Central modulation of pain
Michael H. Ossipov, … , Gregory O. Dussor, Frank Porreca
Michael H. Ossipov, … , Gregory O. Dussor, Frank Porreca
Published November 1, 2010
Citation Information: J Clin Invest. 2010;120(11):3779-3787. https://doi.org/10.1172/JCI43766.
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Central modulation of pain

Abstract

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.

Authors

Michael H. Ossipov, Gregory O. Dussor, Frank Porreca

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Figure 1

Schematic representation of pain modularity circuitry.

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Schematic representation of pain modularity circuitry. Nociceptive input...
Nociceptive inputs enter the spinal dorsal horn through primary afferent fibers that synapse onto transmission neurons. The projection fibers ascend through the contralateral spinothalamic tract. Ascending projections target the thalamus, and collateral projections also target mesencephalic nuclei, including the DRt, the RVM, and the midbrain PAG. Descending projections from the DRt are a critical component of the DNIC pathway. Rostral projections from the thalamus target areas that include cortical sites and the amygdala. The lateral capsular part of the CeA (“nociceptive amygdala”) receives nociceptive inputs from the brainstem and spinal cord. Inputs from the thalamus and cortex enter through the lateral (LA) and basolateral (BLA) amygdala. The CeA sends outputs to cortical sites and the thalamus, in which cognitive and conscious perceptions of pain are integrated. Descending pain modulation is mediated through projections to the PAG, which also receives inputs from other sites, including the hypothalamus (data not shown), and communicates with the RVM as well as other medullary nuclei that send descending projections to the spinal dorsal horn through the DLF. The noradrenergic locus coeruleus (LC) receives inputs from the PAG, communicates with the RVM, and sends descending noradrenergic inhibitory projections to the spinal cord. Antinociceptive and pronociceptive spinopetal projections from the RVM positively and negatively modulate nociceptive inputs and provide for an endogenous pain regulatory system. Ascending (red) and descending (green) tracts are shown schematically. Areas labeled “i–iv” in the small diagram correspond with labeled details of the larger diagram.