[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to investigate the effects of spinal recurrent inhibition on human motoneurone discharge patterns. The tonic discharge activity of motor unit pairs was recorded in the extensor carpi radialis (ECR) and abductor digiti minimi (ADM) muscles during voluntary isometric contraction. While undergoing continuous intravenous saline (NaCl 0.9 %) perfusion, the subjects were given a short lasting injection of L-acetylcarnitine (L-Ac), which has been found to potentiate recurrent inhibition in humans. The variability, synchronization and coherence of the motor unit discharges were analysed during four successive test periods (lasting 2-3 min each). A significant decrease in the inter-spike interval (ISI) coefficient of variation was observed in the discharge patterns of the motor units tested in the ECR and not in the ADM, which were not accompanied by any consistent changes in the mean ISIs of the motor unit activity in either muscle. The L-Ac injection also led to a significant increase in the synchronization in half of the motor unit pairs tested in the ECR muscle (n = 29), whereas no consistent changes were observed with the ADM motor units (n = 25). However, coherence analysis failed to reveal any consistent differences in the incidence of significant values of coherence spectrum between the pre-injection and injection periods among the motor unit pairs tested with either saline or L-Ac injections, in either the ECR or ADM muscles. The contrasting effects on the variability and the synchronization of the motor unit discharges observed with ECR motoneurones known to undergo recurrent inhibition and with ADM motoneurones known to lack recurrent inhibition suggest that the drug may have specific effects which are mediated by an enhancement of the Renshaw cell activity. The decrease in the ISI variability is in line with the hypothesis that recurrent inhibition may contribute along with the post-spike after-hyperpolarization to limiting the influence of the synaptic noise on the firing times of steadily discharging motoneurones. The present data, which suggest that recurrent inhibition plays a synchronizing rather than a desynchronizing role, are in keeping with the fact that the Renshaw cells may provide an important source of common inhibitory inputs.
The Journal of Physiology 05/2003; 548(Pt 2):615-29. DOI:10.1113/jphysiol.2002.033126 · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To test the hypothesis that 'metabolites released during fatiguing muscle contractions excite group III-IV muscle nociceptive afferents, inhibiting homonymous motoneurones via Renshaw cells,' by recording changes in recurrent inhibition of soleus motoneurones when high-threshold, small-diameter afferents (group III-IV fibres) from the same muscle were tonically activated.
Experiments were performed in 7 healthy subjects at rest and during weak isometric voluntary contraction of the soleus muscle. Muscle nociceptive afferents were activated by local standardized injection of levo-ascorbic acid. Renshaw cells were orthodromically activated by a conditioning H reflex and the resulting recurrent inhibition of the soleus motoneurones was assessed by a subsequent test H reflex. An additional H reflex of the same size as the test reflex was used to assess motoneurone excitability.
At rest, muscle nociceptive stimulation produced transient facilitation of both test H and reference H reflexes. Under weak voluntary contraction, muscle nociceptive stimulation produced long-lasting extra-inhibition and extra-facilitation of the test reflex and reference reflex respectively, the time course of which closely resembled that of the subjective muscle pain curve.
Discharge of putative group III-IV muscle afferents facilitated homonymous recurrent inhibition. The filtering property of recurrent inhibition may contribute to limit motoneurone activity during muscle pain and/or adapt motoneurone firing rate to the modified contractile properties of motor units as muscle fatigue developed.
[Show abstract][Hide abstract] ABSTRACT: Tonic muscle nociceptive discharge evoked chemically from the foot extensor digitorum brevis muscle in man produces a depression of Ia excitation and Ib inhibition of the soleus (Sol) motoneurones (Mns). The possibility that both these changes partly result from presynaptic inhibition of Ia fibres projecting to Sol Mns and to interneurones mediating group I non-reciprocal inhibition is tested. Convergence of Ia fibres on these interneurones was deduced from evidence that reducing the excitatory effect of the extensor Ia fibres (by potentiation of their presynaptic inhibition) resulted in Ib disinhibition. Nociceptive-induced potentiation of Ia presynaptic inhibition was deduced from the following congruent results obtained by two independent methods: (1) depression of heteronymous Ia monosynaptic facilitation of the quadriceps muscle to Sol Mns; (2) potentiation of presynaptic inhibition of Sol Ia fibres evoked by mechanical activation of the tibialis anterior primary spindle afferents. It is concluded that nociceptive volleys arising from dorsal foot muscles facilitate the activity of interneurones intercalated in pathways responsible for presynaptic inhibition of Sol Ia fibres. It is also proposed that the same Ia presynaptic inhibition depresses the excitability of interneurones mediating group I non-reciprocal inhibition, thus resulting in Ib disinhibition of Sol Mns.
Brain Research 03/1999; 818(1):12-22. DOI:10.1016/S0006-8993(98)01253-0 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a previous paper it was shown that muscle nociceptive discharge depressed the activity of interneurones mediating group I non-reciprocal inhibition (or Ib interneurones) in humans [A. Rossi, B. Decchi, Changes in Ib heteronymous inhibition to soleus motoneurons during cutaneous and muscle nociceptive stimulation in humans, Brain Res. 774 (1997) 55-61.]. However, since nociceptive discharge depressed the size of the soleus H-reflex (by which Ib inhibition was tested) the question arises as to whether modification of motoneurone membrane conductance per se could depress the size of Ib inhibitory post-synaptic potentials. The results of the present study suggest that the contribution of motoneurone hyperpolarization to Ib disinhibition is negligible and that muscle nociceptive discharge actually depresses the activity of these pathways.
Brain Research 02/1999; 815(1):106-10. DOI:10.1016/S0006-8993(98)01111-1 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the effect of a tonic discharge of muscle nociceptive afferents on somatosensory evoked potentials (SEPs) in humans in response to stimulation of non-nociceptive afferents arising from the same muscle. Conditioning nociceptive muscle stimulation was achieved by local injection of 50 mg levo-ascorbic acid (in a volume of 0.3 ml) in the body of the extensor digitorum brevis muscle (EDB). The test stimulus for SEPs was an electrical pulse applied to the EDB nerve at an intensity below the motor threshold. The main finding was that tonic muscle nociceptive stimulation strongly depressed the middle-latency P60-N75 complex without modifying the size of the early P40-N50 complex of SEPs. Depression of the P60-N75 complex was correlated with the pain-induced loss of proprioception of the foot, making it plausible that this cortical complex reflects neuronal processes leading to perception.
[Show abstract][Hide abstract] ABSTRACT: Ipsi- and contralateral patterns of lower limb nociceptive reflex responses were studied in 6 normal subjects in free standing position. Once the position was stabilized, only ankle extensor muscles showed consistent tonic activity while ankle flexors and knee extensors and flexors were virtually silent. Reflex responses, elicited by painful electrical stimuli to the skin of the plantar and dorsal aspect of the foot, were recorded from ipsi- and contralateral quadriceps (Q), biceps femoris (Bic), tibialis anterior (TA) and soleus (Sol) muscles. Plantar foot stimulation evoked a large excitatory response in the ipsilateral TA at about 80 ms and a smaller responses in Bic and Q at 70 ms and 110 ms, respectively. Ipsilateral excitatory effects after dorsal foot stimulation consisted of a Bic response at about 75 ms. In addition to excitatory effects, both plantar and dorsal foot stimulation evoked long-lasting suppression of ipsilateral Sol background activity starting at about 60 ms. Contralaterally, the only nociceptive effects after plantar or dorsal foot stimulation were a small excitatory response of Sol at about 85 ms. Evidence is provided that only excitatory responses were contingent upon nociceptive volley. The main mechanical effects seen after plantar stimulation were dorsiflexion of the foot without loss of heel contact with the floor; no withdrawal response of the foot followed nociceptive dorsal stimulation. Our main conclusion is that only reflex nociceptive responses serving to avoid the stimulus without conflicting with limb support function are expressed. The mechanisms reconciling nociceptive action and postural function of the lower limbs are discussed.
Electroencephalography and Clinical Neurophysiology 01/1998; 105(6-105):484-489. DOI:10.1016/S0924-980X(97)00048-9
[Show abstract][Hide abstract] ABSTRACT: The effects of selective tonic cutaneous and muscle pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis to the soleus motoneurones were studied in five healthy human subjects. Tonic pain stimulation, monitored by a psychophysical method, was obtained by local injection of 60 mg levo-ascorbic acid (L-AS) in a volume of 0.3 ml. Nociceptive cutaneous and muscle stimulation of the dorsal foot produced opposite, long-lasting changes in heteronymous Ib pathways to soleus motoneurones: Ib facilitation during cutaneous stimulation was reversed by disinhibition during muscle stimulation. The time-course of these Ib changes strictly paralleled that of subjective pain sensation. On the contrary, when the same nociceptive stimuli were applied to the leg (at pretibial level), the differences between cutaneous and muscle pain disappeared and similar short-lasting phases of facilitation and inhibition of Ib activity were observed. It is concluded that tonic discharge of cutaneous and muscle nociceptive afferents arising from the foot have specific and opposite effects on Ib inhibitory pathways to ankle extensor motoneurones. These interactions between muscle and cutaneous nociceptive and Ib pathways may be used to change muscle synergies, thus contributing to the establishment of appropriate adaptive locomotor strategies during pain.
Brain Research 12/1997; 774(1-2-774):55-61. DOI:10.1016/S0006-8993(97)81687-3 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 1. Effects of conditioning motor volleys of increasing amplitude on antagonistic motor nuclei were tested at the wrist and elbow level in man. 2. The modifications of biceps, triceps, flexor carpi radialis (FCR) and extensor carpi radialis (ECR) motoneurone excitability were tested both in post-stimulus time histogram (PSTH) and rectified averaged EMG experiments. 3. Conditioning motor volleys were evoked in biceps, triceps, FCR and ECR muscles by electrical stimuli applied to the corresponding nerves. The intensity of the conditioning stimuli was systematically varied from an intensity just below motor threshold to one giving rise to a motor response equal to half of the maximal direct motor response (Mmax). 4. The effect of the injection of a cholinergist agonist, L-acetylcarnitine (L-Ac), on antagonistic conditioning motor volleys was tested for each motor nucleus. 5. Results obtained at the wrist and elbow level were strikingly different. Antagonistic motor volleys resulted in an early and long-lasting inhibition enhanced by L-Ac injection in wrist motor nuclei, while no modification was observed in elbow motor nuclei. 6. The characteristics of the early and long-lasting inhibition evoked in wrist motor nuclei by antagonistic motor volleys suggest that they are due to the activation of Renshaw cells by the conditioning motor volleys. 7. It is therefore concluded that these experiments provide further evidence that the interconnections between motoneurones, interneurones mediating reciprocal inhibition and Renshaw cells at the wrist level are different from those described elsewhere. Indeed, it has already been shown that the interneurones mediating reciprocal inhibition between FCR and ECR are not inhibited by Renshaw cells, and the results presented here suggest that FCR-coupled Renshaw cells inhibit ECR motoneurones and vice versa.
The Journal of Physiology 03/1997; 499 ( Pt 1)(1):267-82. DOI:10.1113/jphysiol.1997.sp021925 · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In six healthy subjects, the reflex responses of the tibialis anterior muscle (TA) to stimulation of the cutaneous afferents arising from plantar foot, were studied at rest and during different levels of steady voluntary contraction of the TA. At rest, the threshold of the response and the threshold of subjective pain sensation coincided. The mean latency of this TA nociceptive response was 84.7 ms. Steady voluntary contractions of the TA, which was increased progressively from 3% to 15% of the maximum voluntary contraction, produced a significant and parallel reduction in the threshold and latency of the response: at 15%, the mean latency was about 26 ms shorter than at rest and its threshold was about half (i.e. below the pain threshold). The conduction velocity of the afferents responsible for TA response at rest was within the range of A-delta pain afferents (mean 27.4 m/s), whereas during voluntary contraction it was within the A-beta fibre range (mean 45.1 m/s). This suggests that descending command makes the discharge of low-threshold, fast-conducting fibres sufficient for reflex activation of TA motoneurones (MNs). Central delay (about 4 ms) and MN recruitment order (according to the size principle) were found to be the same for both nociceptive and non-nociceptive TA reflex responses. Finally, experiments of spatial summation revealed an interaction between nociceptive and non-nociceptive inputs at a premotoneuronal level. It is therefore proposed that nociceptive and non-nociceptive cutaneous afferents arising from the foot sole use the same short-latency spinal pathway to contact TA MNs and that their relative contribution to its segmental activation is contingent upon descending command.
Brain Research 05/1996; 714(1-2):76-86. DOI:10.1016/0006-8993(95)01483-7 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The contribution of joint afferents to the response of cortical neurons in area 3a to mechanical stimulation of the contralateral hindlimb was evaluated in cats anesthetized with sodium pentobarbital and paralyzed with pancuronium bromide. The hindlimb projection to the pericruciate cortex was established by recording the evoked potentials to electrical stimulation of the sciatic nerve and some of its branches, the bicepssemitendinosus and the quadratus femoris. Out of 169 neurons, 63 responded exclusively to cutaneous stimuli (superficial), whereas the others could be activated by local pressure of hindlimb muscles and/or by joint rotation (deep). Deep neurons were classified as slowly adapting (SA) or rapidly adapting (RA) units. In the neurons responding exclusively to joint rotation, the site of the receptive field could not be identified with certainty. In 13 deep neurons, their firing was affected by rotation of multiple joints of the contralateral hindlimb. In an attempt to identify the source of activation of cortical neurons, partial denervations and muscle disconnections were performed in five animals to isolate and stimulate the hip capsule. In these preparations, in 14 of 15 cortical neurons the source of activation was localized in the periarticular muscles, with no response to mechanical stimulation of the joint capsule. Only one neuron (SA) could be selectively excited by punctate pressure on the hip capsule. Our results suggest that in neurons of area 3a of the cat, the information about the position of the femur relies mainly on muscle afferents.
Somatosensory and Motor Research 02/1996; 13(3-4):263-71. DOI:10.3109/08990229609052582 · 0.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effects of tonic pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis (GM) to the soleus (Sol) and to the quadriceps (Q) muscles were investigated in four healthy human subjects. Tonic pain stimulation was performed by subcutaneous injection of 0.5 mg levo-ascorbic acid or vitamin C (L-LAS) in a volume of 0.5 ml on the dorsal surface of the ipsilateral foot. The mean curve of L-AS-induced pain sensation showed a steep rising phase reaching maximum intensity at 2-3 min, followed by a slow decay phase lasting about 15-20 min. Between about 5 and 20 min after injection, there was evidence of pure pain stimulation due to chemical activation of free nerve endings. During this interval, significant potentiation of Ib inhibition from GM to both Sol and Q motoneurones was observed. The time-course of these Ib heteronymous changes paralleled that of subjective pain sensation. These findings demonstrate that nociceptive discharge modifies the gain of Ib heteronymous effects in humans. Since the man function of these Ib pathways is to coordinate activity of muscles operating at different joints, it is suggested that nociceptive input may change muscle synergies by selecting specific subpopulations of Ib interneurones, thus contributing to establish appropriate adaptive motor strategies.
Brain Research 12/1995; 700(1-2):164-72. DOI:10.1016/0006-8993(95)00947-O · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Interneurones mediating disynaptic inhibition from extensor to flexor carpi radialis muscles were characterized by pharmacological stimulation of Renshaw cells. It is, indeed, known that only Ia interneurones are blocked by recurrent inhibition. Renshaw cell potentiation, induced by intravenous administration of 2 g levo-acetylcarnitine, blocked Ia reciprocal inhibition from triceps to biceps muscles but not disynaptic inhibition from extensor to flexor carpi radialis muscles. It is concluded that the interneurones mediating this latter inhibition are not Ia interneurones. This kind of inhibition could be an example of a Ia non-reciprocal inhibitory pathway.
[Show abstract][Hide abstract] ABSTRACT: 1. In six human subjects standing without support, the reflex response of the tibialis anterior muscle (TA) was elicited by painful electrical stimulation (500 Hz, 20 ms) of the anterior sole of the foot and analysed by post-stimulus averages of rectified electromyography. The threshold intensity for the reflex response was very close to the subjective pain sensation (mean value, 1.05 times). Estimation of the afferent conduction velocity gave a mean value of 26.5 m s-1, suggesting that a contribution from A delta fibres was necessary to evoke the reflex response. The TA reflex response was then used as the pain test reflex. 2. Changes in the TA excitatory pain reflex response (elicited at 1.2 times the pain threshold) were investigated while the subjects maintained different postures in upright stance. Standing on the ipsilateral leg produced a significant decrease in the reflex response with respect to its value in symmetrical stance (standing on both legs), whereas a significant facilitation was observed when the subject was standing on the contralateral leg. A parallel depression of the response in both limbs was present when the subject maintained an upright stance with the lower limbs abducted. Thus, it was apparent that the TA pain responses decreased as the supporting function of the leg increased. 3. A significant inverse correlation between the load to which the limb was subjected and the size of the reflex response was observed in all subjects. We propose that the load to which the limb is subjected, measured from peripheral mechanoreceptors, is used as a measure of the current supporting function of the limb, on the basis of which the reflex is regulated.
The Journal of Physiology 01/1995; 481 ( Pt 2)(2):521-32. DOI:10.1113/jphysiol.1994.sp020460 · 5.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Presence of heteronymous recurrent inhibition in motoneurones (Mns) innervating the soleus muscle (Sol) was investigated following electrical stimulation of the nerve of gastrocnemius medialis muscle (GM). Sub-threshold electrical stimulation for alpha Mns produced short-lasting inhibition of the Sol, reflecting non-reciprocal group I inhibition. After increasing the intensity of stimulation above the motor threshold, a short-latency, long-lasting inhibition appeared superimposed on the group I inhibition. Its amount increased with the size of the conditioning motor response and after acute administration of L-acetylcarnitine. It is concluded that this long-lasting inhibition of the Sol Mns is due to the heteronymous activity of the GM-coupled Renshaw cells.
[Show abstract][Hide abstract] ABSTRACT: The recurrent inhibition of alpha motoneurons was studied in 8 mentally retarded subjects (age 16-35 years), six of whom also had non-pyramidal or extrapyramidal motor alterations, manifesting as rigid and inflexible voluntary and/or postural movements. Despite a similar degree of mental retardation (Raven spatial general intelligence test), the other 2 cases showed much more modest changes in motor behavior. At rest, recurrent inhibition on soleus motoneurons was normal in all patients. In the 6 cases exhibiting more severe motor abnormality, the changes in Renshaw cell excitability, which occur during postural or voluntary contractions in normal subjects, were not found. This expressed the lack of supraspinal influences on Renshaw cells in these patients. On the other hand, supraspinal modulating influences on Renshaw cells were virtually normal in the remaining 2 patients. The absence of excitability changes of recurrent inhibition to postural or voluntary movements is discussed in relation to the abnormality of motor behavior observed in these patients. In addition, since paralysis of adaptive changes of recurrent inhibition has so far only been described in spastic subjects, the present study demonstrates that the descending pathways, which control recurrent inhibition gain, are different from those which, when damaged, lead to spasticity. Finally, our results indicate that the changes in motor behavior often associated with mental retardation cannot be regarded merely as the consequence of defective motor learning.
Electroencephalography and Clinical Neurophysiology 01/1993; 85(6):419-24. DOI:10.1016/0168-5597(92)90056-H