Tbe development of cutaneous allodynia during a migraine attack - Clinicalevidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine

Recently, we showed that most migraine patients exhibit cutaneous allodynia inside and outside their pain-referred areas when examined during a fully developed migraine attack. In this report, we studied the way in which cuta neous allodynia develops by measuring the pain thresholds in the head and f orearms bilaterally at several time points during a migraine attack in a 42 -year-old male. Prior to the headache, he experienced visual, sensory, moto r and speech aura. During the headache, he experienced photo-, phono- and o dour-phobia, nausea and vomiting, worsening of the headache by coughing or moving his head, and cutaneous pain when shaving, combing his hair or touch ing his scalp. Comparisons between his pain thresholds in the absence of mi graine and at 1, 2 and 4 h after the onset of migraine revealed the followi ng. (i) After 1 h, mechanical and cold allodynia started to develop in the ipsilateral head but not in any other site. (ii) After 2 h, this allodynia increased on the ipsilateral head and spread to the contralateral head and ipsilateral forearm, (iii) After 4 h, heat allodynia was also detected whil e mechanical and cold allodynia continued to increase. These clinical obser vations suggest the following sequence of events along the trigeminovascula r pain pathway of this patient. (i) A few minutes after the initial activat ion of his peripheral nociceptors, they became sensitized; this sensitizati on can mediate the symptoms of intracranial hypersensitivity. (ii) The barr age of impulses that came from the peripheral nociceptors activated second- order neurons and initiated their sensitization; this sensitization can med iate the development of cutaneous allodynia on the ipsilateral head. (iii) The barrage of impulses that came from the sensitized second-order neurons activated and eventually sensitized third-order neurons; this sensitization can mediate the development of cutaneous allodynia on the contralateral he ad and ipsilateral forearm at the 2-h point, over 1 h after the appearance of allodynia on the ipsilateral head. This interpretation calls for an earl y use of anti-migraine drugs that target peripheral nociceptors, before the development of central sensitization. If central sensitization develops, t he therapeutic rationale is to suppress it. Because currently available dru gs that aim to suppress central sensitization are ineffective, this study s tresses the need to develop them for the treatment of migraine.