Brain : a journal of neurology
-
Randomized Controlled Trial Clinical Trial
Peripheral opioid analgesia in experimental human pain models.
This placebo-controlled, double-blind crossover study assessed whether exclusive activation of peripheral opioid receptors results in significant pain reduction. To achieve opioid activity restricted to the periphery, we used a short-term (2 h) low dose infusion of morphine-6-beta-glucuronide (M6G) because M6G does not pass the blood-brain barrier during this time in amounts sufficient to induce CNS effects. The lack of central opioid effects of M6G was confirmed by a lack of change of the pupil size and absence of other opioid-related CNS effects. ⋯ Subcutaneous tissue concentrations of M6G and morphine as assessed with microdialysis were about half those of the respective plasma concentrations. The results of the study indicate that M6G has antihyperalgesic effects in inflammatory pain through activation of peripheral opioid receptors. Since this occurs at concentrations that do not cause central opioid effects, M6G might be useful as a peripheral opioid analgesic.
-
Comparative Study
Pneumococcal meningitis in adults: spectrum of complications and prognostic factors in a series of 87 cases.
Studies on the incidence and spectrum of complications and prognostic factors in adults with pneumococcal meningitis are scarce. Therefore, we analysed 87 consecutive cases who were treated in our department between 1984 and 2002. Meningitis-associated intracranial complications developed in 74.7% and systemic complications in 37.9% of cases. ⋯ The morbidity and mortality of pneumococcal meningitis in adults are still devastating. We report higher incidences (diffuse brain swelling, hydrocephalus, cerebrovascular complications) or new incidences (myelitis, hearing loss, subarachnoid bleeding) of intracranial complications. Our detailed analysis of prognostic factors may help clinicians to identify patients at risk and may also be helpful in the design of clinical trials.
-
Comparative Study Clinical Trial Controlled Clinical Trial
Effect of chronic bilateral subthalamic nucleus (STN) stimulation on postural control in Parkinson's disease.
Postural instability is one of the most incapacitating factors in Parkinson's disease (PD). The underlying deficits and the effects of treatment are still not well understood. The aims of the present study were: (i) to identify abnormalities of postural control in PD patients during unperturbed stance and externally perturbed stance (anterior-posterior tilts of the support surface and of the visual scene); (ii) to assess the effects of L-dopa medication and subthalamic nucleus (STN) stimulation on posture control; and (iii) to characterize potential differential or additive effects of both treatments. ⋯ This finding suggests that PD patients lack the ability of normal subjects to use sensory or cognitive information when suppressing the destabilizing effect of visual tilt. These abnormal tilt reactions of the patients were resistant to treatment with L-dopa, STN stimulation and a combination of the two. Overall, the effects of STN stimulation on posture control essentially paralleled those of L-dopa during both unperturbed and externally perturbed stance.
-
Comparative Study Clinical Trial
Comparison of the pain suppressive effects of clinical and experimental painful conditioning stimuli.
Studies in healthy volunteers suggested that the classical counterirritation phenomenon (i.e. pain inhibits pain effect) might depend on diffuse noxious inhibitory controls (DNIC), which modulate the spinal transmission of nociceptive signals. In the present study, we sought to determine whether similar mechanisms were at play in patients with different subtypes of neuropathic pain. Ten patients presenting with a traumatic peripheral nerve injury associated with dynamic mechano-allodynia (i.e. pain triggered by brushing) or static mechano-allodynia (i.e. pain triggered by light pressure stimuli) were included in this study. ⋯ These effects were similar to those induced by HNCS and were probably due to an increased activation of DNIC. In contrast, in patients with dynamic allodynia, brushing within the allodynic area reduced the pain sensation at the foot, but did not inhibit the electrophysiological responses, suggesting that in this case the counterirritation effect may take place at the supraspinal level. Thus, the mechanisms of counterirritation are not univocal, but depend on the pathophysiological mechanisms of clinical pain.
-
Clinical Trial
Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation.
Frontal lobe activity during pain is generally linked to attentional processing. We addressed the question of whether 'bottom-up' processing and 'top-down' modulation of nociceptive information dissociate anatomically within the frontal lobe by using PET scanning during painful thermal stimulation of normal and capsaicin-treated skin. We showed recently that pain following normally non-painful heat stimuli on chemically irritated skin (heat allodynia) uniquely engages extensive areas of the bilateral dorsolateral prefrontal (DLPFC), ventral/orbitofrontal (VOFC) and perigenual anterior cingulate (ACC) cortices. ⋯ The inter-regional correlation of midbrain and medial thalamic activity was significantly reduced during high left DLPFC activity, suggesting that its negative correlation with pain affect may result from dampening of the effective connectivity of the midbrain-medial thalamic pathway. In contrast, right DLPFC activity was associated with a weakened relationship of the anterior insula with both pain intensity and affect. We propose that the DLPFC exerts active control on pain perception by modulating corticosubcortical and corticocortical pathways.