Brain processing of capsaicin-induced secondary hyperalgesia: A functional MRI study

Ralf Baron, Yvonne Baron, Elizabeth Disbrow, Timothy P L Roberts

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)548-557
Number of pages10
Issue number3
StatePublished - Aug 11 1999

ASJC Scopus subject areas

  • Neuroscience(all)


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