Thalamic sensitization transforms localized pain into widespread allodynia.
OBJECTIVE
Focal somatic pain can evolve into widespread hypersensitivity to nonpainful and painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that transformation of headache into whole-body allodynia/hyperalgesia during a migraine attack is mediated by sensitization of thalamic neurons that process converging sensory impulses from the cranial meninges and extracephalic skin.


METHODS
Extracephalic allodynia was assessed using single unit recording of thalamic trigeminovascular neurons in rats and contrast analysis of blood oxygenation level-dependent (BOLD) signals registered in functional magnetic resonance imaging (fMRI) scans of patients exhibiting extracephalic allodynia.


RESULTS
Sensory neurons in the rat posterior thalamus that were activated and sensitized by chemical stimulation of the cranial dura exhibited long-lasting hyperexcitability to innocuous (brush, pressure) and noxious (pinch, heat) stimulation of the paws. Innocuous, extracephalic skin stimuli that did not produce neuronal firing at baseline (eg, brush) became as effective as noxious stimuli (eg, pinch) in eliciting large bouts of neuronal firing after sensitization was established. In migraine patients, fMRI assessment of BOLD signals showed that brush and heat stimulation at the skin of the dorsum of the hand produced larger BOLD responses in the posterior thalamus of subjects undergoing a migraine attack with extracephalic allodynia than the corresponding responses registered when the same patients were free of migraine and allodynia.


CONCLUSIONS
We propose that the spreading of multimodal allodynia and hyperalgesia beyond the locus of migraine headache is mediated by sensitized thalamic neurons that process nociceptive information from the cranial meninges together with sensory information from the skin of the scalp, face, body, and limbs.
Burstein
Rami
R
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Boston, MA. rburstei@bidmc.harvard.edu
Jakubowski
Moshe
M
Garcia-Nicas
Esther
E
Kainz
Vanessa
V
Bajwa
Zahid
Z
Hargreaves
Richard
R
Becerra
Lino
L
Borsook
David
D
D000200:Action Potentials; D000293:Adolescent; D000328:Adult; D000818:Animals; D002560:Cerebrovascular Circulation; D004388:Dura Mater / Q000503:physiopathology; D006358:Hot Temperature; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D008881:Migraine Disorders / Q000503:physiopathology*; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology; D013788:Thalamus / Q000098:blood supply / Q000503:physiopathology*; D055815:Young Adult
D010100:Oxygen