The maladaptive brain: excitable pathways to chronic pain

Abstract

As undergraduates, many of us were taught a simple and straightforward description of the anatomy and physiology of pain: the dorsal horn of the spinal cord receives nociceptive input from the periphery, which it transmits up the spinothalamic tract to the thalamus, which in turn gates and relays pain signals to the cerebral cortex where pain is ‘felt’. In this scheme, therefore, chronic pain should result from too much afferent input, or excess sensitivity to normal stimuli. But herein lies a problem: chronic pain rather too often occurs in the absence of any nociceptive input at all. The deeper you look, the more you realize just how much we do not understand about pain. For those who favour the simple feed-forward model, three observations need to be considered. First, there is no ‘pain cortex’: even though regions light up beautifully and reproducibly in response to pain during functional brain imaging experiments, direct stimulation of any single cortical region fails reliably to reproduce the sensation of pain (see Mazzola et al ., 2012: page 640 in this issue). Secondly, information travels the wrong way: a recent study of placebo analgesia showed modulation of activity primarily in the dorsal horn (Eippert et al ., 2009), indicating that beliefs concerning the higher-order modulation of pain may depend as much on the spinal cord as our prefrontal cortex. Lastly, lesions of the classical pain pathway (such as peripheral nerve, spinal cord or thalamus) often result …