Capsaicin-sensitive sensory neurons convey to the central nervous system signals (chemical and physical) arising from viscera and the skin which activate a variety of visceromotor and neuroendocrine reflexes integrated at various levels (intramurally in peripheral organs, at level of prevertebral ganglia, spinal and supraspinal level). Much evidence is now available that peripheral terminals of certain sensory neurons, widely distributed in skin and viscera have the ability to release, upon adequate stimulation, their transmitter content. In addition to the well-known "axon reflex" arrangement, the capsaicin-sensitive sensory neurons have the ability to release the stored transmitter also from the same terminal which is excited by the environmental stimulus. The efferent function of these sensory neurons is realized through the direct and indirect (i.e. mediated by activation of other cells) effects of released mediators. The action of released transmitters on postjunctional elements covers a wide range of effects which may have a physiological or pathological relevance. Development of drugs capable of controlling the sensory-efferent functions of the capsaicin-sensitive sensory neurons represent a new and very promising area of research for pharmacological treatment of various human diseases.

The sensory-efferent function of capsaicin-sensitive sensory neurons

▪ Abstract Breathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBotzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.

Breathing: Rhythmicity, plasticity, chemosensitivity

Nociception from skeletal muscle in relation to clinical muscle pain.

Tachykinin receptors and tachykinin receptor antagonists

Microdialysis—Theory and application

The high incidence of serious chest infections in patients with Parkinson's disease is unexplained, but an impairment in cough reflex may have a role Maximal voluntary cough (MVC) and reflex cough (RC) to inhalation of ultrasonically nebulized distilled water were analyzed in patients with Parkinson's disease and age-matched control subjects by monitoring the integrated electromyographic activity (IEMG) of abdominal muscles The peak amplitude of IEMG activity (IEMGP) was expressed as a fraction of the highest IEMGP value observed during MVC corrected to account for possible losses in abdominal muscle force due to reduced central muscle activation Cough intensity was indexed in terms of both the IEMGP and the ratio of IEMGP to the duration of the expiratory ramp (TEC), ie, the rate of rise of IEMG activity Cough threshold was slightly higher in patients than in control subjects, but the difference failed to reach statistical significance Compared with control subjects, patients displayed a lower IEMGP during maximal expiratory pressure maneuvers (PEmax), MVC, and RC (p always < 001); TEC during RC was longer (p < 001) than in controls Consequently, the rate of rise of IEMG activity during cough was always lower in patients (p < 0 01), especially during RC Finally, PEmax, and both the peak and rate of rise of IEMG activity during RC were inversely related to the level of clinical disability (Spearman rank correlation coefficient, rs = -088, -086, and -085, respectively, p always < 001) The results indicate that the central neural mechanisms subserving the recruitment of motor units and/or the increase in their frequency of discharge during voluntary and, even more markedly, RC are impaired in patients with Parkinson's disease

Defective Motor Control of Coughing in Parkinson's Disease

In vivo release of substance P in the nucleus tractus solitarii increases during hypoxia.

Unilateral focal cold blocks (20 degrees C) in structures located ventrolaterally in rostral medulla consistently caused apnoea or deep depression of inspiratory motor output. The inhibitory effect could be correlated with the cooling temperature. Apnoeic response occurred either with complete absence of any inspiratory activity or combined with low level tonic inspiratory motor activity ('tonic apnoea'). The appearance of apnoea was CO2-independent, whereas the tonic component of the latter increased with increasing levels of PCO2. The results suggest that the structures in the deep, ventro-lateral aspect of rostral medulla, from which apnoea can be induced, correspond partly to the nucleus paragigantocellularis lateralis (nPGL) and the nucleus preolivaris. These structures appear to be relevant for the drive inputs necessary for respiratory rhythmogenesis. Unilateral focal cooling in the rostral medulla, including the 'Botzinger Complex', caused increments in respiratory rate both in vagotomized and non-vagotomized animals. The increase in respiratory rate in response to cooling in the region of the 'Botzinger Complex' was combined with either an enhancement or some depression of respiratory motor output. This area in the rostral part of the ventral respiratory group (VRG) seems not to be crucial for respiratory rhythmogenesis, but to play a role in determining both the intensity and timing of the respiratory activity. All effects of unilateral cold block were bilaterally symmetrical.

Effects of graded focal cold block in rostral areas of the medulla.

In patients with Parkinson's disease who had never previously been treated with any antiparkinsonism drug, we studied the effects of L-dopa on ballistic arm abduction movement in a step-tracking task. L-Dopa treatment increased the mean velocity of the initial movement towards the target without loss of accuracy and with improved motor performance under open-loop conditions. Performance also improved in motor tasks with expected perturbation. EMG patterns of arm abduction movements showed abnormal features in untreated patients and improved after L-dopa treatment.

Human ballistic arm abduction movements Effects of L‐dopa treatment in Parkinson's disease

Electrical stimulation pain thresholds and EMG activity were studied, using the vastus medialis muscle of healthy control subjects and of patients with osteoarthritis of the knee. Various categories of sensation elicited by progressive increases of the level of electrical stimulation (including one defined as pain threshold) were defined for control subjects. For patients. muscular pain thresholds differed significantly for the two sides of the body; they were usually lower in the more affected side. Involuntary activity of certain motor units and delayed relaxation following voluntary contraction were consistently observed in patients. The involuntary activity was affected by limb position and by mechanical stimulation of tender areas of the muscle or joint. Differences in pain threshold between the two sides were significantly reduced and the EMG pattern became normal following treatment with injections of local anaesthetic into tender periarticular areas and systemic administration of lysine acetylsalicylate. In standing patients, abnormal EMG activity (which was characteristically sensitive to body load and its variations) was found. Injection of a local anaesthetic into the joint cavity was able to induce a rapid subjective improvement and a consistent reduction of EMG activity.

Tito Pantaleo

Papers

Defective Motor Control of Coughing in Parkinson's Disease

In vivo release of substance P in the nucleus tractus solitarii increases during hypoxia.

Effects of graded focal cold block in rostral areas of the medulla.

Human ballistic arm abduction movements Effects of L‐dopa treatment in Parkinson's disease

Pain thresholds and electromyographic features of periarticular muscles in patients with osteoarthritis of the knee