Objective. To determine whether delayed infusion of COX1/COX2 inhibitors (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress ongoing sensitization in central trigeminovascular neurons in t...Objective. To determine whether delayed infusion of COX1/COX2 inhibitors (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress ongoing sensitization in central trigeminovascular neurons in the rat. Background. The majority of migraineurs seeking secondary or tertiary medical care develop cutaneous allodynia during the course of migraine, a sensory abnormality mediated by sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain free within a narrow window of time (20 to 120 minutes) that opens with the onset of pain and closes with the establishment of central sensitization. Can drugs that tackle ongoing central sensitization render allodynic migraineurs pain free after the window for triptan therapy has expired? Methods. Patients exhibiting migraine with allodynia were divided in two groups (n=14, each): group 1 received delayed sumatriptan injection (6 mg) 4 hours after onset of attack-which failed to render them pain free-and ketorolac infusion (two 15 mg boluses) 2 hours later; group 2 received delayed ketorolac monotherapy 4 hours after onset of attack. Pain intensity (visual analog scale) and skin sensitivity (quantitative sensory testing) were measured when the patients were migraine free (baseline); 4 hours after onset of migraine (just before treatment); 2 hours after sumatriptan; 1 hour after ketorolac. In the rat, we tested whether infusion of ketorolac (0.4 mg/kg) or indomethacin (1 mg/kg) will block ongoing sensitization in peripheral and central trigeminovascular neurons. The induction of sensitization (using topical application of inflammatory soup on the dura)and its suppression by COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity and responses to mechanical and thermal stimuli. Results. Patients had normal skin sensitivity in the absence of migraine, and presented cutaneous allodynia 4 hours after onset of migraine. In group 1, all patients continued to exhibit allodynia 2 hours after sumatriptan treatment, and none of them became pain free. However, 71%and 64%of the patients in groups 1 and 2, respectively, were rendered free of pain and allodynia within 60 minutes of ketorolac infusion. Nonresponders from both groups, in contrast to the responders, had had a history of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked sensitization in meningeal nociceptors and suppressed ongoing sensitization in spinal trigeminovascular neurons. This inhibitory action was reflected by normalization of neuronal firing rate and attenuation of neuronal responsiveness to mechanical stimulation of the dura, as well as mechanical and thermal stimulation of the skin. Conclusions. The termination of migraine with ongoing allodynia using COX1/COX2 inhibitors is achieved through the suppression of central sensitization. Although parenteral administration of COX1/COX2 inhibitors is impractical as routine migraine therapy, it should be the rescue therapy of choice for patients seeking emergency care for migraine. These patients should never be treated with opioids, particularly if they had no prior opioid exposure.展开更多
Background and aims: Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain, suggesting the presence of hyperalgesia. It is unclear whether this reflects activation...Background and aims: Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain, suggesting the presence of hyperalgesia. It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations. In the former case, hyperalgesia should occur when intensity of non-painful sensations is still low. The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways. Methods: Forty eight consecutive dyspeptic patients (35 female) underwent gastric sensitivity testing with a barostat balloon using a double random staircase protocol. At the end of every distending step, patients scored perception of upper abdominal sensations on a graphic 0-6 rating scale and completed visual analogue scales (VAS 0-100 mm) for pain, nausea, satiety, and fullness. The end point was a rating scale of 5 or more. Results: Hypersensitivity was present in 20 patients (40%); gastric compliance did not differ between normo-and hypersensitive patients. At maximal distension (score 5 or more), hypersensitive patients had significantly lower distending pressures and intra-balloon volumes, but similar VAS scores for pain, nausea, satiety, and fullness compared with normosensitive patients. In both normosensitive and hypersensitive patients, elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea, satiety, and fullness. Conclusions: Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures. Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations. These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity.展开更多
An increasing incidence of allergic bronchopulmonary aspergillosis (ABPA) as a complication in patients with cystic fibrosis (CF) is reported. The objective of this retrospective case-control study was to assess poten...An increasing incidence of allergic bronchopulmonary aspergillosis (ABPA) as a complication in patients with cystic fibrosis (CF) is reported. The objective of this retrospective case-control study was to assess potential risk factors for ABPA and for Aspergillus fumigatus sensitisation (AFS). In a group of 160 CF patients, 11 (7% ) fulfilled the diagnostic criteria for ABPA and 20 (13% ) had evidence of AFS. They were compared to 62 control CF patients (25 for ABPA and 37 for AFS group) without evidence of ABPA or AFS using extended matching for sex, age and weight. AFS patients had received significantly higher cumulative doses of inhaled corticosteroids than their respective controls (OR 8.0; 95% CI 1.74-63). Bronchial colonisation with Stenotropho monasmaltophilia was strongly and independently associated with ABPA (OR 20; 95% CI 2.8-infinity). A longer duration of Pseudomonas aeruginosa colonisation was independently associated with AFS (OR per year 1.50; 95% CI 1.12-infinity). Conclusion: Cystic fibrosis patients with allergic bronchopulmonary aspergillosis have a more frequent isolation of S. maltophilia in their sputum than their controls. Longer duration of colonisation with P. aeruginosa is a risk factor for Aspergillus fumigatus sensitisation. Higher cumulative doses of inhaled corticosteroids are associated with Aspergillus fumigatus sensitisation and their role as a risk factor needs to be clarified.展开更多
文摘Objective. To determine whether delayed infusion of COX1/COX2 inhibitors (ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress ongoing sensitization in central trigeminovascular neurons in the rat. Background. The majority of migraineurs seeking secondary or tertiary medical care develop cutaneous allodynia during the course of migraine, a sensory abnormality mediated by sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain free within a narrow window of time (20 to 120 minutes) that opens with the onset of pain and closes with the establishment of central sensitization. Can drugs that tackle ongoing central sensitization render allodynic migraineurs pain free after the window for triptan therapy has expired? Methods. Patients exhibiting migraine with allodynia were divided in two groups (n=14, each): group 1 received delayed sumatriptan injection (6 mg) 4 hours after onset of attack-which failed to render them pain free-and ketorolac infusion (two 15 mg boluses) 2 hours later; group 2 received delayed ketorolac monotherapy 4 hours after onset of attack. Pain intensity (visual analog scale) and skin sensitivity (quantitative sensory testing) were measured when the patients were migraine free (baseline); 4 hours after onset of migraine (just before treatment); 2 hours after sumatriptan; 1 hour after ketorolac. In the rat, we tested whether infusion of ketorolac (0.4 mg/kg) or indomethacin (1 mg/kg) will block ongoing sensitization in peripheral and central trigeminovascular neurons. The induction of sensitization (using topical application of inflammatory soup on the dura)and its suppression by COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity and responses to mechanical and thermal stimuli. Results. Patients had normal skin sensitivity in the absence of migraine, and presented cutaneous allodynia 4 hours after onset of migraine. In group 1, all patients continued to exhibit allodynia 2 hours after sumatriptan treatment, and none of them became pain free. However, 71%and 64%of the patients in groups 1 and 2, respectively, were rendered free of pain and allodynia within 60 minutes of ketorolac infusion. Nonresponders from both groups, in contrast to the responders, had had a history of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked sensitization in meningeal nociceptors and suppressed ongoing sensitization in spinal trigeminovascular neurons. This inhibitory action was reflected by normalization of neuronal firing rate and attenuation of neuronal responsiveness to mechanical stimulation of the dura, as well as mechanical and thermal stimulation of the skin. Conclusions. The termination of migraine with ongoing allodynia using COX1/COX2 inhibitors is achieved through the suppression of central sensitization. Although parenteral administration of COX1/COX2 inhibitors is impractical as routine migraine therapy, it should be the rescue therapy of choice for patients seeking emergency care for migraine. These patients should never be treated with opioids, particularly if they had no prior opioid exposure.
文摘Background and aims: Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain, suggesting the presence of hyperalgesia. It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations. In the former case, hyperalgesia should occur when intensity of non-painful sensations is still low. The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways. Methods: Forty eight consecutive dyspeptic patients (35 female) underwent gastric sensitivity testing with a barostat balloon using a double random staircase protocol. At the end of every distending step, patients scored perception of upper abdominal sensations on a graphic 0-6 rating scale and completed visual analogue scales (VAS 0-100 mm) for pain, nausea, satiety, and fullness. The end point was a rating scale of 5 or more. Results: Hypersensitivity was present in 20 patients (40%); gastric compliance did not differ between normo-and hypersensitive patients. At maximal distension (score 5 or more), hypersensitive patients had significantly lower distending pressures and intra-balloon volumes, but similar VAS scores for pain, nausea, satiety, and fullness compared with normosensitive patients. In both normosensitive and hypersensitive patients, elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea, satiety, and fullness. Conclusions: Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures. Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations. These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity.
文摘An increasing incidence of allergic bronchopulmonary aspergillosis (ABPA) as a complication in patients with cystic fibrosis (CF) is reported. The objective of this retrospective case-control study was to assess potential risk factors for ABPA and for Aspergillus fumigatus sensitisation (AFS). In a group of 160 CF patients, 11 (7% ) fulfilled the diagnostic criteria for ABPA and 20 (13% ) had evidence of AFS. They were compared to 62 control CF patients (25 for ABPA and 37 for AFS group) without evidence of ABPA or AFS using extended matching for sex, age and weight. AFS patients had received significantly higher cumulative doses of inhaled corticosteroids than their respective controls (OR 8.0; 95% CI 1.74-63). Bronchial colonisation with Stenotropho monasmaltophilia was strongly and independently associated with ABPA (OR 20; 95% CI 2.8-infinity). A longer duration of Pseudomonas aeruginosa colonisation was independently associated with AFS (OR per year 1.50; 95% CI 1.12-infinity). Conclusion: Cystic fibrosis patients with allergic bronchopulmonary aspergillosis have a more frequent isolation of S. maltophilia in their sputum than their controls. Longer duration of colonisation with P. aeruginosa is a risk factor for Aspergillus fumigatus sensitisation. Higher cumulative doses of inhaled corticosteroids are associated with Aspergillus fumigatus sensitisation and their role as a risk factor needs to be clarified.
