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Brain processing of capsaicin-induced secondary hyperalgesia: a functional MRI study
1Department of Neurology, University of California at San Francisco, USA. r.baron@neurologie.uni-kiel.de
Objective:
To investigate, using functional MRI (fMRI), the neural network that is activated by the pain component of capsaicin-induced secondary mechanical hyperalgesia.
Background:
Mechanical hyperalgesia (i.e., pain to innocuous tactile stimuli) is a distressing symptom of neuropathic pain syndromes. Animal experiments suggest that alterations in central pain processing occur that render tactile stimuli capable of activating central pain-signaling neurons. A similar central sensitization can be produced experimentally with capsaicin.
Methods:
In nine healthy individuals the cerebral activation pattern resulting from cutaneous nonpainful mechanical stimulation at the dominant forearm was imaged using fMRI. Capsaicin was injected adjacent to the stimulation site to induce secondary mechanical hyperalgesia. The identical mechanical stimulation was then perceived as painful without changing the stimulus intensity and location. Both activation patterns were compared to isolate the specific pain-related component of mechanical hyperalgesia from the tactile component.
Results:
The pattern during nonpainful mechanical stimulation included contralateral primary sensory cortex (SI) and bilateral secondary sensory cortex (SII) activity. During hyperalgesia, significantly higher activation was found in the contralateral prefrontal cortex: the middle (Brodmann areas [BAs] 6, 8, and 9) and inferior frontal gyrus (BAs 44 and 45). No change was present within SI, SII, and the anterior cingulate cortex.
Conclusions:
Prefrontal activation is interpreted as a consequence of attention, cognitive evaluation, and planning of motor behavior in response to pain. The lack of activation of the anterior cingulate contrasts with physiologic pain after C-nociceptor stimulation. It might indicate differences in the processing of hyperalgesia and C-nociceptor pain or it might be due to habituation of affective sensations during hyperalgesia compared with acute capsaicin pain.
Insights
Functional MRI (fMRI) revealed that the pain of capsaicin-induced mechanical hyperalgesia activates the prefrontal cortex, not the sensory cortex. This suggests pain processing involves cognitive evaluation rather than solely sensory pathways.
Area of Science:
- Neuroscience
- Pain Research
- Neuroimaging
Background:
- Mechanical hyperalgesia, pain from non-painful touch, is a common neuropathic pain symptom.
- Central sensitization, altered pain processing in the brain, is implicated in hyperalgesia.
- Capsaicin can experimentally induce central sensitization and secondary mechanical hyperalgesia.
Purpose of the Study:
- To investigate the neural network activated by the pain component of capsaicin-induced secondary mechanical hyperalgesia using functional MRI (fMRI).
- To differentiate the neural activity associated with the painful sensation of hyperalgesia from the tactile sensation itself.
Main Methods:
- Functional MRI (fMRI) was used to image brain activity in nine healthy individuals.
- Mechanical stimulation was applied to the forearm, first when non-painful and then during capsaicin-induced secondary hyperalgesia.
- Brain activation patterns were compared to isolate the pain-specific component of mechanical hyperalgesia.
Main Results:
- Non-painful stimulation activated the contralateral primary sensory cortex (SI) and bilateral secondary sensory cortex (SII).
- During hyperalgesia, significantly increased activation was observed in the contralateral prefrontal cortex (middle and inferior frontal gyrus).
- No significant changes in activation were found in SI, SII, or the anterior cingulate cortex during hyperalgesia.
Conclusions:
- Prefrontal cortex activation during hyperalgesia is linked to attention, cognitive evaluation, and motor planning in response to pain.
- The absence of anterior cingulate cortex activation contrasts with findings in C-nociceptor pain, suggesting distinct processing pathways.
- This may indicate differences in how hyperalgesia and acute C-nociceptor pain are processed, or habituation of affective responses.
