Medial prefrontal cortex activity is predictive for hyperalgesia and pharmacological antihyperalgesia.
Sodium channel blockers are known for reducing pain and hyperalgesia. In the present study we investigated changes in cerebral processing of secondary mechanical hyperalgesia induced by pharmacological modulation with systemic lidocaine. An experimental electrical pain model was used in combination with functional magnetic resonance imaging. After induction of pin-prick hyperalgesia lidocaine or placebo was administered systemically using a double-blinded design. A 2 x 2 factorial analysis was performed. The factors were (1) sensitization to pain (levels: pin-prick hyperalgesia and normal pin-prick pain) and (2) pharmacological modulation (levels: lidocaine and placebo). A main effect of (1) sensitization was found in bilateral secondary somatosensory cortex (S2), insula, anterior cingulate gyrus (ACC), medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), parietal association cortex (PA), thalamus and contralateral midbrain. A main effect of (2) pharmacological modulation was found in bilateral S2, insula, ACC, mPFC, dlPFC, PA, midbrain and contralateral primary motor cortex, and thalamus. Interaction of pharmacological modulation and sensitization to pin-prick pain with activity increase during hyperalgesia and placebo was found in mPFC, posterior cingulate gyrus and thalamus. However, only activity in mPFC was inversely correlated to area of hyperalgesia during placebo and antihyperalgesic treatment effect. Furthermore, the difference of mPFC activity during hyperalgesia and placebo versus hyperalgesia and lidocaine correlated inversely with the change of the weighted hyperalgesic area (as a factor of area and rated pain intensity). We conclude that activity in mPFC correlates inversely with individual extent of central hyperalgesia and predicts individual pharmacological antihyperalgesic treatment response.
Department of Neurology, University Hospital Erlangen, 91054 Erlangen, Germany.
Frank
F
Seifert
Kathrin
K
Bschorer
Roberto
R
De Col
Jörg
J
Filitz
Elena
E
Peltz
Wolfgang
W
Koppert
Christian
C
Maihöfner
D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D008012:Lidocaine / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D010812:Physical Stimulation; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*
D000779:Anesthetics, Local; D008012:Lidocaine