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Biomedical subjects

Jean-Claude Willer

Publications and source records attributed to Jean-Claude Willer.

12 recordsLinked to original sources
PubMed2006

Dyspnea as a noxious sensation: inspiratory threshold loading may trigger diffuse noxious inhibitory controls in humans.

Dyspnea, a leading respiratory symptom, shares many clinical, physiological, and psychological features with pain. Both activate similar brain areas. The neural mechanisms of dyspnea are less well described than those of pain. The present research tested the hypothesis of common pathways between the two sensations. Six healthy men (age 30-40 yr) were studied. The spinal nociceptive flexion reflex (RIII) was first established in response to electrical sural stimulation. Dyspnea was then induced through inspiratory threshold loading, forcing the subjects to develop 70% of their maximal inspiratory pressure to inhale. This led to progressive inhibition of the RIII reflex that reached 50 +/- 12% during the fifth minute of loading (P < 0.001), was correlated to the intensity of the self-evaluated respiratory discomfort, and had recovered 5 min after removal of the load. The myotatic H-reflex was not inhibited by inspiratory loading, arguing against postsynaptic alpha motoneuron inhibition. Dyspnea, like pain, thus induced counterirritation, possibly indicating a C-fiber stimulation and activation of diffuse noxious inhibitory descending controls known to project onto spinal dorsal horn wide dynamic range neurons. This confirms the noxious nature of certain types of breathlessness, thus opening new physiological and perhaps therapeutic perspectives.

Adult↗
PubMed2006

Is pain the price of empathy? The perception of others' pain in patients with congenital insensitivity to pain.

Empathy is a complex form of psychological inference that enables us to understand the personal experience of another person through cognitive/evaluative and affective processes. Recent findings suggest that empathy for pain may involve a 'mirror-matching' simulation of the affective and sensory features of others' pain. Despite such evidence for a shared representation of self and other pain at the neural level, the possible influence of the observer's own sensitivity to pain upon his perception of others' pain has not been investigated yet. The aim of this study was to explore how patients with congenital insensitivity to pain (CIP), who are largely deprived of common stimulus-induced pain experiences, perceive the pain of others. Ratings of verbally presented imaginary painful situations showed that CIP patients' semantic knowledge regarding the pain of others did not differ from control subjects. Moreover, the propensity to infer pain from facial expressions was very similar between CIP patients and control subjects. On the other hand, when asked to rate pain-inducing events seen in video clips in the absence of visible or audible pain-related behaviour, CIP patients showed more variable and significantly lower pain ratings, as well as a reduction in aversive emotional responses, compared with control subjects. Interestingly, pain judgements, inferred either from facial pain expressions or from pain-inducing events, were strongly related to inter-individual differences in emotional empathy among CIP patients, while such correlation between pain judgement and empathy was not found in control subjects. The results suggest that a normal personal experience of pain is not necessarily required for perceiving and feeling empathy for others' pain. In the absence of functional somatic resonance mechanisms shaped by previous pain experiences, others' pain might be greatly underestimated, however, especially when emotional cues are lacking, unless the observer is endowed with sufficient empathic abilities to fully acknowledge the suffering experience of others in spite of his own insensitivity.

Adolescent↗
PubMed2006

Psychophysical study of the effects of topical application of menthol in healthy volunteers.

Cold hyperalgesia is a major clinical phenomenon, but validated experimental models are still lacking for humans. Topical menthol application has recently been proposed as a possible model for the study of cold pain. We characterized the psychophysical effects of 30% l-menthol in ethanol on glabrous skin in 39 healthy subjects, using a double-blind, randomized, crossover design, with ethanol as a control. Psychophysical testing included an assessment of pain thresholds and detection of mechanical, cold, and heat stimuli, and of the sensations induced by suprathreshold stimuli. Most subjects (90%) perceived a cooling sensation with menthol. Menthol decreased cold pain thresholds and enhanced pain responses to suprathreshold noxious cold stimuli, without affecting responses to other stimuli. Menthol therefore has selective effects on noxious cold processing. No subject displayed signs of skin irritation or redness. These data suggest that 30% menthol application may be a useful experimental model for studies of cold hyperalgesia in humans. The absence of local skin reactions also makes this test potentially suitable for use in patients.

Administration, Topical↗
PubMed2006

Cold extends electromyography distinction between ion channel mutations causing myotonia.

OBJECTIVE: Myotonias are inherited disorders of the skeletal muscle excitability. Nondystrophic forms are caused by mutations in genes coding for the muscle chloride or sodium channel. Myotonia is either relieved or worsened by repeated exercise and can merge into flaccid weakness during exposure to cold, according to causal mutations. We designed an easy electromyography (EMG) protocol combining repeated short exercise and cold as provocative tests to discriminate groups of mutations. METHODS: Surface-recorded compound muscle action potential was used to monitor muscle electrical activity. The protocol was applied on 31 unaffected control subjects and on a large population of 54 patients with chloride or sodium channel mutations known to cause the different forms of myotonia. RESULTS: In patients, repeated short exercise test at room temperature disclosed three distinct abnormal patterns of compound muscle action potential changes (I-III), which matched the clinical symptoms. Combining repeated exercise with cold exposure clarified the EMG patterns in a way that enabled a clear correlation between the electrophysiological and genetic defects. INTERPRETATION: We hypothesize that segregation of mutations into the different EMG patterns depended on the underlying pathophysiological mechanisms. Results allow us to suggest EMG guidelines for the molecular diagnosis, which can be used in clinical practice.

Action Potentials↗
PubMed2005

Effortless control: executive attention and conscious feeling of mental effort are dissociable.

Recruitment of executive attention is normally associated to a subjective feeling of mental effort. Here we investigate the nature of this coupling in a patient with a left mesio-frontal cortex lesion including the anterior cingulate cortex (ACC), and in a group of comparison subjects using a Stroop paradigm. We show that in normal subjects, subjective increases in effort associated with executive control correlate with higher skin-conductance responses (SCRs). However, our patient experienced no conscious feeling of mental effort and showed no SCR, in spite of exhibiting normal executive control, and residual right anterior cingulate activity measured with event-related potentials (ERPs). Finally, this patient demonstrated a pattern of impaired behavior and SCRs in the Iowa gambling task-elaborated by Damasio, Bechara and colleagues-replicating the findings reported by these authors for other patients with mesio-frontal lesions. Taken together, these results call for a theoretical refinement by revealing a decoupling between conscious cognitive control and consciously reportable feelings. Moreover, they reveal a fundamental distinction, observed here within the same patient, between the cognitive operations which are depending on normal somatic marker processing, and those which are withstanding to impairments of this system.

Adult↗
PubMed2005

Hyperalgesia and allodynia: peripheral mechanisms.

Nociceptive signals are generated by peripheral sensory organs called nociceptors, which are endings of small-diameter nerve fibers responsive to the tissue environment. The myriad chemical mediators capable of activating, sensitizing, or arousing nociceptors include kinins, proinflammatory and anti-inflammatory cytokines, prostanoids, lipooxygenases, the "central immune response mediator" NF-kappaB, neurotrophins and other growth factors, neuropeptides, nitric oxide, histamine, serotonin, proteases, excitatory amino acids, adrenergic amines, and opioids. These mediators may act in combination or at a given time in the inflammatory process, producing subtle changes that result in hyperalgesia or allodynia. We will review the most extensively studied molecular and cellular mechanisms underlying these two clinical abnormalities. The role of the peripheral nervous system in progression of inflammatory joint disease to chronicity is discussed.

Humans↗
PubMed2004

Electromyography guides toward subgroups of mutations in muscle channelopathies.

Myotonic syndromes and periodic paralyses are rare disorders of skeletal muscle characterized mainly by muscle stiffness or episodic attacks of weakness. Familial forms are caused by mutations in genes coding for skeletal muscle voltage-gated ion channels. Exercise is known to trigger, aggravate, or relieve the symptoms. Therefore, exercise can be used as a functional test in electromyography to improve the diagnosis of these muscle disorders. Abnormal changes in the compound muscle action potential can be disclosed using different exercise tests. We report the outcome of an inclusive electromyographic survey of a large population of patients with identified ion channel gene defects. Standardized protocols comprising short and long exercise tests were applied on 41 unaffected control subjects and on 51 case patients with chloride, sodium, or calcium channel mutations known to cause myotonia or periodic paralysis. These tests disclosed significant changes of compound muscle action potential, which generally matched the clinical symptoms. Combining the responses to the different tests defined five electromyographic patterns (I-V) that correlated with subgroups of mutations and may be used in clinical practice as guides for molecular diagnosis. We hypothesize that mutations are segregated into the different electromyographic patterns according to the underlying pathophysiological mechanisms.

Action Potentials↗
PubMed2004

Preserved auditory cognitive ERPs in severe akinetic mutism: a case report.

kinetic mustism is a dramatic deficit in spontaneous initiation of voluntary motor and speech acts, usually secondary to bilateral lesions of the anterior cingulate cortices and supplementary motor areas [Principles of Neurology, McGraw-Hill, New York, 1989]. Given the obvious limitations of traditional neuropsychological testing in this clinical context, the use of neurophysiological tools such as bedside auditory cognitive event-related potentials (ERPs), recently proven to be relevant to evaluate comatose and vegetative patients [Clin. Neurophysiol. 110 (9) (1999) 1601; News Physiol. Sci. 17 (2002) 38], may constitute an interesting alternative. Here, we present the ERPs of a 38-year-old right-handed woman with severe akinetic mutism recorded in a passive auditory odd-ball paradigm. In spite of this severe clinical state, we could observe the presence of a "Mismatch Negativity", and of a larger P300 in rare trials than in frequent ones. By revealing a high level of cognitive integration of environmental auditory information, our study emphasizes the potential clinical relevance of MMN and P300 recordings in akinetic mutism to assess patient cognitive functioning.

Adult↗
PubMed2002

Depressant effect on a C-fibre reflex in the rat, of RB101, a dual inhibitor of enkephalin-degrading enzymes.

The effect of N-[(R,S)-2-benzyl-3[(S)-(2-amino-4-methylthio)butyldithiol]-1-oxopropyl]-L-phenylalanine benzyl ester (RB101), a dual inhibitor of the enkephalin-degrading enzymes, neutral endopeptidase and aminopeptidase N, was assessed in anaesthetised rats on the C-fibre reflex elicited by electrical stimulation within the sural nerve territory and recorded from the ipsilateral biceps femoris muscle. The temporal evolution of the pharmacological response was monitored by the repeated application of a constant stimulus intensity, namely three times threshold (3 T). In addition, recruitment curves were built by varying the stimulus intensity from 0 to 7 T. RB101 (7.5, 15 and 30 mg kg(-1), i.v.) induced a dose-dependent, naloxone-reversible depression of the reflex, which lasted around 60 min with the highest dose. The ED(50) was calculated as 16.9 mg kg(-1). Analyses of the recruitment curves revealed: (1) a significant increase of threshold; (2) a significant depression of the reflex in the ascending part of the curve; and (3) a lack of major depressive effects on the responses elicited by the strongest stimuli (corresponding to the plateau of the curve). The increase in the nociceptive threshold by enkephalin-degrading enzyme inhibitors, confirms previous data obtained from behavioural tests. In addition, the present study revealed an efficacy of these compounds over a wide range of stimulus intensities, albeit excluding the highest.

Aminopeptidases↗
PubMed1982

Comparative effects of electroacupuncture and transcutaneous nerve stimulation on the human blink reflex.

The effects of low frequency (2 Hz) high intensity (10-12 mA) (electroacupuncture, EA) and of high frequency (100 Hz) low intensity (2 mA) (transcutaneous nerve stimulation, TNS) conditioning stimuli were studied on the nociceptive component (R2) of the blink reflex in normal volunteers. EA induced a progressive and moderate partially naloxone-reversible depression in the R2 response. In contrast, TNS induced a rapid and major depression in this reflex. In this latter case, naloxone failed to produce any reversal effect. These two patterns of data are discussed and further electrophysiological studies provide some evidence for two different mechanisms in the depressive effects of EA and TNS upon the nociceptive component of the blink reflex in man.

Acupuncture Therapy↗