Thalamic sensitization transforms localized pain into widespread allodynia

Abstract

Objective-Focal somatic pain can evolve into widespread hypersensitivity to non-painful 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 BOLD signals registered in 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 (e.g., brush) became as effective as noxious stimuli (e.g., pinch) in eliciting large bouts of neuronal firing after sensitization was established. In migraine patients, functional MRI assessment of blood oxygenation level-dependent (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.Interpretation-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.

Altered processing of sensory stimuli in patients with migraine

“…147 In another fMRI study, thalamic sensitization cor related with widespread mechanical allodynia during the migraine attack. 148 Moreover, in a diffusion tensor MRI study, our research group found dynamic ictal and inter ictal microstructural variations in the thalamus that were related to the time since the last migraine attack, and seemed to mimic the cyclic neurophysiological changes described above. 149 Collectively, these observations suggest that a search for optimal methods of influencing the cortical tem poral processing of exogenous stimuli that can trigger a migraine attack, or methods for modulating endo genous trigeminal noxious inputs that lead to central sensitization and eventually chronic headache, could result in novel interventions for migraine prevention.…”

Sensitization and pain

“…These functional characteristics appeared after mechanical or thermal stimulation of extracephalic skin areas [34,7]. The same group, through fMRI studies during migraine attack in patients with whole-body allodynia, described a specific thalamic activation after brush and heat stimuli [38].…”

Pain Threshold in Migraine and Tension-Type Headache by Pressure Algometry in Craniocervical Muscles and Peripheral Nerves in Both Genders

“…Development of pulsatility in the initial phase of migraine is mediated by sensitization of peripheral neurons of the trigeminal vascular system and allodynia cutaneous later during acute migraine is propelled by sensitization central neurons [32]. We have found the lowest pain thresholds in patients with longer duration of headache (over 10 years), probably by constant inflammatory state that sensitizes cranial nociceptors, leading to decreased activation of its receptors.…”