Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans

Abstract

Central sensitization (CS) refers to an increase in the excitability of spinal dorsal horn neurons that results from, and far outlasts the initiating nociceptive input. Here, functional magnetic resonance imaging was used to examine whether supraspinal activity might contribute to the maintenance of CS in humans. A crossover parametric design was used to distinguish and control for brain activity that is related to the consequence of increased pain experienced during CS. When the intensity of pain during CS and normal states were matched, only activity within the brainstem, including the mesencephalic pontine reticular formation, and the anterior thalami remained increased during CS. Further analyses revealed that activity in the isolated brainstem area correlated positively with the force of noxious stimulation only during CS, whereas activity in the isolated thalamic area was not modulated parametrically in either CS or normal states. Additionally, the mean activity in the isolated brainstem area was increased only during CS, whereas the mean activity in the isolated thalamic area was increased in both states, albeit less so in the normal state. Together, these findings suggest a specific role of the brainstem for the maintenance of CS in humans. Regarding brain areas related to the consequence of increased pain perception during CS, we found that only cortical activity, mainly in the primary somatosensory area, was significantly correlated with intensity of pain that was attributable to both the force of noxious stimulation used and state in which noxious stimulation was applied.

Thalamic deep brain stimulation for neuropathic pain after amputation or brachial plexus avulsion

“…32,61 Specific mechanisms of central deafferentation and thalamocortical dysrhythmia that implicate sensory thalamic dysfunction in pain are suggested by nonhuman primate lesional and human functional imaging studies, and consequent thalamic reorganization can be large. 26,28,39,50,54,60 Microelectrode recordings in patients with chronic pain have shown enhanced bursting activity and increased stump representation in amputees.…”

Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations

“…In some conditions, chronic pain is accompanied by hyperalgesia and/or allodynia, which are signs of peripheral and/or central sensitization. This sensitization can be studied by applying brief stimuli, preferably with multiple stimulus intensities to characterize stimulus-response functions 82,83 . With this approach, one can determine the stimulus-evoked brain responses that differ between patients with chronic pain and healthy individuals, or between responses elicited by stimuli applied to affected and unaffected areas of the same patient [83][84][85][86] .…”

“…This sensitization can be studied by applying brief stimuli, preferably with multiple stimulus intensities to characterize stimulus-response functions 82,83 . With this approach, one can determine the stimulus-evoked brain responses that differ between patients with chronic pain and healthy individuals, or between responses elicited by stimuli applied to affected and unaffected areas of the same patient [83][84][85][86] . Alternatively, brain responses that correlate with pain intensity 79,82,[87][88][89][90][91] , or perceptrelated brain activity that fluctuates in synchrony with the experience of pain 31,69,89,[92][93][94][95][96] can be identified.…”

Withdrawal: Proteomic Profiling in the Spinal Cord and Sciatic Nerve in a Global Cerebral Ischemia-Induced Mechanical Allodynia Mouse Model

“…4,5) Cerebral stroke occasionally induces central post-stroke pain (CPSP) that manifests as burning pain, throbbing pain, aching pain, slashing pain, allodynia, and hyperalgesia, either continuously or intermittently on the affected side.…”

“…2,3) Many clinical symptoms can manifest after strokes, including motor deficits, cognitive dysfunction, language problems, emotional disturbances, social maladjustment, somatosensory dysfunction, and central pain. 4,5) Cerebral stroke occasionally induces central post-stroke pain (CPSP) that manifests as burning pain, throbbing pain, aching pain, slashing pain, allodynia, and hyperalgesia, either continuously or intermittently on the affected side. 6,7) CPSP is known to be one of the neuropathic pain.…”