Silvestro Roatta

Influence of sympathetic nervous system on sensorimotor function: whiplash associated disorders (WAD) as a model.

There is increasing interest about the possible involvement of the sympathetic nervous system (SNS) in initiation and maintenance of chronic muscle pain syndromes of different aetiology. Epidemiological data show that stresses of different nature, e.g. work-related, psychosocial, etc., typically characterised by SNS activation, may be a co-factor in the development of the pain syndrome and/or negatively affect its time course. In spite of their clear traumatic origin, whiplash associated disorders (WAD) appear to share many common features with other chronic pain syndromes affecting the musculo-skeletal system. These features do not only include symptoms, like type of pain or sensory and motor dysfunctions, but possibly also some of the pathophysiological mechanisms that may concur to establish the chronic pain syndrome. This review focuses on WAD, particular emphasis being devoted to sensorimotor symptoms, and on the actions exerted by the sympathetic system at muscle level. Besides its well-known action on muscle blood flow, the SNS is able to affect the contractility of muscle fibres, to modulate the proprioceptive information arising from the muscle spindle receptors and, under certain conditions, to modulate nociceptive information. Furthermore, the activity of the SNS itself is in turn affected by muscle conditions, such as its current state of activity, fatigue and pain signals originating in the muscle. The possible involvement of the SNS in the development of WAD is discussed in light of the several positive feedback loops in which it is implicated.

Sympathetic modulation of muscle spindle afferent sensitivity to stretch in rabbit jaw closing muscles

Previous reports showed that sympathetic stimulation affects the activity of muscle spindle afferents (MSAs). The aim of the present work is to study the characteristics of sympathetic modulation of MSA response to stretch: (i) on the dynamic and static components of the stretch response, and (ii) on group Ia and II MSAs to evaluate potentially different effects. In anaesthetised rabbits, the peripheral stump of the cervical sympathetic nerve (CSN) was stimulated at 10 impulses s−1 for 45–90 s. The responses of single MSAs to trapezoidal displacement of the mandible were recorded from the mesencephalic trigeminal nucleus. The following characteristic parameters were determined from averaged trapezoidal responses: initial frequency (IF), peak frequency at the end of the ramp (PF), and static index (SI). From these, other parameters were derived: dynamic index (DI = PF ‐ SI), dynamic difference (DD = PF ‐ IF) and static difference (SD = SI ‐ IF). The effects of CSN stimulation were also evaluated during changes in the state of intrafusal muscle fibre contraction induced by succinylcholine and curare. In a population of 124 MSAs, 106 units (85.4 %) were affected by sympathetic stimulation. In general, while changes in resting discharge varied among different units (Ia vs. II) and experimental conditions (curarised vs. non‐curarised), ranging from enhancement to strong depression of firing, the amplitude of the response to muscle stretches consistently decreased. This was confirmed and detailed in a quantitative analysis performed on 49 muscle spindle afferents. In both the non‐curarised (23 units) and curarised (26 units) condition, stimulation of the CSN reduced the response amplitude in terms of DD and SD, but hardly affected DI. The effects were equally present in both Ia and II units; they were shown to be independent from gamma drive and intrafusal muscle tone and not secondary to muscle hypoxia. Sympathetic action on the resting discharge (IF) was less consistent. In the non‐curarised condition, IF decreased in most Ia units, while in II units decreases and increases occurred equally often. In the curarised condition, IF in group II units mostly increased. The results have important functional implications on the control of motor function in a state of ‘high’ sympathetic activity, like excessive stress, as well as in certain pathological conditions such as sympathetically maintained pain.

Sympathetic‐induced changes in discharge rate and spike‐triggered average twitch torque of low‐threshold motor units in humans

Animal and in vitro studies have shown that the sympathetic nervous system modulates the contractility of skeletal muscle fibres, which may require adjustments in the motor drive to the muscle in voluntary contractions. In this study, these mechanisms were investigated in the tibialis anterior muscle of humans during sympathetic activation induced by the cold pressor test (CPT; left hand immersed in water at 4°C). In the first experiment, 11 healthy men performed 20 s isometric contractions at 10% of the maximal torque, before, during and after the CPT. In the second experiment, 12 healthy men activated a target motor unit at the minimum stable discharge rate for 5 min in the same conditions as in experiment 1. Intramuscular electromyographic (EMG) signals and torque were recorded and used to assess the motor unit discharge characteristics (experiment 1) and spike‐triggered average twitch torque (experiment 2). CPT increased the diastolic blood pressure and heart rate by (mean ±s.d.) 18 ± 9 mmHg and 4.7 ± 6.5 beats min−1 (P < 0.01), respectively. In experiment 1, motor unit discharge rate increased from 10.4 ± 1.0 pulses s−1 before to 11.1 ± 1.4 pulses s−1 (P < 0.05) during the CPT. In experiment 2, the twitch half‐relaxation time decreased by 15.8 ± 9.3% (P < 0.05) during the CPT with respect to baseline. These results provide the first evidence of an adrenergic modulation of contractility of muscle fibres in individual motor units in humans, under physiological sympathetic activation.

Effect of generalised sympathetic activation by cold pressor test on cerebral haemodynamics in healthy humans.

There is no general agreement regarding several aspects of the role of the sympathetic system on cerebral haemodynamics such as extent of effectiveness, operational range and site of action. This study was planned to identify the effect of a generalised sympathetic activation on the cerebral haemodynamics in healthy humans before it is masked by secondary corrections, metabolic or myogenic in nature. A total of 35 healthy volunteers aged 20-35 underwent a 5 min lasting cold pressor test (CPT) performed on their left hand. The cerebral blood flow (CBF) velocity in the middle cerebral arteries and arterial blood pressure were recorded with transcranial Doppler sonography and with a non-invasive finger-cuff method, respectively. The ratio of arterial blood pressure to mean blood velocity (ABP/Vm) and Pulsatility Index (PI) were calculated throughout each trial. CPT induced an increase in mean ABP (range 2-54 mmHg depending on the subject) and only a slight, though significant, increase in blood velocity in the middle cerebral artery (+2.4 and +4.4% on ipsi- and contralateral side, respectively). During CPT, the ratio ABP/Vm increased and PI decreased in all subjects on both sides. These changes began simultaneously with the increase in blood pressure. The increase in ABP/Vm ratio is attributed to an increase in the cerebrovascular resistance, while the concomitant reduction in PI is interpreted as due to the reduction in the compliance of the middle cerebral artery. The results suggest that generalised increases in the sympathetic discharge, causing increases in ABP, can prevent concomitant increases in CBF by acting on both small resistance and large compliant vessels. This effect is also present when a slight increase in blood pressure occurs, which suggests a moderate increase in the sympathetic discharge, i.e. when ABP remains far below the upper limit of CBF autoregulation.

Sympathetic actions on the skeletal muscle

The sympathetic nervous system (SNS) modulates several functions in skeletal muscle fibers, including metabolism, ionic transport across the membrane, and contractility. These actions, together with the sympathetic control of other organ systems, support intense motor activity. However, some SNS actions on skeletal muscles may not always be functionally advantageous. Implications for motor control and sport performance are discussed.

Influence of cutaneous and muscular circulation on spatially resolved versus standard Beer–Lambert near‐infrared spectroscopy

The potential interference of cutaneous circulation on muscle blood volume and oxygenation monitoring by near‐infrared spectroscopy (NIRS) remains an important limitation of this technique. Spatially resolved spectroscopy (SRS) was reported to minimize the contribution of superficial tissue layers in cerebral monitoring but this characteristic has never been documented in muscle tissue monitoring. This study aims to compare SRS with the standard Beer–Lambert (BL) technique in detecting blood volume changes selectively induced in muscle and skin. In 16 healthy subjects, the biceps brachii was investigated during isometric elbow flexion at 70% of the maximum voluntary contractions lasting 10 sec, performed before and after exposure of the upper arm to warm air flow. From probes applied over the muscle belly the following variables were recorded: total hemoglobin index (THI, SRS‐based), total hemoglobin concentration (tHb, BL‐based), tissue oxygenation index (TOI, SRS‐based), and skin blood flow (SBF), using laser Doppler flowmetry. Blood volume indices exhibited similar changes during muscle contraction but only tHb significantly increased during warming (+5.2 ± 0.7 μmol/L·cm, an effect comparable to the increase occurring in postcontraction hyperemia), accompanying a 10‐fold increase in SBF. Contraction‐induced changes in tHb and THI were not substantially affected by warming, although the tHb tracing was shifted upward by (5.2 ± 3.5 μmol/L·cm, P < 0.01). TOI was not affected by cutaneous warming. In conclusion, SRS appears to effectively reject interference by SBF in both muscle blood volume and oxygenation monitoring. Instead, BL‐based parameters should be interpreted with caution, whenever changes in cutaneous perfusion cannot be excluded.

The pain-induced decrease in low-threshold motor unit discharge rate is not associated with the amount of increase in spike-triggered average torque

OBJECTIVE Activation of nociceptive afferents decreases motor unit discharge rates in static contractions. There is also evidence that during experimental muscle pain the motor unit twitch force increases, which has been hypothesized to compensate for the decrease in discharge rate to maintain constant force. This study examined whether there is an association between the magnitude of change in motor unit discharge rate and the amount of increase in the spike-triggered average torque during experimental muscle pain. METHODS Sixteen subjects performed three constant-torque isometric ankle dorsi-flexions at 10% of the maximal force (MVC) alternated with two contractions at constant discharge rate of a target motor unit, before and following injection of 0.5 ml of hypertonic (painful) or isotonic (control) saline into the tibialis anterior muscle. RESULTS The discharge rate of the target unit at 10% MVC decreased following injection of hypertonic saline (P<0.05; mean+/-SD, before: 9.9+/-1.3 pulses per second, pps; after injection: 8.9+/-1.0 pps). The peak of the spike-triggered average torque increased with pain (P<0.05; before: 0.56+/-0.55 mNm; during pain: 0.95+/-1.02 mNm) but the increase was not correlated with the decrease in discharge rate (R=0.08). Propagation velocity and action potential peak-to-peak amplitude did not change with pain. CONCLUSIONS The pain-induced modifications in the estimated motor unit twitch torque (1) were not caused by changes in muscle fiber action potential, and (2) were not associated with the decrease in discharge rate. SIGNIFICANCE Maintenance of constant force during static painful contractions is not explained by a matching between changes in contractile and control motor unit properties.

A comparative study of changes operated by sympathetic nervous system activation on spindle afferent discharge and on tonic vibration reflex in rabbit jaw muscles

The effect of sympathetic activation on the spindle afferent response to vibratory stimuli eliciting the tonic vibration reflex in jaw closing muscles was studied in precollicularly decerebrate rabbits. Stimulation of the cervical sympathetic trunk, at frequencies within the physiologic range, consistently induced a decrease in spindle response to muscle vibration, which was often preceded by a transient enhancement. Spindle discharge was usually correlated with the EMG activity in the masseter muscle and the tension reflexly developed by jaw muscles. The changes in spindle response to vibration were superimposed on variations of the basal discharge which exhibited different patterns in the studied units, increases in the firing rate being more frequently observed. These effects were mimicked by close arterial injection of the selective alpha 1-adrenoceptor agonist phenylephrine. Data presented here suggest that sympathetically-induced modifications of the tonic vibration reflex are due to changes exerted on muscle spindle afferent information.

Sympathetic control of skeletal muscle function: possible co-operation between noradrenaline and neuropeptide Y in rabbit jaw muscles

Stimulation of the cervical sympathetic nerve at 10/s increases by 12.9 +/- 0.7% peak tension of maximal twitches in the directly stimulated jaw muscles and markedly depresses (41.6 +/- 1.3%) the tonic vibration reflex (TVR) elicited in the same muscles by vibration of the mandible. Both effects are not significantly influenced by administration of beta-adrenoceptor antagonists. When both alpha- and beta-adrenergic receptors are blocked, sympathetic stimulation induces a very small increase in twitch tension (3.8 +/- 0.7%), while no detectable change in the TVR is observed. Close arterial injection of alpha 1-adrenoceptor agonist phenylephrine mimics the effects induced by sympathetic stimulation on twitch tension and TVR, dose-dependently. The noradrenaline co-transmitter neuropeptide Y also produces a long-lasting, dose-dependent increase in the twitch tension which is unaffected by blockade of adrenergic receptors as well as of the neuromuscular junctions. Contribution of neuropeptide Y to the sympathetically-induced reduction of the stretch reflex is not clearly demonstrated. These data suggest that co-operation between noradrenaline and neuropeptide Y may be effective in determining sympathetic modulation of skeletal muscle function.

The chromogranin A- derived N-terminal peptide vasostatin-I: In vivo effects on cardiovascular variables in the rabbit

This study is the first to report on vascular effect of the chromogranin A derived Vasostatin-I (CgA(1-76)) in vivo. Cardiovascular parameters were recorded in 29 rabbits with sympathetically decentralized right carotid vascular bed. The recombinant human STA CgA(1-78) (VS-1) was infused at 480 μg/kg over 25 min. Group I was kept awake while groups II-V were anesthetized with Ketamine-xylazine. VS-1 was given alone in groups I-II while in presence of either phentolamine, phentolamine plus propranolol or hexamethonium in groups III-V. Serum VS-1 peaked at 2 μg/ml (200 nM) before onset of vascular effects and declined rapidly to ~200 ng/ml within 30 min. In all groups but III and IV VS-1 induced a brief vasoconstriction, being larger in intact than in sympathetically decentralized beds. The VS-1 induced vasoconstriction was not altered by hexamethonium but was abolished by phentolamine. In presence of the α-adrenergic blocker a long lasting vasodilatation, unaffected by propranolol, was apparent on both innervated and decentralized sides. In conclusion, VS-1 induced an α-adrenoceptor-mediated vasoconstriction presumably brought about by noradrenaline release from sympathetic nerves when infused at a dose giving an initial serum concentration of ~200 nM. This initial vasoconstriction masked a persistent adrenoceptor-independent vasodilatation, consistent with previous reports from in vitro models.