Central pain after pontine infarction is associated with changes in opioid receptor binding: a PET study with 11C-diprenorphine.
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Using 18F-fluorodeoxyglucose and 11C-diprenorphine positron emission tomography (PET), we investigated alterations in glucose metabolism and opioid receptor binding in a patient with central poststroke pain, which developed after a small pontine hemorrhagic infarction. In comparison with normal databases, reduced 11C-diprenorphine binding was more accentuated than the hypometabolism on the lateral cortical surface contralateral to the symptoms, and a differential abnormal distribution between the tracers was seen in pain-related central structures. These results show that 11C-diprenorphine PET provides unique information for the understanding of central poststroke pain. (+info)
Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats.
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Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. We attempted to identify the subtype of alpha-adrenergic receptor (alpha-AR) that is responsible for the sympathetic (adrenergic) dependency of neuropathic pain in the segmental spinal injury (SSI) model in the Lewis strain of rat. This model was chosen because our previous study showed that pain behaviors in this condition are particularly sensitive to systemic injection of phentolamine (PTL), a general alpha-AR blocker. We examined the effects of specific alpha1- and alpha2-AR blockers on 1) behavioral signs of mechanical allodynia, 2) ectopic discharges recorded in the in vivo condition, and 3) ectopic discharges recorded in an in vitro setup. One week after tight ligation of the L5 and L6 spinal nerves, mechanical thresholds of the paw for foot withdrawals were drastically lowered; we interpreted this change as a sign of mechanical allodynia. Signs of mechanical allodynia were significantly relieved by a systemic injection of PTL (a mixed alpha1- and alpha2-AR antagonist) or terazosin (TRZ, an alpha1-AR antagonist) but not by various alpha2-AR antagonists (idazoxan, rauwolscine, or yohimbine), suggesting that the alpha1-AR is in part the mediator of the signs of mechanical allodynia. Ongoing ectopic discharges were recorded from injured afferents in fascicles of the L5 dorsal root of the neuropathic rat with an in vivo recording setup. Ongoing discharge rate was significantly reduced after intraperitoneal injection of PTL or TRZ but not by idazoxan. In addition, by using an in vitro recording setup, spontaneous activity was recorded from teased dorsal root fibers in a segment in which the spinal nerve was previously ligated. Application of epinephrine to the perfusion bath enhanced ongoing discharges. This evoked activity was blocked by pretreatment with TRZ but not with idazoxan. This study demonstrated that both behavioral signs of mechanical allodynia and ectopic discharges of injured afferents in the Lewis neuropathic rat are in part mediated by mechanisms involving alpha1-ARs. These results suggest that the sympathetic dependency of neuropathic pain in the Lewis strain of the rat is mediated by the alpha1 subtype of AR. (+info)
The effects of the hypothalamus on hemodynamic changes elicited by vagal nerve stimulation.
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To investigate the means by which neurogenic shock or syncope occur in dentistry, we determined the hemodynamic response to the activation of vagal tone in cats while they were under emotional stress. The hypothalamus and the vagal nerve were electrically stimulated to produce emotional stress and to activate vagal tone, respectively. Hemodynamic changes were recorded during vagal stimulation (Va group) and during vagal stimulation preceded by hypothalamic stimulation (AH + Va group). Although blood pressure decreased in both groups, the degree of hypotensive response in the AH + Va group was greater than the response in the Va group. Total peripheral resistance (TPR) was reduced in the AH + Va group but was increased in the Va group. The blood flow to the skeletal muscles in the AH + Va group was greater than that of the Va group. Reduced TPR, which could be due to vasodilation in the skeletal muscles, was the cause of intensified hypotension in the AH + Va group. Clearly, the hypotension produced by vagal stimulation was worsened when it was preceded by hypothalamic stimulation; this occurrence could be related to the tendency of blood to flow to the skeletal muscles. (+info)
The prevalence and associated features of chronic widespread pain in the community using the 'Manchester' definition of chronic widespread pain.
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OBJECTIVE: We examine the descriptive epidemiology of chronic widespread pain using the 'Manchester' definition [CWP(M)] and assess psychosocial and other features which characterize subjects with such pain according to these more stringent criteria. METHODS: A population postal survey of 3004 subjects was conducted in the Greater Manchester area of the UK. RESULTS: The point prevalence of Manchester-defined chronic widespread pain was 4.7%. CWP(M) was associated with psychological disturbance [risk ratio (RR) = 2.2, 95% confidence interval (CI) (1.4-3.5)], fatigue [RR = 3.8, 95% CI (2.3-6.1)], low levels of self-care [RR = 2.2, 95% CI (1.4-3.6)] and with the reporting of other somatic symptoms [RR = 2.0, 95% CI (1.3-3.1)]. Hypochondriacal beliefs and a preoccupation with bodily symptoms were also associated with the presence of CWP(M). CONCLUSION: This definition of chronic widespread pain is more precise in identifying subjects with truly widespread pain and its associated adverse psychosocial factors. Clear associations with other 'non-pain' somatic symptoms were identified, which further supports the hypothesis that chronic widespread pain is one feature of somatization. (+info)
Pharmacokinetics of morphine and its glucuronides following intravenous administration of morphine in patients undergoing continuous ambulatory peritoneal dialysis.
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BACKGROUND: Conjugation with glucuronic acid represents the major route of biotransformation of morphine. The glucuronides morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are eliminated via the kidneys. Therefore, chronic renal failure should affect the disposition of M3G and M6G. Numerous patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD) require pain treatment with morphine. There are only limited data available about the disposition of morphine and its active metabolites M6G and M3G in patients on CAPD. We therefore investigated the pharmacokinetics of morphine and its metabolites in CAPD patients. METHODS: This was a single intravenous dose pharmacokinetic study in 10 CAPD patients (1 female, 9 male, age 31-69 years). Morphine-hydrochloride (Mo) (10 mg) was administered intravenously. Serum, urine, and dialysate samples were collected during 24 h. GC-MS-MS and HPLC-MS methods were used to quantify respectively morphine and morphine glucuronides. RESULTS: While systemic clearance of morphine (1246+/-240 ml/min) was in the range observed in patients with normal kidney function, both M3G and M6G showed substantial accumulation. The area under the concentration-time curve (AUC) ratio of M3G:Mo (33.4+/-7.1) and of M6G:Mo (12.2+/-3.2) was 5.5 and 13.5 times higher than in patients with normal kidney function. Renal clearances of morphine, M3G, and M6G (morphine 3.0+/-2.5 ml/min; M3G 3.9+/-2.2 ml/min; M6G 3.6+/-2.2 ml/min) and dialysate clearances (morphine 4.1+/-1.3 ml/min; M3G 3.2+/-0.7 ml/min; M6G 3.0+/-0.8 ml/min) were extremely low. Therefore the accumulation of M6G and M3G is readily explained by kidney failure which is not compensated by CAPD. CONCLUSION: Accumulation of M3G and M6G is due to the substantially lowered clearance by residual renal function and peritoneal dialysis. In view of the accumulation of potential active metabolites, subsequent investigations have to assess the frequency of side-effects in patients on CAPD. (+info)
Intermittent compression units for severe post-phlebitic syndrome: a randomized crossover study.
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BACKGROUND: Although uncommon, severe post-phlebitic syndrome may be associated with persistent, intractable pain and swelling that interfere with work and leisure activities. This study was performed to determine whether intermittent compression therapy with an extremity pump benefits patients with this condition and, if so, whether the benefit is sustained. METHODS: The study was a randomized crossover trial. Over the period 1990 to 1996, all patients in the clinical thromboembolism program of an Ontario teaching hospital who had a history of deep vein thrombosis and intractable symptoms of post-phlebitic syndrome were recruited into the study. The study involved using an extremity pump twice daily for a total of 2 months (20 minutes per session). The patients were randomly assigned to use either a therapeutic pressure (50 mm Hg) or a placebo pressure (15 mm Hg) for the first month. For the second month, the patients used the other pressure. A questionnaire assessing symptoms and functional status served as the primary outcome measure and was administered at the end of each 1-month period. A symptom score was derived by summing the scores for individual questions. At the end of the 2-month study, patients were asked to indicate their treatment preference and to rate the importance of the difference between the 12 pressures. Treatment was considered successful if the patient preferred the therapeutic pressure and stated that he or she would continue using the extremity pump and that the difference between the therapeutic and placebo pressures was of at least slight importance. All other combinations of responses were considered to represent treatment failure. Patients whose treatment was classified as successful were offered the opportunity to keep the pump and to alter pressure, frequency and duration of pump use to optimize symptom management. In July 1996 the authors contacted all study participants whose treatment had been classified as successful to determine whether they were still using the pump and, if so, whether they were still deriving benefit. RESULTS: In total 15 consecutive patients (12 women and 3 men) were enrolled in the study. The symptom scores were significantly better with the therapeutic pressure (mean 16.5) than with the placebo pressure (mean 14.4) (paired t-test, p = 0.007). The treatment for 12 of the patients (80%, 95% confidence interval 52% to 96%) was considered successful. Of these, 9 patients continued to use the pump beyond the crossover study and to derive benefit. INTERPRETATION: The authors conclude that a trial of pump therapy is worthwhile for patients with severe post-phlebitic syndrome and that a sustained beneficial response can be expected in most such patients. (+info)
A patient-derived disease activity score can substitute for a physician-derived disease activity score in clinical research.
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OBJECTIVE: Joint counts have a central role in assessing disease activity in rheumatoid arthritis (RA). They are usually undertaken by physicians or nurses. We investigated whether joint counts can be devolved to patients and evaluated the use of a patient-derived Disease Activity Score (DAS). METHODS: One hundred RA patients attending a specialist unit were evaluated, comparing joint counts by a physician with patient-assessed joint counts and DAS derived from both methods. They were related to other measures of disease activity in the European League Against Rheumatism (EULAR) core data set and with the Rheumatoid Arthritis Disease Activity Index (RADAI; a validated patient self-assessment index). RESULTS: Regression analysis showed no significant differences between a physician's and patient's joint counts and DAS. There were middle to high correlations between patient and physician assessments of tender joints and swollen joints; using R2, this explained 70% of the variance for tender joints and 40% for swollen joints. Kappa analysis showed good agreement between physician and patient assessments of individual joint tenderness (kappa values 0.49-0.84). There was lower agreement for individual swollen joints (kappa values 0.02-0.61). Physician DAS and patient DAS had a similar correlation with the Health Assessment Questionnaire (HAQ) (r = 0.50 and r = 0.48, respectively). CONCLUSION: The agreements between physician and patient assessments are sufficient to allow patients' assessments to be used for clinical research. This is especially the case with a patient-derived DAS. However, the results are not directly interchangeable and further studies are needed before patients' assessments are used to guide clinical practice. (+info)
The influence of a partially HLA-matched blood transfusion on the disease activity of rheumatoid arthritis.
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OBJECTIVE: Based on the immunosuppressive effects of blood transfusions in organ transplantation, we determined the effect of a blood transfusion on disease activity of rheumatoid arthritis (RA). METHOD: In this double-blind pilot study, 40 patients with active RA were randomly assigned to receive a HLA-DRB1-matched blood transfusion (n = 30) or placebo (n = 10). Disease activity was scored according to the American College of Rheumatology response criteria during 6 months of follow-up. RESULTS: After 1 month and 6 months, respectively, 6 and 16% of patients fulfilled the response criteria in the blood transfusion group compared to none and 30%, respectively, in the placebo group. Following correction for the increase in haemoglobin levels, a majority of the response parameters in the blood transfusion group showed significant improvement compared to the placebo group. CONCLUSION: A DRB1-matched blood transfusion shows improvement of symptoms in several RA patients. Additional studies are required to identify blood transfusion regimens that enhance the potential for therapeutic responses. (+info)