Effects of sodium channel blockade on the cerebral processing of mechanical hyperalgesia: a fMRI study

Background: Nerve injury and tissue inflammation can result in spontaneous and evoked pain (hyperalgesia). Basically, primary hyperalgesia is located in the area of injury and is a result of peripheral sensitization, whereas secondary mechanical hyperalgesia develops in the surrounding tissue due to mechanisms of central sensitization. Sodium channel blockade is known for reduction of spontaneous pain and hyperalgesia by predominantly central mechanisms. Therefore, the aim of the present study was to determine changes in cerebral processing of mechanical hyperalgesia induced by pharmacological modulation using lidocaine.

Methods: A surrogate model for neuropathic pain (electrically- induced mechanical hyperalgesia) was used in combination with functional magnetic resonance imaging (fMRI). After induction of pin- prick hyperalgesia lidocaine or placebo was administered systemically. Pin- prick stimuli were applied inside and outside the sensitized areas. A 2×4 factorial analysis was performed. The factors were (i) pharmacological modulation (levels: verum and placebo) and (ii) sensitization to pain (levels: pin- prick hyperalgesia and normal pin- prick pain).

Results: A main effect of (i) pharmacological modulation was found in areas of the pain neuromatrix (anterior cingulate cortex (ACC), prefrontal cortex (PFC), insula, primary somatosensory cortex (S1), secondary somatosensory cortex (S2)). The parietal association cortex (PA) was additionally recruited. A main effect of (ii) sensitization was found in all areas of the pain neuromatrix. Interaction of pharmacological modulation and sensitization to pin- prick pain was found in ACC and medial PFC. Direct comparisons of verum versus placebo conditions were calculated for (i) normal pin- prick pain (analgesia) and (ii) pin- prick hyperalgesia (antihyperalgesia). Lidocaine effects were found (i) for analgesia in the bilateral anterior insula and S2, and (ii) for antihyperalgesia in pain related areas ACC, PFC, insula, S1 and S2.

Conclusion: Using a 2×4 factorial analysis in this fMRI study, antihyperalgesic effects of sodium channel blockade could be detected in ACC and medial PFC.

Supported by the „German Research Network for Neuropathic Pain“ (Deutscher Forschungsverbund Neuropathischer Schmerz, BMBF).