What is Central Sensitization?

In the previous post on allodynia and hyperalgesia, I mentioned that sensitization of nociceptive neurons in the dorsal horn of the spinal cord were crucial for the development of allodynia and likely contribute strongly to hyperalgesia. When pain scientist and clinicians talk about this type of sensitization they often refer to it as “central sensitization”. What, exactly does this mean?

Central sensitization is loosely defined as an increased response to stimulation that is mediated by amplification of signaling in the central nervous system (CNS). While the stimulation does not necessarily need to be of noxious intensity, for central sensitization to be present it should recruit mechanisms that would signal a noxious response. An example of this is the case of allodynia. Under normal conditions a non-noxious stimuli may not recruit electrophysiological activity in nociceptive neurons in the dorsal horn. On the other hand, following an injury, this same innocuous stimulation may recruit activity in these same central neurons. This would be an example of central sensitization and, in this case, the sensitization would provide a mechanism for allodynia. Central sensitization was first described by Clifford Woolf. In a Nature paper in 1983 he showed that a thermal injury in the periphery caused an amplification of painful stimuli evoked activity coupled to an augmentation of the flexion reflex response (recorded by EMG). Because this reflex is mediated by a dorsal horn – ventral horn reflex arc this gave evidence that amplification of pain signaling was occurring in the CNS. Importantly, he also noted that the injury (to only one paw) stimulated an increase in the reflex arc on the contralateral side of the body. Because this occurred on the side opposite the injury, it could not have been mediated by peripheral mechanisms and must have involved amplification of signaling in the CNS. He termed this phenomena “central sensitization” and realized that such mechanisms could give rise to pain amplification similar to what is seen in humans following an injury or in chronic pain conditions.

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