Traditional pharmacological treatments for spasticity part II: General and regional treatments

Graciès, Jean-Michel; Nance, Patricia W.; Elovic, Elie P.; McGuire, John R.; Simpson, David M.

doi:10.1002/(sici)1097-4598(1997)6+<92::aid-mus7>3.0.co;2-e

Cited by 184 publications

(29 citation statements)

References 86 publications

(131 reference statements)

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“…We believe that a comparable pharmacotherapeutic approach should be considered in the clinical management of acute and chronic itch. Most importantly, as sedation is the major cause for discontinuing baclofen treatment in patients 42 , it is particularly significant that a synergistic combination of very low doses of baclofen and subthreshold doses of other GABA agonists retain profound antipruritic effects, without concomitant sedation.…”

Section: Resultsmentioning

confidence: 99%

Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis

Cevikbas

Bráz²,

Wang³

et al. 2017

Journal of Allergy and Clinical Immunology

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Background Despite recent insights into the pathophysiology of acute and chronic itch, chronic itch remains an often intractable condition. Among major contributors to chronic itch is dysfunction of spinal cord GABAergic inhibitory controls. Objective To test the hypothesis that selective GABA agonists as well as cell transplant-derived GABA are antipruritic against acute itch and in a transgenic mouse model of atopic dermatitis produced by overexpression of the TH2 cell-associated cytokine, IL-31 (IL-31Tg mice). Methods We injected wild-type and IL-31Tg mice with combinations of GABA-A (muscimol) or GABA-B (baclofen) receptor agonists 15–20 min prior to injection of various pruritogens (histamine, chloroquine or endothelin-1) and recorded spontaneous scratching before and after drug administration. We also tested the antipruritic properties of intraspinal transplantation of precursors of GABAergic interneurons in the IL-31Tg mice. Results Systemic muscimol or baclofen are antipruritic against both histamine-dependent and independent pruritogens, but the therapeutic window using either ligand alone was very small. In contrast, combined subthreshold doses of baclofen and muscimol produced a significant synergistic antipruritic effect, with no sedation. Finally, transplant-mediated long term enhancement of GABAergic signaling not only reduced spontaneous scratching in the IL-31Tg mice but also dramatically resolved the associated skin lesions. Conclusion Although additional research is clearly needed, existing approved GABA agonists should be considered in the management of chronic itch, notably atopic dermatitis.

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Section: Resultsmentioning

confidence: 99%

Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis

Cevikbas

Bráz²,

Wang³

et al. 2017

Journal of Allergy and Clinical Immunology

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“…The only currently used antispastic that directly affects the excitability of the motoneuron (site 2, Figure 12) is cyproheptadine (Nance, 1994; Gracies et al, 1997); however, it lacks regulatory approval for this use. Cyproheptadine is as effective in reducing excessive muscle activity (17% reduction in Ashworth scores) compared to clonidine (22%) and baclofen (22%) (Nance, 1994), although this was only tested in 25 participants.…”

Section: Treatments For Spasticity and Recovery Of Motoneuron Functionmentioning

confidence: 99%

“…Cyproheptadine is as effective in reducing excessive muscle activity (17% reduction in Ashworth scores) compared to clonidine (22%) and baclofen (22%) (Nance, 1994), although this was only tested in 25 participants. Associated with the anti-histamine and anti-cholinergic properties of cyproheptadine were side effects such as CNS depression, dry mouth, appetite stimulation and thus, the potential for weight gain (Gracies et al, 1997). Despite these side effects, at low doses (12 mg/day) cyproheptadine decreased involuntary muscle spasms and clonus to improve residual walking function in participants with incomplete SCI (Wainberg et al, 1990).…”

Section: Treatments For Spasticity and Recovery Of Motoneuron Functionmentioning

confidence: 99%

“…While CNS depression may occur with dantrolene sodium, it is less severe than other oral antispastics (Watanabe, 2009; Lapeyre et al, 2010). Despite the reduction in reflexes, dantrolene sodium is not commonly prescribed for SCI spasticity likely because it produces generalized muscle weakness (Adams and Hicks, 2005) and can result in hepatotoxicity (Gracies et al, 1997). …”

Section: Treatments For Spasticity and Recovery Of Motoneuron Functionmentioning

confidence: 99%

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Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

D’Amico

Condliffe

Martins

et al. 2014

Front. Integr. Neurosci.

104

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The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI.

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“…Although systemic treatment with NMDA receptor antagonists and GABA receptor agonists have demonstrated efficacy in experimental neuropathic SCI pain, adverse side-effects induce muscle weakness, sedation and psychomimetic effects (Gracies et al, 1997; Hama and Sagen, 2007; Hao et al, 1991; Max et al, 1995; Xu et al, 1993). As an alternative, drugs could be intrathecally (i.t.)…”

Section: Introductionmentioning

confidence: 99%

Combinations of intrathecal gamma-amino-butyrate receptor agonists and N-methyl-d-aspartate receptor antagonists in rats with neuropathic spinal cord injury pain

Hama

Sagen

2012

European Journal of Pharmacology

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Underlying below-level cutaneous hypersensitivity observed following spinal cord injury (SCI) is a concurrent loss of inhibition with an increase in excitation in the spinal dorsal horn. Thus, a dual pharmacological approach, increasing spinal γ-aminobutyrate (GABA) inhibition and decreasing N-methyl-D-aspartate (NMDA) receptor-mediated excitation, could be more beneficial than either approach alone. The current study evaluated the antinociceptive effects of lumbar intrathecal (i.t.) administration of GABA receptor agonists and NMDA receptor antagonists alone and in combination in rats with neuropathic SCI pain. Rats developed markedly decreased hind paw withdrawal thresholds following an acute thoracic spinal cord compression, indicative of below-level hypersensitivity. Separately, i.t. GABAA receptor agonist muscimol and GABAB receptor agonist baclofen demonstrated dose-dependent antinociception, whereas i.t. NMDA receptor antagonist ketamine and the endogenous peptide [Ser1]histogranin, a putative NMDA receptor antagonist, demonstrated no efficacy. The combination of baclofen and ketamine resulted in a supra-additive (synergistic) antinociception whereas the combinations with muscimol were merely additive. Intrathecal pretreatment with the GABAB receptor antagonist CGP 35348 prevented the antinociceptive effect of the baclofen and ketamine combination. The data indicate that blocking spinal NMDA receptors alone is not sufficient to ameliorate SCI hypersensitivity, whereas a combined approach, simultaneous activation of spinal GABAB receptors and NMDA receptors blockade with ketamine, leads to significant antinociception. By engaging diverse pain modulating systems at the spinal level, combination drug treatment may be a useful approach in treating neuropathic SCI pain.

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Traditional pharmacological treatments for spasticity part II: General and regional treatments

Cited by 184 publications

References 86 publications

Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis

Synergistic antipruritic effects of gamma aminobutyric acid A and B agonists in a mouse model of atopic dermatitis

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

Combinations of intrathecal gamma-amino-butyrate receptor agonists and N-methyl-d-aspartate receptor antagonists in rats with neuropathic spinal cord injury pain

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