Cardiovascular and neuronal responses to head stimulation reflect central sensitization and cutaneous allodynia in a rat model of migraine

Current theories propose that migraine pain is caused by chemical activatio n of meningeal perivascular fibers. We previously found that chemical irrit ation of the dura causes trigeminovascular fibers innervating the dura and central trigeminal neurons receiving convergent input from the dura and ski n to respond to low-intensity mechanical and thermal stimuli that previousl y induced minimal or no responses. One conclusion of these studies was that when low- and high-intensity stimuli induce responses of similar magnitude in nociceptive neurons, low-intensity stimuli must be as painful as the hi gh-intensity stimuli. The present study investigates in anesthetized rats t he significance of the changes in the responses of central trigeminal neuro ns (i.e., in nucleus caudalis) by correlating them with the occurrence and type of the simultaneously recorded cardiovascular responses. Before chemic al stimulation of the dura, simultaneous increases in neuronal firing rates and blood pressure were induced by dural indentation with forces greater t han or equal to 2.35 g and by noxious cutaneous stimuli such as pinching th e skin and warming >46 degrees C. After chemical stimulation, similar neuro nal responses and blood pressure increases were evoked by much smaller forc es for dural indentation and by innocuous cutaneous stimuli such as brushin g the skin and warming it to greater than or equal to 43 degrees C. The ons ets of neuronal responses preceded the onsets of depressor responses by 1.7 s and presser responses by 4.0 s. The duration of neuronal responses was 1 5 a, whereas the duration of depressor responses was shorter (5.8 s) and pr esser responses longer (22.7 s) than the neuronal responses. We conclude th at the facilitated cardiovascular and central trigeminal neuronal responses to innocuous stimulation of the skin indicate that when dural stimulation induces central sensitization, innocuous stimuli are as nociceptive as noxi ous stimuli had been before dural stimulation and that a similar process mi ght occur during the development of cutaneous allodynia during migraine.