The role of α2-agonists in neurosurgery

Cormack, J.; Orme, RM; Costello, T.G.

doi:10.1016/j.jocn.2004.06.008

Cited by 77 publications

(65 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole monohydrochloride) is a short acting, potent and highly selective a 2 -adrenergic receptor agonist, and used as a sedative, anxiolytic, analgesic and sympatholytic drug. It induces sedation by acting on the a 2 -adrenergic receptors in the locus ceruleus [9]. It also produces analgesia by stimulating a 2 -adrenergic receptors in the spinal cord [35].…”

Section: Introductionmentioning

confidence: 99%

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

et al. 2009

View full text Add to dashboard Cite

The aim of this experimental study was to investigate the possible protective effect of dexmedetomidine (DEX) on traumatic spinal cord injury (SCI). Twentytwo New Zealand rabbits were divided into three groups: sham (no drug or operation, n = 6), Control [SCI ? single dose of 1 mL saline intraperitoneally (i.p), after trauma; n = 8] and DEX (SCI ? 1 lg/kg dexmedetomidine in 1 mL, i.p, after trauma, n = 8). Laminectomy was performed at T10 and balloon angioplasty catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated by an independent observer according to the Tarlov scoring system. Blood, cerebrospinal fluid (CSF), tissue samples from spinal cord were taken for biochemical and histopathological evaluations. After 4 h of SCI, all animals in control or DEX treated groups became paraparesic. On the other hand, 24 h after SCI, partial improvements were observed in both control and DEX treated groups. Traumatic SCI leads to increase in the lipid peroxidation and decreases enzymatic or nonenzymatic endogenous antioxidative defense systems. Again, SCI leads to apoptosis in spinal cord. DEX treatment slightly prevented lipid peroxidation and augmented endogenous antioxidative defense systems in CSF or spinal cord tissue, but failed to prevent apoptosis or neurodeficit after traumatic SCI. Therefore, it could be suggested that treatment with dexmedetomidine does not produce beneficial results in SCI.

show abstract

Section: Introductionmentioning

confidence: 99%

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Studies on genetically engineered mice made null or mutant for the ␣ 2A AR have revealed that this subtype mediates the therapeutic effects of ␣ 2 -adrenergic agents on blood pressure, pain perception, volatile anesthetic sparing, analgesia, and working memory enhancement (16 -18). Two classic ␣ 2 -ligands, clonidine and guanfacine, have been widely used to treat hypertension (19), attention deficit and hyperactivity disorder (20), and to elicit analgesia (19,21) …”

mentioning

confidence: 99%

Epitope-tagged Receptor Knock-in Mice Reveal That Differential Desensitization of α2-Adrenergic Responses Is because of Ligand-selective Internalization

Zhang

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Although ligand-selective regulation of G protein-coupled receptor-mediated signaling and trafficking are well documented, little is known about whether ligand-selective effects occur on endogenous receptors or whether such effects modify the signaling response in physiologically relevant cells. Using a gene targeting approach, we generated a knock-in mouse line, in which N-terminal hemagglutinin epitope-tagged ␣ 2A -adrenergic receptor (AR) expression was driven by the endogenous mouse ␣ 2A AR gene locus. Exploiting this mouse line, we evaluated ␣ 2A AR trafficking and ␣ 2A AR-mediated inhibition of Ca 2؉ currents in native sympathetic neurons in response to clonidine and guanfacine, two drugs used for treatment of hypertension, attention deficit and hyperactivity disorder, and enhancement of analgesia through actions on the ␣ 2A AR subtype. We discovered a more rapid desensitization of Ca 2؉ current suppression by clonidine than guanfacine, which paralleled a more marked receptor phosphorylation and endocytosis of ␣ 2A AR evoked by clonidine than by guanfacine. Clonidine-induced ␣ 2A AR desensitization, but not receptor phosphorylation, was attenuated by blockade of endocytosis with concanavalin A, indicating a critical role for internalization of ␣ 2A AR in desensitization to this ligand. Our data on endogenous receptor-mediated signaling and trafficking in native cells reveal not only differential regulation of G protein-coupled receptor endocytosis by different ligands, but also a differential contribution of receptor endocytosis to signaling desensitization. Taken together, our data suggest that these HA-␣ 2A AR knock-in mice will serve as an important model in developing ligands to favor endocytosis or nonendocytosis of receptors, depending on the target cell and pathophysiology being addressed.G protein-coupled receptors (GPCRs) 4 represent the largest family of cell surface receptors mediating responses to hormones, cytokines, neurotransmitters, and therapeutic agents (1). In addition to regulating downstream signaling, ligand binding to a receptor can initiate phosphorylation of the active conformation of the receptor by G protein receptor kinases (GRKs) and subsequent binding of arrestins, thus restricting the magnitude and duration of the ligand-evoked signaling responses (2, 3). Binding of arrestins to GPCRs also leads to GPCR internalization (4, 5), a process that has been proposed as a means to desensitize receptor signaling at the cell surface, resensitize receptors, and/or initiate intracellular signaling (6, 7).Different ligands are able to induce distinct signaling and internalization profiles of the same receptor (8 -14). However, the lack of available tools to study trafficking of endogenous GPCRs in native target cells has limited our understanding of ligand-selective endocytosis profiles and the relative contribution of receptor endocytosis to desensitization in native biological settings.To specifically test hypotheses regarding ligand-selective effects on GPCR internalization, and functi...

show abstract

“…Apart from creating a vacuum that may be filled by other drugs with their specific impact on analgesia, avoiding nitrous oxide may also avoid its beneficial analgesic effects [45], some of which may stem from its properties as an NMDA antagonist [46]. A newer drug, dexmedetomidine, an a 2 -agonist administered by continuous intravenous infusion, was recently introduced, is currently approved for sedation during awake craniotomy and is also used for sedation in the setting of the intensive care unit [47]. It may be useful to recognize the perioperative opiate-sparing effects of this class of drug [48].…”

Section: Pain and Intracranial Surgerymentioning

confidence: 99%

The Perioperative Management of Pain from Intracranial Surgery

Gottschalk

Yaster

2008

Neurocrit Care

View full text Add to dashboard Cite

Analgesic therapy following intracranial procedures remains a source of concern and controversy. Although opioids are the mainstay of the "balanced" general anesthetic techniques frequently used during intracranial procedures, neurosurgeons and others have been reluctant to administer opioid analgesics to patients following such procedures. This practice is supported by the concern that the sedation and miosis associated with opioid administration could mask the early signs of intracranial catastrophe, or even exacerbate it through decreased ventilatory drive, elevated arterial carbon dioxide levels, and increased cerebral blood flow. This reluctance to use opioids following intracranial surgery is enabled by decades of training and anecdote emphasizing that pain is minimal following these procedures. However, recent data suggests otherwise, and raises the question of how to provide safe and effective analgesia for these patients. Here, this data is reviewed along with the relevant pain pathways, analgesic drugs and techniques, and the available data on their use following intracranial surgery. Although pain following intracranial surgery appears to be more intense than initially believed, it is readily treated safely and effectively with techniques that have proven useful following other types of surgery, including patient-controlled administration of opioids. The use of multimodal analgesic therapy is emphasized not only for its effectiveness, but to reduce dosages and, therefore, side effects, primarily of the opioids, that could be of legitimate concern to physicians and affect the comfort of their patients.

show abstract

The role of α2-agonists in neurosurgery

Cited by 77 publications

References 67 publications

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

Epitope-tagged Receptor Knock-in Mice Reveal That Differential Desensitization of α2-Adrenergic Responses Is because of Ligand-selective Internalization

The Perioperative Management of Pain from Intracranial Surgery

Contact Info

Product

Resources

About