Spinal cord transection produces a long‐term increase in GABA<sub>B</sub> binding in the rat substantia gelatinosa

Bianchi, Gregory D.; Penn, Richard D.

doi:10.1002/syn.890140404

Cited by 4 publications

(3 citation statements)

References 30 publications

(37 reference statements)

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“…baclofen in rats with a spinal compression was greater than that of muscimol, which was also the case in peripheral injury pain models (Dirig and Yaksh, 1995; Hwang and Yaksh, 1997). The potency and efficacy of baclofen could be due to an increase in spinal GABA B binding sites following SCI (Kroin et al, 1993). The finding of i.t.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Denervation supersensitivity occurs in the spinal cord as well as in the brain. [42][43][44][45][46] Proposed mechanisms of denervation supersensitivity include: (1) reduced excitatory neurotransmitter reuptake, (2) increased synthesis and insertion of 48 and (4) altered synthesis and composition of receptor subunits. [48][49][50] All of these could occur quickly and be consistent with reflex change at 1-3 days.…”

Section: Phase 2: Initial Reflex Return (1-3 Days)mentioning

confidence: 99%

Spinal shock revisited: a four-phase model

et al. 2004

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Spinal shock has been of interest to clinicians for over two centuries. Advances in our understanding of both the neurophysiology of the spinal cord and neuroplasticity following spinal cord injury have provided us with additional insight into the phenomena of spinal shock. In this review, we provide a historical background followed by a description of a novel fourphase model for understanding and describing spinal shock. Clinical implications of the model are discussed as well.

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“…Denervation supersensitivity is defined as increased neuronal firing in response to a neurotransmitter [46]. This phenomenon has been shown to occur in both the peripheral (PNS) and central (CNS) nervous systems, including the brain and the spinal cord [47][48][49][50][51]. The proposed mechanisms involves upregulation of mRNA transcription and protein translation that begins within hours and peaks within days post-SCI, which is within the time scale of empirically observed changes [52].…”

Section: Phase IImentioning

confidence: 99%

Spinal Shock: Differentiation from Neurogenic Shock and Key Management Approaches

Conti¹,

Yellapu²,

Sweeney³

et al. 2020

Clinical Management of Shock - The Science and Art of Physiological Restoration

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The conceptual differentiation of spinal and neurogenic shock tends to be misunderstood among clinicians. In order to better illustrate the differences in definition, presentation, and development of spinal shock (SS) from neurogenic and other forms of shock, we present herein a clinically relevant summary of typical characteristics of SS. First described in the eighteenth century, the continued investigation into the disease process and the response of neural structures to spinal cord trauma have led to a more complete description and understanding. We will begin in the first part of the chapter describing the etiology of SS, including a working definition, as it pertains to complete spinal cord injuries (SCIs). This is followed by the summary of pathophysiology and clinical presentations associated with each clinical phase of SS. Finally, we explore treatment options and considerations as they relate to incomplete SCI. We hope that by presenting a clear and well-delineated overview of SS, we will allow the clinician to better understand and more accurately predict the evolution of this process. This, in turn, should facilitate the ability to deliver better care for the patient.

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Spinal cord transection produces a long‐term increase in GABA_B binding in the rat substantia gelatinosa

Cited by 4 publications

References 30 publications

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

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

Spinal shock revisited: a four-phase model

Spinal Shock: Differentiation from Neurogenic Shock and Key Management Approaches

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Spinal cord transection produces a long‐term increase in GABAB binding in the rat substantia gelatinosa

Cited by 4 publications

References 30 publications

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

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

Spinal shock revisited: a four-phase model

Spinal Shock: Differentiation from Neurogenic Shock and Key Management Approaches

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Product

Resources

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Spinal cord transection produces a long‐term increase in GABA_B binding in the rat substantia gelatinosa