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Carlo A Porro

Publications and source records attributed to Carlo A Porro.

8 recordsLinked to original sources

Corticospinal excitability during painful self-stimulation in humans: a transcranial magnetic stimulation study.

We investigated changes in the corticospinal pattern of activity in healthy volunteers during sustained noxious and non-noxious mechanical stimulation of the first hand digit, resulting from active (self-stimulation) or passive (externally-induced) pressing against a sharp or blunted tip. The results indicate that, in order to press a finger onto a noxious stimulus with the same force generated to press onto a non-noxious one, the motor cortex adopts a peculiar strategy in terms of recruitment of motor units. This is reflected by an increase of corticospinal excitability (as revealed by motor potentials evoked by transcranial magnetic stimulation of the contralateral primary motor cortex) and EMG activity of agonist muscles, possibly related to an increase of motor unit synchronization.

Adult↗

Diurnal changes of tonic nociceptive responses in mice: evidence for a proalgesic role of melatonin.

Diurnal variations in tonic pain reactions have been described in mice tested in Spring, but the underlying mechanisms are still unknown. We tested the potential role of melatonin, a key hormone in the control of neuro-endocrine circadian rhythms. The experiments were performed in male CBA/J mice housed under controlled temperature, humidity, and light (12/12 dark/light cycle) conditions, during the Light (7-10a.m.) or Dark (7-10p.m.) phases of the diurnal cycle. In a first group of experiments, animals were either pretreated with i.p. saline (controls) or with the melatonin receptor antagonist, luzindole (30 mg/kg), before the s.c. injection of a dilute formalin solution into a hindpaw. In control animals, pain-related behavioral reactions (licking and flinching) were higher in the evening (Dark) than in the morning (Light), both during the first (0-10 min) and the second (11-55 min) phase of the response to s.c. formalin. In animals pre-treated with luzindole, no diurnal changes occurred, pain reactions in the Dark being similar to those of the Light Control group. In a second group of experiments, artificial pinealectomy, obtained by exposing animals to continuous light for 48 h, also reduced pain reactions in the evening to levels comparable to those in the morning. Receptor autoradiography showed lower binding availability at spinal cord level in mice sacrificed during the Dark, as expected from the circadian pattern of melatonin secretion. A further significant decrease of melatonin receptor binding was induced by noxious stimulation. These results suggest a proalgesic role of endogenous melatonin in tonic pain.

Animals↗

Independent time courses of supraspinal nociceptive activity and spinally mediated behavior during tonic pain.

The behavioral response to acute tissue injury is usually characterized by different phases, but the brain mechanisms underlying changes in pain-related behavior over time are still poorly understood. We aimed to analyze time-dependent changes in metabolic activity levels of 49 forebrain structures in the formalin pain model, using the autoradiographic 2-deoxyglucose method in unanesthetized, freely moving rats. We examined rats during the first phase of pain-related reactions ('early' groups), or during the third recovery phase, 60 min later, when the supraspinally mediated behavioral responses were reduced ('late' group). In the early groups, metabolic rates were bilaterally increased over control values in the periaqueductal gray, zona incerta and in several thalamic nuclei (anteroventral, centrolateral, lateral dorsal, parafascicular, posteromedial, submedius, ventromedial, and ventrobasal complex), as well as in the habenulae and in the parietal, cingulate, antero-dorsal insular, and anterior piriform cortex. A contralateral, somatotopically specific activation was found in the putative hindlimb representation area of the somatosensory cortex. In the late group, noxious-induced activation declined in most structures. However, metabolic rates were higher than controls in the periaqueductal gray and zona incerta and in two other structures not previously active: the prerubral area/field of Forel and the arcuate hypothalamic nucleus. These findings provide a time-dependent functional map of nociceptive and anti-nociceptive forebrain circuits during tonic pain. The parallel decrease in licking behavior and forebrain activity, at times when spinally mediated limb flexion responses were still present, suggests that endogenous antinociceptive systems may differently modulate spinal and supraspinal nociceptive networks following acute tissue injury.

Animals↗

Functional activity mapping of the mesial hemispheric wall during anticipation of pain.

The relative contributions of autonomic arousal and of cognitive processing to cortical activity during anticipation of pain, and the role of changes in thalamic outflow, are still largely unknown. To address these issues, we investigated with functional magnetic resonance imaging (fMRI) the activity of the contralateral mesial hemispheric wall in 56 healthy volunteers while they expected the stimulation of one foot, which could be either painful or innocuous. The waiting period was characterized by emotional arousal, a moderate rise in heart rate, and by increases in mean fMRI signals in the medial thalamus, mid- and posterior cingulate cortex, and in the putative foot area of the primary somatosensory and motor cortex. The same brain regions, excepting posterior cingulate, were also activated by somatosensory stimulation. We identified by cross-correlation analysis a cluster population whose fMRI signal time course was related to the mean heart rate (HR) profile, showing selective changes of activity during the waiting period. Positively correlated clusters were found mainly in sensorimotor areas, mid- and posterior cingulate, and dorsomedial prefrontal cortex. Negatively correlated clusters predominated in the perigenual anterior cingulate and ventromedial prefrontal cortex. HR clusters had different characteristics from, and showed limited spatial overlap with, clusters whose fMRI signals were related to the psychophysical pain intensity profile; however, both cluster populations were affected by anticipation. These findings unravel a complex pattern of brain activity during uncertain anticipation of noxious input, likely related both to changes in the level of arousal and to cognitive modulation of the pain system.

Adult↗

Functional imaging and pain: behavior, perception, and modulation.

Time-dependent increases of local metabolic or blood flow rates have been described in spinal cord and brain during acute and chronic pain states in experimental animals, in parallel with changes of different behavioral endpoints of pain and hyperalgesia. In healthy human volunteers, pain intensity-related hemodynamic changes have been identified in a widespread, bilateral brain system including parietal, insular, cingulate, and frontal cortical areas, as well as thalamus, amygdala, and midbrain. Specific patterns of activity may characterize hyperalgesic states and some chronic pain conditions. Forebrain nociceptive systems are under inhibitory control by endogenous opioids and can be affected by acute administration of mu-opioid receptor agonists. Anticipation of pain may in itself induce changes in brain nociceptive networks. Moreover, pain-related cortical activity can be modulated by hypnotic suggestions, focusing or diverting attention, and placebo. These findings begin to disclose the spatio-temporal dynamics of brain networks underlying pain perception and modulation.

Animals↗

Does anticipation of pain affect cortical nociceptive systems?

Anticipation of pain is a complex state that may influence the perception of subsequent noxious stimuli. We used functional magnetic resonance imaging (fMRI) to study changes of activity of cortical nociceptive networks in healthy volunteers while they expected the somatosensory stimulation of one foot, which might be painful (subcutaneous injection of ascorbic acid) or not. Subjects had no previous experience of the noxious stimulus. Mean fMRI signal intensity increased over baseline values during anticipation and during actual stimulation in the putative foot representation area of the contralateral primary somatosensory cortex (SI). Mean fMRI signals decreased during anticipation in other portions of the contralateral and ipsilateral SI, as well as in the anteroventral cingulate cortex. The activity of cortical clusters whose signal time courses showed positive or negative correlations with the individual psychophysical pain intensity curve was also significantly affected during the waiting period. Positively correlated clusters were found in the contralateral SI and bilaterally in the anterior cingulate, anterior insula, and medial prefrontal cortex. Negatively correlated clusters were found in the anteroventral cingulate bilaterally. In all of these areas, changes during anticipation were of the same sign as those observed during pain but less intense ( approximately 30-40% as large as peak changes during actual noxious stimulation). These results provide evidence for top-down mechanisms, triggered by anticipation, modulating cortical systems involved in sensory and affective components of pain even in the absence of actual noxious input and suggest that the activity of cortical nociceptive networks may be directly influenced by cognitive factors.

Adult↗

Immobilization and restraint effects on pain reactions in animals.

Acute physical restraint represents a potent stressor in several animal species and is accompanied by a complex pattern of hormonal responses and functional changes in the central nervous system. Repeated immobilization leads to partial blunting of the behavioral and hormonal responses, with transient modifications of neurotransmitter systems in the brain. Pain reactions, as investigated by different kinds of nociceptive tests, are usually attenuated both during and immediately following acute immobilization and the analgesic effect of opiate compounds potentiated; these behavioral alterations may be attributed at least in part to activation of an endogenous opioid system. In some species, restraint may induce a reflex immobility (animal hypnosis or tonic immobility) which is also characterized by suppression of pain reactions in rabbits, probably subserved by different mechanisms. Analysis of available data suggests that pain testing in unanesthetized, restrained animals may involve alterations of the animal's reactivity to noxious stimuli.

Acetylcholine↗

Neural circuits involved in the recognition of actions performed by nonconspecifics: an FMRI study.

Functional magnetic resonance imaging was used to assess the cortical areas active during the observation of mouth actions performed by humans and by individuals belonging to other species (monkey and dog). Two types of actions were presented: biting and oral communicative actions (speech reading, lip-smacking, barking). As a control, static images of the same actions were shown. Observation of biting, regardless of the species of the individual performing the action, determined two activation foci (one rostral and one caudal) in the inferior parietal lobule and an activation of the pars opercularis of the inferior frontal gyrus and the adjacent ventral premotor cortex. The left rostral parietal focus (possibly BA 40) and the left premotor focus were very similar in all three conditions, while the right side foci were stronger during the observation of actions made by conspecifics. The observation of speech reading activated the left pars opercularis of the inferior frontal gyrus, the observation of lip-smacking activated a small focus in the pars opercularis bilaterally, and the observation of barking did not produce any activation in the frontal lobe. Observation of all types of mouth actions induced activation of extrastriate occipital areas. These results suggest that actions made by other individuals may be recognized through different mechanisms. Actions belonging to the motor repertoire of the observer (e.g., biting and speech reading) are mapped on the observer's motor system. Actions that do not belong to this repertoire (e.g., barking) are essentially recognized based on their visual properties. We propose that when the motor representation of the observed action is activated, the observer gains knowledge of the observed action in a "personal" perspective, while this perspective is lacking when there is no motor activation.

Adult↗