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Deepening understanding of the neural substrates of chronic pain

Michael W. Salter
DOI: http://dx.doi.org/10.1093/brain/awu028 651-653 First published online: 18 February 2014

Chronic pain has been labelled the silent health crisis, afflicting hundreds of millions of people worldwide. Chronic pain causes more disability than cancer and heart disease, and the annual monetary cost of treatment and lost productivity is above $500 billion per annum in the United States alone (Institute of Medicine, 2011). Once considered simply a response to disease or injury, chronic pain is increasingly recognized as a group of mechanistically separable nervous system processes produced and maintained by a variety of abnormal cellular signalling pathways (Woolf and Salter, 2000).

A growing number of signalling pathways in the peripheral and central nervous systems have been implicated in chronic pain, along with neuron–glia as well as neuron–neuron interactions (Beggs et al., 2012b), and genetic sensitivity (Mogil, 2012) coupled with epigenetic modulation (Stone and Szyf, 2013). Nevertheless, a core unresolved question is which neurons in the pain processing and transmission circuitry in the spinal cord provide the pathological output believed by most to drive the brain’s pain network in chronic pain. And how is the firing activity of those spinal cord neurons altered? In the current issue of Brain, Yves De Koninck and colleagues take a major step forward in answering these questions through their elegant investigation of de novo changes in neurons in the spinal dorsal horn after peripheral nerve injury (Lavertu et al., 2014). The authors leveraged work from a number of groups that had indicated that loss of Cl-mediated inhibition, particularly in neurons in the superficial laminae of the dorsal horn of the spinal cord (Moore et al., 2002; Coull et al., 2003), is critical for chronic pain hypersensitivity. In particular, De Koninck’s group had previously discovered that disinhibition …

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