J Clin Neurol.  2012 Jun;8(2):89-99.

Sensitization of the Trigeminovascular Pathway: Perspective and Implications to Migraine Pathophysiology

• Bernstein
• Burstein R

Abstract

Migraine headache is commonly associated with signs of exaggerated intracranial and extracranial mechanical sensitivities. Patients exhibiting signs of intracranial hypersensitivity testify that their headache throbs and that mundane physical activities that increase intracranial pressure (such as bending over or coughing) intensify the pain. Patients exhibiting signs of extracranial hypersensitivity testify that during migraine their facial skin hurts in response to otherwise innocuous activities such as combing, shaving, letting water run over their face in the shower, or wearing glasses or earrings (termed here cephalic cutaneous allodynia). Such patients often testify that during migraine their bodily skin is hypersensitive and that wearing tight cloth, bracelets, rings, necklaces and socks or using a heavy blanket can be uncomfortable and/or painful (termed her extracephalic cutaneous allodynia). This review summarizes the evidence that support the view that activation of the trigeminovascular pathway contribute to the headache phase of a migraine attack, that the development of throbbing in the initial phase of migraine is mediated by sensitization of peripheral trigeminovascular neurons that innervate the meninges, that the development of cephalic allodynia is propelled by sensitization of second-order trigeminovascular neurons in the spinal trigeminal nucleus which receive converging sensory input from the meninges as well as from the scalp and facial skin, and that the development of extracephalic allodynia is mediated by sensitization of third-order trigeminovascular neurons in the posterior thalamic nuclei which receive converging sensory input from the meninges, facial and body skin.

Keyword

headache; trigeminal; pain; triptans; noiciceptrion; thalamus

MeSH Terms

Ear
Eyeglasses
Glass
Headache
Humans
Hyperalgesia
Hypersensitivity
Intracranial Pressure
Linear Energy Transfer
Meninges
Migraine Disorders
Motor Activity
Neurons
Posterior Thalamic Nuclei
Scalp
Skin
Thalamus
Trigeminal Nucleus, Spinal
Tryptamines
Water
Tryptamines
Water

Figure

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  Fig. 1 Sensitization of peripheral trigeminovascular neuron (meningeal nociceptor) believed to mediate intracranial hypersensitivity. A: Experimental setup. B: Development of mechanical hypersensitivity over time. IS: inflammatory soup.

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  Fig. 2 Sensitization of central trigeminovascular neuron in the spinal trigeminal nucleus believed to mediate extracranial hypersensitivity and cephalic allodynia. A: Experimental setup. B: Recording site. C: Development of mechanical sensitization. D: Expansion of cephalic cutaneous receptive field. IS: inflammatory soup.

• 

  Fig. 3 Clinical presentation of cephalic and extracephalic allodynia during migraine. Number depict pain intensity, cold pain threshold, heat pain threshold and mechanical pain threshold. Areas shaded in green indicate values considered as allodynic. CL: contralateral, IL: ipsilateral, VFH: von-fray hair.

• 

  Fig. 4 Sensitization of central trigeminovascular neuron in the posterior thalamic nucleus believed to mediate extracranial allodynia. A: Expansion of cutaneous receptive field. B: Development of spontaneous activity. C: Enhanced responses to mechanical (top) and thermal (bottom) stimuli. Br: brush, H: habenula, IC: internal capsule, IS: inflammatory soup, Pi: pinch, PO: posterior thalamic nucleus, Pr: pressure, VPM: ventral posteromedial thalamic nucleus, VPL: ventral posterolateral thalamic nucleus.

• 

  Fig. 5 Contrast analysis of blood oxygenation level-dependent signals registered in fMRI scans of the human posterior thalamus following innocuous and noxious skin stimuli during migraine attacks that were associated with extracephalic allodynia. ac: anterior commissure, cc: corpus callosum, CL: centrolateral thalamic nucleus, CM: centromedian thalamic nucleus, MD: mediodorsal thalamic group, Li: limitans thalamic nucleus, pc: posterior commissure, PF: parafascicular thalamic nucleus, Pul: pulvinar, VPL: ventral posterolateral thalamic.

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