Projections of neurons in the periaqueductal gray to pontine and medullary catecholamine cell groups involved in the modulation of nociception

Bajic, Dusica; Proudfit, Herbert K.

doi:10.1002/(sici)1096-9861(19990315)405:3<359::aid-cne6>3.0.co;2-w

Cited by 124 publications

(45 citation statements)

References 71 publications

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“…These findings suggest a strong contribution of norepinephrine in antinociception associated with descending inhibition. While neither the PAG nor the RVM contain noradrenergic neurons, both regions communicate with noradrenergic sites important to pain modulation, including the A5 (locus coeruleus), A6, and A7 (Köl-liker-Füse) nuclei (89)(90)(91). These noradrenergic nuclei are a major source of direct noradrenergic projections to the spinal cord (3,92) and likely may serve to ultimately inhibit the response of presynaptic and postsynaptic spinal pain transmission neurons (3,92).…”

Section: Noradrenergic Systems and Pain Modulationmentioning

confidence: 99%

Central modulation of pain

Ossipov¹,

Dussor²,

Porreca³

2010

J. Clin. Invest.

893

728

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It has long been appreciated that the experience of pain is highly variable between individuals. Pain results from activation of sensory receptors specialized to detect actual or impending tissue damage (i.e., nociceptors). However, a direct correlation between activation of nociceptors and the sensory experience of pain is not always apparent. Even in cases in which the severity of injury appears similar, individual pain experiences may vary dramatically. Emotional state, degree of anxiety, attention and distraction, past experiences, memories, and many other factors can either enhance or diminish the pain experience. Here, we review evidence for "top-down" modulatory circuits that profoundly change the sensory experience of pain.

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Section: Noradrenergic Systems and Pain Modulationmentioning

confidence: 99%

Central modulation of pain

Ossipov¹,

Dussor²,

Porreca³

2010

J. Clin. Invest.

893

728

View full text Add to dashboard Cite

show abstract

“…Descending noradrenergic projections to the spinal dorsal horns arise from the A5, the locus coeruleus (A6) and the Kölliker-Füse (A7) pontine noradrenergic nuclei, and these regions communicate with the RVM and PAG [84-87]. Thus, these noradrenergic projections form an important component of descending pain modulation.…”

Section: Descending Pain Modulationmentioning

confidence: 99%

Descending pain modulation and chronification of pain

Ossipov

Morimura

Porreca

2014

Current Opinion in Supportive &Amp; Palliative Care

582

345

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Purpose of review Chronic pain is an important public health problem that negatively impacts quality of life of affected individuals and exacts an enormous socio-economic cost. Currently available therapeutics provide inadequate management of pain in many patients. Acute pain states generally resolve in most patients. However, for reasons that are poorly understood, in some individuals, acute pain can transform to a chronic state. Our understanding of the risk factors that underlie the development of chronic pain is limited. Recent studies have suggested an important contribution of dysfunction in descending pain modulatory circuits to pain ‘chronification’. Human studies provide insights into possible endogenous and exogenous factors that may promote the conversion of pain into a chronic condition. Recent findings Descending pain modulatory systems have been studied and characterized in animal models. Human brain imaging techniques, deep brain stimulation and the mechanisms of action of drugs that are effective in the treatment of pain confirm the clinical relevance of top-down pain modulatory circuits. Growing evidence supports the concept that chronic pain is associated with a dysregulation in descending pain modulation. Disruption of the balance of descending modulatory circuits to favour facilitation may promote and maintain chronic pain. Recent findings suggest that diminished descending inhibition is likely to be an important element in determining whether pain may become chronic. This view is consistent with the clinical success of drugs that enhance spinal noradrenergic activity, such as serotonin/norepinephrine reuptake inhibitors (SNRIs), in the treatment of chronic pain states. Consistent with this concept, a robust descending inhibitory system may be normally engaged to protect against the development of chronic pain. Imaging studies show that higher cortical and subcortical centres that govern emotional, motivational and cognitive processes communicate directly with descending pain modulatory circuits providing a mechanistic basis to explain how exogenous factors can influence the expression of chronic pain in a susceptible individual. Summary Preclinical studies coupled with clinical pharmacologic and neuroimaging investigations have advanced our understanding of brain circuits that modulate pain. Descending pain facilitatory and inhibitory circuits arising ultimately in the brainstem provide mechanisms that can be engaged to promote or protect against pain ‘chronification’. These systems interact with higher centres, thus providing a means through which exogenous factors can influence the risk of pain chronification. A greater understanding of the role of descending pain modulation can lead to novel therapeutic directions aimed at normalizing aberrant processes that can lead to chronic pain.

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“…PAG-mediated antinociception involves the recruitment of pain-modulating RVM neurons via the descending pain pathway (Bajic and Proudfit, 1999). Capsaicin, when injected into the dorsolateral periaqueductal grey (DLPAG), increased the latency of nociceptive responding to noxious heat, indicating that stimulation of TRPV1 within the descending inhibitory pain pathway can cause antinociception (Palazzo et al, 2002).…”

Section: Acute Painmentioning

confidence: 99%