Chronic Pain: Lost Inhibition?

Abstract

Human brain imaging has revealed that acute pain results from activation of a network of brain regions, including the somatosensory, insular, prefrontal, and cingulate cortices. In contrast, many investigations report little or no alteration in brain activity associated with chronic pain, particularly neuropathic pain. It has been hypothesized that neuropathic pain results from misinterpretation of thalamocortical activity, and recent evidence has revealed altered thalamocortical rhythm in individuals with neuropathic pain. Indeed, it was suggested nearly four decades ago that neuropathic pain may be maintained by a discrete central generator, possibly within the thalamus. In this investigation, we used multiple brain imaging techniques to explore central changes in subjects with neuropathic pain of the trigeminal nerve resulting in most cases (20 of 23) from a surgical event. Individuals with chronic neuropathic pain displayed significant somatosensory thalamus volume loss (voxel-based morphometry) which was associated with decreased thalamic reticular nucleus and primary somatosensory cortex activity (quantitative arterial spin labeling). Furthermore, thalamic inhibitory neurotransmitter content was significantly reduced (magnetic resonance spectroscopy), which was significantly correlated to the degree of functional connectivity between the somatosensory thalamus and cortical regions including the primary and secondary somatosensory cortices, anterior insula, and cerebellar cortex. These data suggest that chronic neuropathic pain is associated with altered thalamic anatomy and activity, which may result in disturbed thalamocortical circuits. This disturbed thalamocortical activity may result in the constant perception of pain.

In vivo detection of acute pain-induced changes of GABA+ and Glx in the human brain by using functional 1H MEGA-PRESS MR spectroscopy

“…Recent proton MRS studies identified permanently decreased GABA concentrations and altered Glu or Glx levels compared to healthy controls indicating impairments in neurotransmission (Harris and Clauw, 2012;Henderson et al, 2013). However, since these measurements were performed under resting state conditions only, they are unable to differentiate between changes solely reflecting disordered neuronal regulations or being also related to degenerative cellular changes.…”

Frontostriatal Gating of Tinnitus and Chronic Pain

“…In chronic pain, studies with PET [58-61] and arterial spin labeling MRI [62-65] show increases of blood flow and metabolism in prefrontal, cingulate, and insular cortices and in the striatum as well as decreases in the thalamus. Some of these blood flow changes positively relate to pain intensity (e.g.…”

Enhanced serotonin and mesolimbic dopamine transmissions in a rat model of neuropathic pain

“…Molecular and functional studies on humans and animal models have shown that several brain areas, such as the periaqueductal grey (Baliki et al, 2014;Palazzo et al, 2012), the anterior cingulate cortex (Barthas et al, 2015;Rainville et al, 1997), the prefrontal cortex (Metz et al, 2009;Zhang et al, 2004) and the thalamus (Baliki et al, 2014;Henderson et al, 2013) are involved in pain processing.…”