α2-Adrenoceptor antagonists enhance responses of dorsal horn neurones to formalin induced inflammation

Green, GM; Lyons, Lila L.; Dickenson, AH

doi:10.1016/s0014-2999(98)00217-9

Cited by 41 publications

(24 citation statements)

References 16 publications

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“…Indeed, it has been suggested that the spinal projection from the LC has analgesic properties [331] and α 2 -adrenoceptor agonists acting in the dorsal horn of the spinal cord are known to produce analgesia [88]. Interestingly, α 2 -adrenoceptor antagonists increase the response of dorsal horn neurones to inflammation induced by formalin injection [121]. Additionally, β-adrenoceptors have been detected in the dorsal horn, and may also be involved with nociception [241].…”

Section: Output Functions Of the Locus Coeruleusmentioning

confidence: 99%

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation

Samuels

Szabadi²

2008

639

510

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The locus coeruleus (LC) is the major noradrenergic nucleus of the brain, giving rise to fibres innervating extensive areas throughout the neuraxis. Recent advances in neuroscience have resulted in the unravelling of the neuronal circuits controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. The LC is a major wakefulness-promoting nucleus, resulting from dense excitatory projections to the majority of the cerebral cortex, cholinergic neurones of the basal forebrain, cortically-projecting neurones of the thalamus, serotoninergic neurones of the dorsal raphe and cholinergic neurones of the pedunculopontine and laterodorsal tegmental nucleus, and substantial inhibitory projections to sleep-promoting GABAergic neurones of the basal forebrain and ventrolateral preoptic area. Activation of the LC thus results in the enhancement of alertness through the innervation of these varied nuclei. The importance of the LC in controlling autonomic function results from both direct projections to the spinal cord and projections to autonomic nuclei including the dorsal motor nucleus of the vagus, the nucleus ambiguus, the rostroventrolateral medulla, the Edinger-Westphal nucleus, the caudal raphe, the salivatory nuclei, the paraventricular nucleus, and the amygdala. LC activation produces an increase in sympathetic activity and a decrease in parasympathetic activity via these projections. Alterations in LC activity therefore result in complex patterns of neuronal activity throughout the brain, observed as changes in measures of arousal and autonomic function.

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Section: Output Functions Of the Locus Coeruleusmentioning

confidence: 99%

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation

Samuels

Szabadi²

2008

639

510

View full text Add to dashboard Cite

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“…(2) ability of such agents to produce analgesia through supraspinal mechanisms [82,83]; (3) the effects of several analgesic agents can be eliminated by selective alpha-2 adrenergic receptor blockade [82][83][84][85][86], and (4) acute pain responses are increased following selective alpha-2 adrenergic blockade [87][88][89]. Limited human data also supports the role of alpha-2 adrenergic mechanisms in endogenous pain modulation.…”

Section: Noradrenergic Mechanismsmentioning

confidence: 99%

“…Central noradrenergic mechanisms also appear to be crucial for descending pain inhibitory pathways [1,[87][88][89]. Although widely studied in the context of acute pain, changes in descending noradrenergic inhibitory pathways associated with chronic pain have been less widely examined.…”

Section: Impaired Descending Inhibitory Mechanismsmentioning

confidence: 99%

Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain

Bruehl

Chung

2004

Neuroscience & Biobehavioral Reviews

326

329

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“…Sustained pain, such as induced by formalin or capsaicin, activates the descending noradrenergic pain inhibitory circuitry reducing pain due to action on spinal á 2 -adrenoceptors. In rats and mice with a sustained nociceptive stimulus, administration of atipamezole blocks the action of descending noradrenergic pain inhibitory pathways and leads to an increase of pain-related responses (9,31,40). In the rabbit, however, an á 2 -adrenoceptor antagonist RX821002, markedly enhanced withdrawal reflexes, although there was no sustained nociceptive stimulation (5).…”

Section: Pain Modulationmentioning

confidence: 99%

Pharmacological Properties, Central Nervous System Effects, and Potential Therapeutic Applications of Atipamezole, a Selective α₂‐Adrenoceptor Antagonist

et al. 2005

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Atipamezole is an alpha2-adrenoceptor antagonist with an imidazole structure. Receptor binding studies indicate that its affinity for alpha2-adrenoceptors and its alpha2/alpha1 selectivity ratio are considerably higher than those of yohimbine, the prototype alpha2-adrenoceptor antagonist. Atipamezole is not selective for subtypes of alpha2-adrenoceptors. Unlike many other alpha2-adrenoceptor antagonists, it has negligible affinity for 5-HT1A and I2 binding sites. Atipamezole is rapidly absorbed and distributed from the periphery to the central nervous system. In humans, atipamezole at doses up to 30 mg/subject produced no cardiovascular or subjective side effects, while at a high dose (100 mg/subject) it produced subjective symptoms, such as motor restlessness, and an increase in blood pressure. Atipamezole rapidly reverses sedation/anesthesia induced by alpha2-adrenoceptor agonists. Due to this property, atipamezole is commonly used by veterinarians to awaken animals from sedation/anesthesia induced by alpha2-adrenoceptor agonists alone or in combination with various anesthetics. Atipamezole increased sexual activity in rats and monkeys. In animals with sustained nociception, atipamezole increased pain-related responses by blocking the noradrenergic feedback inhibition of pain. In tests assessing cognitive functions, atipamezole at low doses has beneficial effects on alertness, selective attention, planning, learning, and recall in experimental animals, but not necessarily on short-term working memory. At higher doses atipamezole impaired performance in tests of cognitive functions, probably due to noradrenergic overactivity. Recent experimental animal studies suggest that atipamezole might have beneficial effects in the recovery from brain damage and might potentiate the anti-Parkinsonian effects of dopaminergic drugs. In phase I studies atipamezole has been well tolerated by human subjects.

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α2-Adrenoceptor antagonists enhance responses of dorsal horn neurones to formalin induced inflammation

Cited by 41 publications

References 16 publications

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation

Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain

Pharmacological Properties, Central Nervous System Effects, and Potential Therapeutic Applications of Atipamezole, a Selective α₂‐Adrenoceptor Antagonist

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α2-Adrenoceptor antagonists enhance responses of dorsal horn neurones to formalin induced inflammation

Cited by 41 publications

References 16 publications

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation

Functional Neuroanatomy of the Noradrenergic Locus Coeruleus: Its Roles in the Regulation of Arousal and Autonomic Function Part I: Principles of Functional Organisation

Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain

Pharmacological Properties, Central Nervous System Effects, and Potential Therapeutic Applications of Atipamezole, a Selective α2‐Adrenoceptor Antagonist

Contact Info

Product

Resources

About

Pharmacological Properties, Central Nervous System Effects, and Potential Therapeutic Applications of Atipamezole, a Selective α₂‐Adrenoceptor Antagonist