The development of cutaneous allodynia during a migraine attack Clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine

Abstract

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 cutaneous allodynia develops by measuring the pain thresholds in the head and forearms bilaterally at several time points during a migraine attack in a 42-year-old male. Prior to the headache, he experienced visual, sensory, motor and speech aura. During the headache, he experienced photo-, phono- and odour-phobia, nausea and vomiting, worsening of the headache by coughing or moving his head, and cutaneous pain when shaving, combing his hair or touching his scalp. Comparisons between his pain thresholds in the absence of migraine and at 1, 2 and 4 h after the onset of migraine revealed the following. (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 while mechanical and cold allodynia continued to increase. These clinical observations suggest the following sequence of events along the trigeminovascular pain pathway of this patient. (i) A few minutes after the initial activation of his peripheral nociceptors, they became sensitized; this sensitization can mediate the symptoms of intracranial hypersensitivity. (ii) The barrage of impulses that came from the peripheral nociceptors activated second-order neurons and initiated their sensitization; this sensitization can mediate 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 head 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 early use of anti-migraine drugs that target peripheral nociceptors, before the development of central sensitization. If central sensitization develops, the therapeutic rationale is to suppress it. Because currently available drugs that aim to suppress central sensitization are ineffective, this study stresses the need to develop them for the treatment of migraine.

Indomethacin, alone and combined with prochlorperazine and caffeine, but not sumatriptan, abolishes peripheral and central sensitization in in vivo models of migraine

“…Then the barrage of impulses that come from the hyperactive secondorder neurons sensitizes third-order thalamic neurons, mediating the development of CA on the contralateral head and ipsilateral forearm over 1 hour after the appearance of allodynia on the ipsilateral head. 6 Moreover, the efficacy of triptan therapy in patients with or without CA, defined by differences between migraine and baseline pain thresholds to mechanical and thermal stimulation of periorbital skin, has been investigated. 5 Triptan treatment of migraine was equally ineffective once CA was present and equally effective in the absence of CA.…”

Altered processing of sensory stimuli in patients with migraine

“…This amplification also occurs during migraine attacks 108 and worsens with increasing attack frequency. 109 One mechanism underlying central sensi tization is the activity dependent change in excitability of central nociceptors, which results in abnormal ampli fication of pain sensation in physiological nociceptiona phenomenon referred to as temporal summation of pain stimuli 110 that is equivalent to 'wind up' phenomenon (facilitation of wide dynamic range nociceptive neurons located in the deep laminae of the spinal cord dorsal horn and the spinal trigeminal nucleus after constant intensity stimulation of C fibres) in animal experiments.…”

Migraine and motion sickness: What is the link?

“…Cutaneous allodynia and hyperalgesia develops in the distal extremities during the later stages of migraine headache (Burstein, Cutrer, and Yarnitsky, 2000;Burstein, Collins and Jakubowski, 2004;Levy, Jakubowski and Burstein, 2004;Yarnitsky, Goor-Aryeh, Bajwa, Ransil, Cutre, Sottile and Burstein, 2003). The progression of hyperalgesia from the site of headache to more distal regions implies that sensitization spreads rostally in nociceptive networks as the attack progresses (Burstein et al, 2000).…”