primates demonstrating that norepinephrine can enhance the cognitive functioning of the prefrontal cortex through actions at alpha 2 A-adrenergic receptors postjunctional to noradrenergic terminals. As prefrontal cortex cognitive deficits are prominent in several psychiatric disorders, including attention-deficit hyperactivity disorder, these basic findings may have relevance for the development of novel pharmacotherapies.

BACKGROUND: Antihypertensive drugs may differ in their ability to reduce LV mass. Covariates other than drug selection, such as pretreatment LV mass, body weight, the magnitude of blood pressure reduction, race, and age may modify the response of LV mass to therapy. METHODS AND RESULTS: Patients with mild to moderate hypertension (diastolic blood pressure, 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Patients achieving the goal diastolic blood pressure of <90 mm Hg during drug titration entered a 1-year maintenance period. Longitudinal analysis examined changes from baseline echocardiogram in LV mass at 8 weeks and at 1 year, statistically adjusted for pretreatment LV mass, systolic blood pressure, body weight, sodium excretion, physical activity, race, and age. Significant reductions at 1 year in adjusted LV mass were seen for patients in the highest tertile of pretreatment LV mass treated with hydrochlorothiazide (mean,-42.9; 95% confidence limits,-65.5,-20.2 g), captopril (mean,-38.7; 95% confidence limits,-61.0,-16.4 g), and atenolol (mean,-28.1; 95% confidence limits,-50.9,-5.3 g). These treatment effects differed from those of prazosin, diltiazem, or clonidine. CONCLUSIONS: Antihypertensive drugs have disparate effects on LV mass independent of the magnitude of blood pressure reduction. Patients with adequate blood pressure control on captopril, hydrochlorothiazide, and atenolol show a reduction of LV mass after 1 year of treatment, whereas patients on diltiazem, clonidine, or prazosin do not.

This symposium is concerned with the treatment of spasticity and, in particular, with results from studies of tizanidine as a treatment for patients with MS and spinal cord injury. In this article, the definitions and pathophysiologies of spasticity are reviewed, and the issue of when and if to treat spasticity is evaluated. The merits of newer pharmacologic and invasive therapies are discussed relative to reduction of patient discomfort and the possibility of restored function.

PURPOSE: To investigate the effects of alpha(2)-adrenergic agonists on perioperative mortality and cardiovascular complications in adults undergoing surgery. METHODS: MEDLINE (1966 to May 2002), EMBASE (1980 to May 2002), the Cochrane Clinical Trials Register, the Science Citation Index, and bibliographies of included articles were searched without language restriction. Randomized trials comparing preoperative, intraoperative, or postoperative (first 48 hours) administration of clonidine, dexmedetomidine, or mivazerol with controls were included. Studies had to report any of the following outcomes: mortality, myocardial infarction, ischemia, or supraventricular tachyarrhythmia. Treatment effects were calculated using the fixed-effects model. Heterogeneity was assessed using the Q test. RESULTS: Twenty-three trials comprising 3395 patients were included. Overall, alpha(2)-adrenergic agonists reduced mortality (relative risk [RR]= 0.64; 95% confidence interval [CI]: 0.42 to 0.99; P = 0.05) and ischemia (RR = 0.76; 95% CI: 0.63 to 0.91; P = 0.003) significantly. They also reduced mortality (RR = 0.47; 95% CI: 0.25 to 0.90; P = 0.02) and myocardial infarction (RR = 0.66; 95% CI: 0.46 to 0.94; P = 0.02) during vascular surgery. During cardiac surgery, alpha(2)-adrenergic agonists reduced ischemia (RR = 0.71; 95% CI: 0.54 to 0.92; P = 0.01) and were associated with trends toward lower mortality (RR = 0.49; 95% CI: 0.12 to 1.98; P = 0.3) and a reduced risk of myocardial infarction (RR = 0.83; 95% CI: 0.35 to 1.96; P = 0.7). CONCLUSION: Alpha-2 adrenergic agonists reduce mortality and myocardial infarction following vascular surgery. During cardiac surgery, they reduce ischemia and may also have effects on mortality and myocardial infarction. Large randomized trials are needed to evaluate these agents during cardiac and vascular surgery.

Hot flashes are the most common symptom of the climacteric, although prevalence estimates are lower in some rural and non-Western areas. The symptoms are characteristic of a heat-dissipation response and consist of sweating on the face, neck, and chest, as well as peripheral vasodilation. Although hot flashes clearly accompany the estrogen withdrawal at menopause, estrogen alone is not responsible since levels do not differ between symptomatic and asymptomatic women. Until recently it was thought that hot flashes were triggered by a sudden, downward resetting of the hypothalamic setpoint, since there was no evidence of increased core body temperature. Evidence obtained using a rapidly responding ingested telemetry pill indicates that the thermoneutral zone, within which sweating, peripheral vasodilation, and shivering do not occur, is virtually nonexistent in symptomatic women but normal (about 0.4 degrees C) in asymptomatic women. The results suggest that small temperature elevations preceding hot flashes acting within a reduced thermoneutral zone constitute the triggering mechanism. Central sympathetic activation is also elevated in symptomatic women which, in animal studies, reduces the thermoneutral zone. Clonidine reduces central sympathetic activation, widens the thermoneutral zone, and ameliorates hot flashes. Estrogen virtually eliminates hot flashes but its mechanism of action is not known.