TY - JOUR
T1 - The development of cutaneous allodynia during a migraine attack. Clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine
AU - Burstein, Rami
AU - Cutrer, Michael F.
AU - Yarnitsky, David
N1 - Funding Information:
We wish to thank Drs Howard Fields, Clifford Saper, Clifford Woolf, Michael Moskowitz and Bernard Ransil for valuable discussions during the preparation of the manuscript. The research was supported by NIH grants DE-10904 (National Institutes of Dental and Craniofacial Research) and NS-35611-01 (National Institutes of Neurological Disorder and Stroke) to R.B., by the Education Fund of the Department of Anesthesia and Critical Care at Beth Israel Deaconess Medical Center, by the Goldfarb and Fink families and the Boston Foundation. Data organization and analysis were carried out on the Prophet System (Release 4.1), a national computing resource for life science research sponsored by the NIH, Division of Research Resources.
PY - 2000/8
Y1 - 2000/8
N2 - 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.
AB - 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.
KW - Allodynia
KW - Headache
KW - Migraine
KW - Pain
KW - Sensitization
UR - http://www.scopus.com/inward/record.url?scp=0033925222&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033925222&partnerID=8YFLogxK
U2 - 10.1093/brain/123.8.1703
DO - 10.1093/brain/123.8.1703
M3 - Article
C2 - 10908199
AN - SCOPUS:0033925222
SN - 0006-8950
VL - 123
SP - 1703
EP - 1709
JO - Brain
JF - Brain
IS - 8
ER -