Segmental Spinal Mechanisms Research Articles

A Re-evaluation of Whether Non-monosynaptic Homonymous H Reflex Facilitation Tests Propriospinal Circuits.

The C3–C4 propriospinal system is an important pathway mediating movement in cats; it contributes to movements in primates (including humans), and may have a role in recovery after lesion. Validated clinical tests of this system would find many applications, therefore we sought to test whether non-monosynaptic homonymous facilitation of the forearm flexor H reflex is mediated solely via a C3–C4 propriospinal pathway. In one anesthetized macaque monkey, median nerve stimulation elicited an H reflex in the flexor carpi radialis (FCR). Median nerve conditioning stimuli at sub-threshold intensities facilitated the H reflex, for inter-stimulus intervals up to 30 ms. Successive spinal surgical hemisections were then made. C2 lesion left the homonymous facilitation intact, suggesting mediation by spinal, not supraspinal pathways. Facilitation also remained after a second lesion at C5, indicating a major role for segmental (C7–C8) rather than propriospinal (C3–C4) interneurons. In separate experiments in five healthy human subjects, a threshold tracking approach assessed changes in peripheral axon excitability after conditioning stimulation. This was found to be enhanced up to 20 ms after the conditioning stimulus, and could partly, although not completely, underlie the H reflex facilitation seen. We conclude that homonymous facilitation of the H reflex in FCR can be produced by segmental spinal mechanisms, as well as by a supranormal period of nerve excitability. Unfortunately, this straightforward test cannot therefore be used for selective assessment of propriospinal circuits.

Homotopic reduction in laser-evoked potential amplitude and laser-pain rating by abdominal acupuncture.

The neural mechanism underlying the analgesic effect of acupuncture is largely unknown. We aimed at investigating the effect of abdominal acupuncture (AA) on the laser-evoked potential (LEP) amplitude and laser-pain rating to stimulation of body parts either homotopic or heterotopic to the treated acupoint. Laser-evoked potentials were recorded from 13 healthy subjects to stimulation of the right wrist (RW), left wrist (LW) and right foot (RF). LEPs were obtained before, during and after the AA stimulation of an abdominal area corresponding to the representation of the RW. Subjective laser-pain rating was collected after each LEP recording. The amplitude of the N2/P2 LEP component was significantly reduced during AA and 15min after needle removal to both RW (F=4.14, p=.02) and LW (F=5.48, p=.008) stimulation, while the N2/P2 amplitude to RF stimulation (F=0.94, p=.4) remained unchanged. Laser-pain rating was reduced during AA and 15min after needle removal only to RW stimulation (F=5.67, p=.007). Our findings showing an AA effect on LEP components to both the ipsilateral and contralateral region homotopic to the treated area, without any LEP change to stimulation of a heterotopic region, suggest that the AA analgesia is mediated by a segmental spinal mechanism. Although abdominal acupuncture has demonstrated to be effective in the reduction in laser-evoked potential (LEP) amplitude and laser-pain rating, the exact mechanism of this analgesic effect is not known. In the current study, we found that treatment of an area in the "turtle representation" of the body led to a topographical pattern of LEP amplitude inhibition that can be mediated by a segmental spinal mechanism.

Synergic control of a single muscle: The example of flexor digitorum superficialis.

We used the idea of synergic control and the framework of the uncontrolled manifold hypothesis to explore the synergic control of a single muscle. Individual motor units in flexor digitorum superficialis formed two-three groups (MU-modes) with parallel changes in firing frequency, robust over force-up and force-down segments. There were strong force-stabilizing synergies in the MU-mode space during accurate cyclical force production. The results show, for the first time, that the idea of synergic control is applicable to individual muscles. The results suggest that segmental spinal mechanisms, such as recurrent inhibition and stretch reflex, probably play a major role in the synergic control of action. In the present study, for the first time, we have used the idea of synergic control and the framework of the uncontrolled manifold (UCM) hypothesis to test two hypotheses: (i) individual motor units are organized into stable groups (MU-modes) with parallel scaling of firing rates with changes in the muscle force, and (ii) the gains of MU-mode involvement co-vary to stabilize the desired force magnitude. Young healthy subjects performed accurate cyclical force tracing tasks at 1Hz by pressing with intermediate phalanges; only one finger was instructed to produce force at a time. Surface electromyographic signal from flexor digitorum superficialis was recorded and used to identify individual motor units and their firing frequencies. Principal component analysis with rotation and factor extraction was used to identify MU-modes, which showed similar compositions over the force-up and force-down task segments. Inter-cycle variance analysis in the MU-mode space confirmed the existence of strong synergies stabilizing finger force. There were no synergies stabilizing MU-mode magnitude in the space of individual motor units. This is the first application of the UCM framework to the neural control of a single muscle. It extends the applicability of this approach to analysis of individual muscles. We discuss the importance of the findings for the idea of hierarchical control and the notion of muscle compartments. The results suggest that segmental spinal mechanisms, such as recurrent inhibition and stretch reflex, probably play a major role in the synergic control of action.

Changes in the nociceptive response to thermal stimulation in rats following administration of N-terminal analogs of the adrenocorticotropic hormone

Melanocortins (MCs) are an increasingly studied class of regulatory peptides exerting a wide range of biological effects. All naturally occurring MCs share a His-Phe-Arg-Trp fragment (HFRW) corresponding to the sequence of amino acid residues 6–9 of the adrenocorticotropic hormone (ACTH6-9), which is also a central active component of ACTH. Attaching the Pro-Gly-Pro (PGP) sequence to the C-end of the peptide extends the duration of the peptide’s effect. The aim of this study was to investigate the effects of ACTH6-9-PGP (HFRWPGP) on the spinal and supraspinal mechanisms involved in the nociceptive response in rats and to compare them to those of its structural analog ACTH4-7-PGP (MEHFPGP). ACTH6-9-PGP effects were studied following the intraperitoneal administration of the peptide at doses 0.5, 1.5, 5, 15, 50, 150, or 450 μg/kg 15 minutes before the hot plate and tail flick tests. ACTH4-7-PGP effects were studied under the same conditions at the following doses: 50, 150 and 450 μg/kg. We found that ACTH6-9-PGP administered intraperitoneally at 5 or 150 μg/kg induced a pronounced reduction in pain sensitivity 15 and 45 minutes after the injection (p = 0.04); this effect was implemented via supraspinal mechanisms. In the tail flick test, 150 μg/kg ACTH6-9-PGP increased pain sensitivity, with the participation of segmental spinal mechanisms (p = 0.04). ACTH4-7-PGP did not have any effect on the studied mechanisms of pain sensitivity. Thus, unlike ACTH4-7-PGP, ACTH6-9-PGP can both increase pain sensitivity and exert an analgesic effect.

Hydrotherapy in nervous system diseases

SUMMARY
 
 Hydrotherapy is one method used in the rehabilitation treatment of various diseases, including diseases of the nervous system with a positive result. It is used in many exercise programs. It has been shown that hydrotherapy reduces the clinical symptoms of the nervous system diseases, reduces pain and improves quality of life. The mechanism of action of hydrotherapy is omnidirectional; among other things, it has a positive effect on segmental spinal mechanisms, induces muscle relaxation, affects the activity of the autonomic nervous system. The aim of the work was a review of the literature on hydrotherapy in nervous system diseases.

The rostroventromedial medulla is engaged in the effects of spinal cord stimulation in a rodent model of neuropathic pain

The neurobiological mechanisms underlying the suppression of neuropathic pain by spinal cord stimulation (SCS) are still incompletely known. The present study aims at exploring whether the descending pain control system in the rostroventromedial medulla (RVM) exerts a role in the attenuation of neuropathic pain by SCS. Experiments were performed in the rat spared nerve injury (SNI) pain model. The effects of SCS on neuronal activity of pronociceptive ON-like, antinociceptive OFF-like, and neutral cells, including 5-HT-like cells, in the RVM were analyzed in SCS responding and SCS non-responding SNI animals as well as in naïve controls. Decreased spontaneous activities in OFF-like cells and increased spontaneous activities in ON-like cells were observed in SNI animals, whereas the spontaneous activities of 5-HT-like and neutral cells were unchanged. SCS produced a prominent increase in the discharge of OFF- and 5-HT-like cells in SCS responding, but not in non-responding SNI animals or controls. Discharge rates of ON-like and neutral cell were not affected by SCS. In awake SNI animals, microinjection of a GABAA receptor agonist, muscimol, into the RVM significantly attenuated the antihypersensitivity effect induced by SCS while a non-selective opioid receptor antagonist, naltrexone, was ineffective.It is concluded that SCS may shift the reciprocal inhibitory and facilitatory pain modulation balance controlled by the RVM in favor of inhibition. This increase in the descending antinociceptive effect operates in concert with segmental spinal mechanisms in producing pain relief.

Spinal segmental and supraspinal mechanisms underlying the pain-relieving effects of spinal cord stimulation: An experimental study in a rat model of neuropathy

Spinal cord stimulation (SCS) may alleviate certain forms of neuropathic pain; its mechanisms of action are, however, not fully understood. Previous studies have mainly been focused onto segmental spinal mechanisms, though there is evidence indicating a supraspinal involvement. This study aims to evaluate the relative importance of segmental and supraspinal mechanisms related to the activation of the dorsal columns (DCs).Rats were used to induce the spared nerve injury neuropathy and simultaneously subjected to chronic bilateral DC lesions at the C6–C8 level. Two pairs of miniature electrodes were implanted in each animal, with a monopolar system placed in the dorsal epidural space at a low thoracic level (below lesion) and a bipolar system placed onto the dorsal column nuclei (above lesion). Stimulation (50Hz, 0.2ms, 2–4V, 5min) was applied via either type of electrodes, and tests for sensitivity to tactile and thermal stimuli were used to assess its inhibitory effects. Various receptor antagonists {bicuculline (GABAA), saclofen (GABAB), ketanserine (5HT2), methysergide (5HT1–2), phentolamine (α-adrenergic), propranolol (β-adrenergic), sulpiride (D2/D3 dopamine) or saline were injected prior to the SCS. Rostral and caudal stimulations produced a comparable inhibition of neuropathic manifestations, and these effects were attenuated by about 50% after DC lesions. Pretreatment with the various receptor antagonists differentially influenced the effects of rostral and caudal stimulation.Our findings suggest that both supraspinal and segmental mechanisms are activated by SCS, and that in this model with DC lesions, rostral and caudal stimulations may activate different synaptic circuitries and transmitter systems.

Spinal cord stimulation of dorsal columns in a rat model of neuropathic pain: Evidence for a segmental spinal mechanism of pain relief

Although spinal cord stimulation (SCS) of the dorsal columns is an established method for treating chronic neuropathic pain, patients still suffer from a substantial level of pain. From a clinical perspective it is known that the location of the SCS is of pivotal importance, thereby suggesting a segmental spinal mode of action. However, experimental studies suggest that SCS acts also through the modulation of supraspinal mechanisms, which might suggest that the location is unimportant. Here we investigated the effect of the rostrocaudal location of SCS stimulation and the effectiveness of pain relief in a rat model of chronic neuropathic pain. Adult male rats (n = 45) were submitted to a partial ligation of the sciatic nerve. The majority of animals developed tactile hypersensitivity in the nerve lesioned paw. All allodynic rats were submitted to SCS (n = 33) for 30 minutes (f = 50 Hz; pulse width 0.2 ms). In one group (n = 16) the electrodes were located at the level where the injured sciatic nerve afferents enter the spinal cord (T13), and in a second group (n = 17) the electrodes were positioned at more rostral levels (T11) as verified by X-ray. A repositioning experiment of electrodes from T12 to T13 was performed in 2 animals. Our data demonstrate that SCS of the dorsal columns at the level where the injured fibers enter the spinal cord dorsal horn result in a much better pain-relieving effect than SCS at more rostral levels. From this we conclude that SCS in treatment of neuropathic pain acts through a segmental spinal site of action.

Gating of the micturition reflex by tonic activation of bladder cold receptors in the cat

To determine whether C afferents can modify the gating of the Adelta micturition reflex in order to identify the neuronal site of interaction of the two afferent systems. Adult female cats, anaesthetized with alpha-chloralose, had their bladder and urethra catherized through a slit in the proximal urethra. Micturition threshold volume was assessed by cystometry and bladder efferent activity recorded simultaneously. The bladder was filled at a slow rate (1.2-3.5 ml/min) with either body-warm saline (control) or menthol solution (0.06 mM) or by cold saline (4 degrees C). Of 14 trial sessions in 5 animals, the threshold volume of the Adelta micturition reflex was consistently reduced by menthol infusions from a control median (md) value of 16.8 to 10.2 ml (P < 0.01). The threshold pressure was also somewhat decreased from md 0.7 to 0.5 kPa (P < 0.05), while the peak pressure or pressure slope did no differ in two situations. Similar results were obtained with slow cold infusions into the bladder (nine sessions in three animals). The threshold volume decreased from md 19.8 to 17.4 ml (P < 0.05). The bladder reflex response to slow menthol or cold infusions had the typical features of an Adelta micturition reflex in that the efferent activity was largely abolished by the bladder Adelta mechanoreceptor unloading. Gradual tonic activation of bladder cold receptors lowers the threshold volume of the ordinary Adelta micturition, pointing to a segmental spinal mechanism for the gating of the micturition reflex.

Hypoalgesia following intrathecal morphine: a segmental dependent effect

The onset phase of hypoalgesia, following intrathecal morphine, was assessed by experimental argon laser-induced pain. A dose of 0.4 mg morphine was injected pre-operatively at the L3-L4 level into nine patients. The thresholds to laser-induced pain and pain-evoked brain potentials were monitored for 2 h at the S1, L1, and C7 dermatomes. Hypoalgesia was detected at the S1 and L1 dermatomes after 5 and 15 min, respectively. No hypoalgesic effect was found at C7. This indicates that hypoalgesia was caused predominantly by segmental spinal mechanisms during the onset phase, and not by a general widespread effect. No latency changes (conduction delay) of the brain potentials evoked from the hypoalgesic dermatomes were found. Cutaneous pain, induced experimentally by laser stimulation, has the advantage of being quantitative and is useful to assess the onset and the segmental spread of hypoalgesia.

Propriospinal control of last order interneurones of spinal reflex pathways in the cat

In studies from our laboratory on the supraspinal control of segmental spinal mechanisms, the problem has occasionally arisen as to whether some segmental effects evoked by stimulation of a supraspinal tract were due to activation of long propriospinal neurones. For this and other reasons it became necessary to obtain more information about long propriospinal neurones, not only with respect to their segmental origin, the trajectory of their axons and their synaptic activation, but also regarding their effects on segmental mechanisms. To analyze segmental synaptic effects evoked by propriospinal fibres we chose to stimulate the axons directly at the low thoracic level, and limited ourselves to effects on motoneurones and last order interneurones in spinal reflex pathways. In this report it will be shown that propriospinal fibres terminate on some interneurones which project directly to motoneurones, and that these iriterneurones are interposed in two well defined segmental reflex pathways. Both conclusions are based on intracellular records of postsynaptic potentials (PSPs) evoked in motoneurones (in L6-SI spinal segments) by stimulation ofpropriospinal and peripheral nerve fibres, and on an analysis of interactions between effects evoked from these two sources. The experiments were performed on 8 cats anaesthetized with chloralose, in which the spinal cord had been hemisected at a high cervical (C3) level, 2-13 weeks before, in order to produce degeneration of fibres of supraspinal origin. Propriospinal fibres originating between high cervical and low thoracic segments were stimulated at Thl 1. Since our attention was focussed on the long propriospinal pathways which descend in the middle of the lateral funicle 9, we transected the following fibre systems caudal to the level of stimulation: the dorsal column, the contralateral spinal half, the ipsilateral superficial dorsomedial part of the lateral funicle (including the spinocervical tract), the ipsilateral ventral funicle and the very ventral part of the lateral funicle. Despite these lesions it cannot be excluded that some segmental effects evoked by stimulation at Th 11 may be collateral to antidromic activation of ascending axons. To investigate this possibility, control experiments were made in animals after a chronic hemisection of the spinal cord at a low thoracic (Thl0) level. This lesion

Neural mechanisms of the chloralose jerk with special reference to its relationship with the spino-bulbo-spinal reflex.

1. Experiments were performed on 26 adult cats under chloralose anesthesia, in order to investigate whether a relationship exists between the neural mechanisms of the chloralose jerky reaction and the spino-bulbo-spinal (SBS) reflex.2. A single tactile stimulation to the skin over the body yielded early and late responses from the spinal motor nerves and muscles.3. The early one, which was apparently due to the segmental spinal mechanisms, was not concerned in the chloralose jerky muscular reaction.4. The late response may be related to the chloralose jerky muscular reaction. Characteristics of the late response may be summarized as follows: a) On weak stimulation, the late response was recorded mainly from flexor motor nerves. b) The late response was obtained from the spinal ventral roots at different levels along the spinal cord. Its latency became steadily shorter as one recorded from segments closer to the brainstem. c) The conduction velocity of the descending pathway in the late response was about 30m/sec. d) After spinal transection, the late response was completely abolished. e) Pentobarbital sodium anesthesia affected the late response at dosage levels of about 3mg/kg.5. Above noted observations were almost the same as those of the SBS reflex This suggests that some part of the neural mechanisms of the chloralose jerky muscular reaction may be the same as those of the SBS reflex.