Pain Hypersensitivity by Central Neural Plasticity

Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

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Central sensitization represents an enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition and is a manifestation of the remarkable plasticity of the somatosensory nervous system in response to activity, inflammation, and neural injury.

The net effect of central sensitization is to recruit previously subthreshold synaptic inputs to nociceptive neurons, generating an increased or augmented action potential output: a state of facilitation, potentiation, augmentation, or amplification.

Central sensitization is responsible for many of the temporal, spatial, and threshold changes in pain sensibility in acute and chronic clinical pain settings and exemplifies the fundamental contribution of the central nervous system to the generation of pain hypersensitivity.

Because central sensitization results from changes in the properties of neurons in the central nervous system, the pain is no longer coupled, as acute nociceptive pain is, to the presence, intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces pain hypersensitivity by changing the sensory response elicited by normal inputs, including those that usually evoke innocuous sensations.

In many clinical syndromes, pain is no longer protective. The pain in these situations arises spontaneously, can be elicited by normally innocuous stimuli (allodynia), is exaggerated and prolonged in response to noxious stimuli (hyperalgesia), and spreads beyond the site of injury (secondary hyperalgesia).

Central sensitization contributes to neuropathic37 and inflammatory pain,26,274,395 migraine,35 and irritable bowel syndrome.253 In these patients, it is involved in producing abnormal responsiveness to noxious and innocuous stimuli and a spread of tenderness beyond lesion sites. Central sensitization may also play a fundamental role in the abnormal and widespread pain sensitivity in patients with fibromyalgia

Pain is not then simply a reflection of peripheral inputs or pathology but is also a dynamic reflection of central neuronal plasticity. The plasticity profoundly alters sensitivity to an extent that it is a -major contributor to many clinical pain syndromes and represents a major target for therapeutic intervention. The past 26 years have seen enormous advances both in our appreciation of the nature and manifestations of central sensitization and in its underlying molecular mechanisms.

the essence of central sensitization is a constantly changing mosaic of alterations in membrane excitability, reductions in inhibitory transmission, and increases in synaptic efficacy, mediated by many converging and diverging molecular players on a background of phenotypic switches and structural alterations.