Brain activity associated with pain and hyperalgesia: an ale meta-analysis

Background: The use of functional brain imaging techniques offers the possibility to uncover the cerebral processing of the human pain experience. Many imaging studies have focused on defining a network of brain structures involved in the processing of normal pain. In addition it was shown that stimulus-evoked pain, which is a frequent symptom of neuropathic pain, causes distinct patterns of brain activation. In the present study we analyzed the data of the previous studies quantitatively.

Methods: Studies were collected by a MEDLINE query. A meta-analysis using the activation-likelihood-estimation (ALE) method to quantify the found results was conducted. We used this data to summarize and compare the cerebral activations of (i) normal and stimulus-evoked pain, (ii) thermal and mechanical pain, (iii) different types of stimulus evoked pain (hyperalgesia, allodynia), and (iv) clinical and experimental pain.

Results: Thirty-three studies, among them fMRI was used in 23 and PET was used in 10 studies, are reviewed in this meta-analysis. When (i) brain processing of normal pain was compared to stimulus evoked pain, allodynia and hyperalgesia induced stronger activation of bilateral S2 compared to normal pain. Inversely, stronger activation of the thalamus, the ACC and the VLPFC was found during normal pain stimuli. When (ii) the effect of stimulus modality was tested, normal thermal stimuli led to stronger activation of the bilateral ACC, bilateral anterior insula, bilateral thalamus, bilateral S2 and the contralateral VLPFC. In allodyia/hyperalgesia, significant more activation was found during thermal stimuli in bilateral ACC, insular regions and PA. In contrast mechanically and electrically allodynia/hyperalgesia induced an increased bilateral activation of the DLPFC, the posterior insula and of ipsilateral S1 and S2. Also, significant (iii) differences between allodynia and hyperalgesia were found. While allodynia produced a stronger bilateral activation of the VLPFC and S2, hyperalgesia led to a more intense activation of the bilateral ACC, DLPFC and the ipsilateral medial prefrontal cortex (MPFC). Finally, we tested for (iv) a difference between experimental and clinical pain In healthy subjects hyperalgesia/allodynia led to a stronger activation in nearly all pain relevant areas (ACC, insula, DLPFC, MPFC, S1, S2).

Conclusion: The results suggest the existence of distinct, although overlapping, neuronal networks related to these different types of pain.