Mapping the spinal and supraspinal pathways of dynamic mechanical allodynia in the human trigeminal system using cardiac-gated fMRI

Abstract

Following injury and inflammation, pain to light stroking (dynamic mechanical allodynia) might develop at the damaged site (primary area) or in adjacent normal tissue (secondary area).Using fMRI we mapped changes in the spinal trigeminal nucleus (spV), and supraspinal brainstem nuclei following heat/capsaicin-induced primary and secondary dynamic mechanical allodynia in the human trigeminal system. The role of these structures in dynamic mechanical allodynia has not been clarified yet in humans. During the control session we applied the same mechanical stimuli to the same untreated trigeminal area.Primary and secondary mechanical allodynia showed equal levels of perceived pain intensity, and compared to control mechanical stimulation exhibited similar responses in the ipsilateral spV and contralateral ventrolateral periaqueductal gray (vlPAG). Activity in the spV was significantly higher during both conditions versus the control mechanical stimulation, indicating that central sensitization of second-order neurons is similar for primary and secondary mechanical allodynia. The vlPAG showed decreased activity that inversely correlated with pain ratings during primary allodynia, i.e. the more deactivated the vlPAG the higher the pain intensity (p<0.05, Pearson's correlation).Primary and secondary dynamic mechanical allodynia were also characterized by significant differences involving distinct supraspinal structures mainly involved in pain modulation and including the rostroventromedial medulla, pons reticular formation, dorsolateral PAG, all more active during primary versus secondary allodynia, and the medial reticular formation of the caudal medulla that was more active during secondary versus primary allodynia. These results indicate the pain modulatory system is involved to a different extent during primary versus secondary mechanical allodynia.

Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans

“…Furthermore, SI activity was significantly correlated with the intensity of pain that was experienced on a trial-by-trial basis in the normal state as well as during CS. These findings suggest that the increased cortical activity found in SI and ACC in previous neuroimaging studies of secondary mechanical hyperalgesia (Iadarola et al, 1998;Baron et al, 1999;Zambreanu et al, 2005;Mainero et al, 2007) mainly reflects the increased intensity of pain experienced during CS.…”

“…Nearly a decade of neuroimaging research has revealed that supraspinal activity is increased during mechanical hyperalgesia that is experimentally induced by capsaicin in healthy volunteers (Iadarola et al, 1998;Baron et al, 1999;Zambreanu et al, 2005;Mainero et al, 2007). Increased activity is found in the brainstem, the thalami, cerebellum, primary and secondary somatosensory cortices, insula and cingulate cortex.…”

Differential activation of the human trigeminal nuclear complex by noxious and non‐noxious orofacial stimulation

“…To the best of our knowledge only two studies have used brain imaging techniques to define orofacial pain processing and these investigations report signal increases within SpVc during noxious cutaneous stimulation [DaSilva et al, 2002;Mainero et al, 2007]. To date, no study has examined brain activation patterns during orofacial pain which originates in deeper structures such as muscle.…”

Bilateral brainstem activation by thermal stimulation of the face in healthy volunteers

“…After specification of the experimental design and computation of b-errors, activation projected onto the individual anatomies was displayed. Minimal cluster size was set to 3 voxel (10.7 mm 3 ) [11,36] with uncorrected P \ 0.02 (T [ 2.06) for activation in the pons and P \ 0.05 (T [ 1.65) in the medulla/spinal dorsal horn (SDH). Images were overlaid by anatomically corresponding drawings derived from two different brainstem atlases [12,15].…”