Temporal summation of trigeminal pain in human anterior cingulate cortex

Temporal summation of nociceptive inputs in trigeminal networks can induce central sensitization and maintain chronic pain. We combined functional magnetic resonance imaging and electrically evoked pain-related potentials (PREP) in healthy human subjects to identify brain regions involved in temporal summation of nociceptive inputs. We stimulated the skin innervated by the ophthalmic division of the trigeminal nerve with trains of three, seven and eleven similar nociceptive pulses, while recording evoked hemodynamic or electrical brain responses. We found that PREP amplitudes and pain ratings increased in parallel with increasing train length. Strikingly, only hemodynamic responses in the posterior part of the anterior cingulate cortex (pACC) scaled with individual pain ratings on a verbal rating scale (VRS) and electrically evoked responses (i.e., PREP amplitudes for the three train lengths). These findings indicate that pACC codes temporal summation of trigeminal nociception and in this regard may be important for the development of central sensitization observed in chronic head and facial pain.