Post-activation depression of Soleus stretch reflexes in healthy and spastic humans

Grey, Michael J.; Klinge, K; Crone, C; Lorentzen, Jakob; Biering‐Sørensen, Fin; Ravnborg, Mads; Nielsen, Jens Bo

doi:10.1007/s00221-007-1142-6

Cited by 121 publications

(102 citation statements)

References 33 publications

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“…5, B and D). Reduced PAD has been reported previously in pathological and spastic conditions (Grey et al 2008;Nielsen et al 1993Nielsen et al , 1995. This impairment is also suggested to be correlated with spasticity and motor impairment (Burke et al 2013).…”

Section: Discussionsupporting

confidence: 66%

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Characteristics of preceding Ia activity on postactivation depression in health and disease

Tahayori

Koceja

2015

Journal of Neurophysiology

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Previous activation of the soleus Ia afferents causes a depression in the amplitude of the H-reflex. This mechanism is referred to as postactivation depression (PAD) and is suggested to be presynaptically mediated. With the use of a paired reflex depression paradigm (eliciting two H-reflexes with conditioning-test intervals from 80 ms to 300 ms), PAD was examined in a group of healthy individuals and a group of hemiplegic patients. Healthy individuals showed substantial depression of the test H-reflex at all intervals. Although the patient group showed substantially less depression at all intervals, increasing the interval between the two reflexes sharply reduced the depression. In a separate experiment, we varied the size of the conditioning H-reflex against a constant test H-reflex. In healthy individuals, by increasing the size of the conditioning H-reflex, the amplitude of the test H-reflex exponentially decreased. In the patient group, however, this pattern was dependent on the conditioning-test interval; increasing the size of the conditioning H-reflex caused an exponential decrease in the size of the test reflex at intervals shorter than 150 ms. This pattern was similar to that of healthy individuals. However, conducting the same protocol at a longer interval (300 ms) in these patients resulted in an abnormal pattern (instead of an exponential decrease in the size of the test reflex, exaggerated responses were observed). Fisher discriminant analysis suggested that these two patterns (which differed only in the timing between the two stimuli) were substantially different from each other. Therefore, it is suggested that the abnormal pattern of PAD in hemiplegic stroke patients could be a contributing factor for the pathophysiology of spasticity.

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Section: Discussionsupporting

confidence: 66%

“…It is known that this depression is substantially reduced in spastic patients and patients with multiple sclerosis and spinal cord injuries (Grey et al 2008;Nielsen et al 1995). Evidence also exists to suggest that the impairment in PAD contributes to the pathophysiology of spasticity and also correlates with hyperreflexia (Aymard et al 2000).…”

mentioning

confidence: 99%

Characteristics of preceding Ia activity on postactivation depression in health and disease

Tahayori

Koceja

2015

Journal of Neurophysiology

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“…4 A-C). Reduction of the RDD is a reliable correlate of spasticity after SCI (10,29,30). The down-regulation of KCC2 accounts, at least in part, for this reduction (10).…”

Section: Resultsmentioning

confidence: 99%

Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

Bos

Sadlaoud

Boulenguez

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

159

172

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In healthy adults, activation of γ-aminobutyric acid (GABA) A and glycine receptors inhibits neurons as a result of low intracellular chloride concentration ([Cl -] i ), which is maintained by the potassium-chloride cotransporter KCC2. A reduction of KCC2 expression or function is implicated in the pathogenesis of several neurological disorders, including spasticity and chronic pain following spinal cord injury (SCI). Given the critical role of KCC2 in regulating the strength and robustness of inhibition, identifying tools that may increase KCC2 function and, hence, restore endogenous inhibition in pathological conditions is of particular importance. We show that activation of 5-hydroxytryptamine (5-HT) type 2A receptors to serotonin hyperpolarizes the reversal potential of inhibitory postsynaptic potentials (IPSPs), E IPSP , in spinal motoneurons, increases the cell membrane expression of KCC2 and both restores endogenous inhibition and reduces spasticity after SCI in rats. Up-regulation of KCC2 function by targeting 5-HT 2A receptors, therefore, has therapeutic potential in the treatment of neurological disorders involving altered chloride homeostasis. However, these receptors have been implicated in several psychiatric disorders, and their effects on pain processing are controversial, highlighting the need to further investigate the potential systemic effects of specific 5-HT 2A R agonists, such as (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2). ] i (depolarizing shift of the chloride equilibrium potential, E Cl ) dramatically compromises the inhibitory control of firing rate and excitatory inputs (5-7). Given the role of KCC2 in regulating the strength of inhibitory synaptic transmission, identifying tools that may increase KCC2 function and, hence, restore endogenous inhibition in pathological conditions is of particular importance.Spasticity is a disabling complication affecting individuals with spinal cord injury (SCI) and is characterized by a velocity-dependent increase in muscle tone resulting from hyperexcitable stretch reflexes, spasms, and hypersensitivity to normally innocuous sensory stimulations (8, 9). Down-regulation of KCC2 after SCI in rats is implicated in the development of spasticity (10) and chronic pain (11,12). Notably, the expression of KCC2 in the motoneuron membrane is reduced, and, concomitantly, the density of cytoplasmic clusters is higher, suggesting that the surface stability of the transporter is reduced in these pathological conditions (10).Mounting evidence indicates that phosphorylation of KCC2 in the C-terminal intracellular domain dynamically regulates its activity and surface expression (1). In particular, phosphorylation by protein kinase (PK)C, enhances KCC2 activity and reduces endocytosis (13). Interestingly, activation of 5-hydroxytryptamine type 2 receptors (5-HT 2 Rs) to serotonin stimulates PKC and strengthens the left-right alternation of motor bursts observed during locomotion (14-16), which rely on reciprocal inhibition (17, 18). ...

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“…The lack of attenuation of the PRM reflexes elicited by 2-Hz SCS may have resulted from the multiroot input provided by SCS together with alterations in the spinal circuits' excitability after SCI (Grey et al 2008;Ishikawa et al 1966). At such stimulation frequency, the net results of inhibition and excitation may have evened each other out.…”

Section: Discussionmentioning

confidence: 99%

Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

Hofstoetter

Danner

Freundl

et al. 2015

Journal of Neurophysiology

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Hofstoetter US, Danner SM, Freundl B, Binder H, Mayr W, Rattay F, Minassian K. Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord. J Neurophysiol 114: 400 -410, 2015. First published April 22, 2015 doi:10.1152/jn.00136.2015.-In individuals with motor-complete spinal cord injury, epidural stimulation of the lumbosacral spinal cord at 2 Hz evokes unmodulated reflexes in the lower limbs, while stimulation at 22-60 Hz can generate rhythmic burstlike activity. Here we elaborated on an output pattern emerging at transitional stimulation frequencies with consecutively elicited reflexes alternating between large and small. We analyzed responses concomitantly elicited in thigh and leg muscle groups bilaterally by epidural stimulation in eight motor-complete spinal cord-injured individuals. Periodic amplitude modulation of at least 20 successive responses occurred in 31.4% of all available data sets with stimulation frequency set at 5-26 Hz, with highest prevalence at 16 Hz. It could be evoked in a single muscle group only but was more strongly expressed and consistent when occurring in pairs of antagonists or in the same muscle group bilaterally. Latencies and waveforms of the modulated reflexes corresponded to those of the unmodulated, monosynaptic responses to 2-Hz stimulation. We suggest that the cyclical changes of reflex excitability resulted from the interaction of facilitatory and inhibitory mechanisms emerging after specific delays and with distinct durations, including postactivation depression, recurrent inhibition and facilitation, as well as reafferent feedback activation. The emergence of large responses within the patterns at a rate of 5.5/s or 8/s may further suggest the entrainment of spinal mechanisms as involved in clonus. The study demonstrates that the human lumbosacral spinal cord can organize a simple form of rhythmicity through the repetitive activation of spinal reflex circuits.

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Post-activation depression of Soleus stretch reflexes in healthy and spastic humans

Cited by 121 publications

References 33 publications

Characteristics of preceding Ia activity on postactivation depression in health and disease

Characteristics of preceding Ia activity on postactivation depression in health and disease

Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

Periodic modulation of repetitively elicited monosynaptic reflexes of the human lumbosacral spinal cord

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