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The Journal of Neuroscience, October 18, 2006, 26(42):10646-10657; doi:10.1523/JNEUROSCI.2305-06.2006

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Neurobiology of Disease
Trigeminal Neuropathic Pain Alters Responses in CNS Circuits to Mechanical (Brush) and Thermal (Cold and Heat) Stimuli

Lino Becerra,1 Susie Morris,1 Shelly Bazes,1 Richard Gostic,1 Seth Sherman,1 Julie Gostic,1 Gautam Pendse,1 Eric Moulton,1 Steven Scrivani,2 David Keith,3 Boris Chizh,4 and David Borsook1

1Pain and Analgesia Imaging and Neuroscience Group, Department of Psychiatry, McLean Hospital, Belmont, Massachusetts 02478, and Harvard Medical School, Boston, Massachusetts 02115, 2The Craniofacial Pain Center, Tufts University School of Dental Medicine, Boston, Massachusetts 02111, 3Oral and Maxillofacial Surgery Department, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, and 4Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Cambridge CB2 2GG, United Kingdom

Correspondence should be addressed to Dr. David Borsook, Brain Imaging Center, McLean Hospital, Harvard Medical School, Boston, MA 02115. Email: dborsook{at}mclean.harvard.edu

Functional magnetic resonance imaging was used to study patients with chronic neuropathic pain involving the maxillary region (V2) of the trigeminal nerve in patients with spontaneous pain and evoked pain to brush (allodynia). Patients underwent two functional scans (2–3 months apart) with mechanical and thermal stimuli applied to the affected region of V2 and to the mirror site in the unaffected contralateral V2 region, as well as bilaterally to the mandibular (V3) division. Patients were stimulated with brush, noxious cold, and noxious heat. Significant changes were observed in regions within and outside the primary trigeminal sensory pathway. Stimulation to the affected (neuropathic) side resulted in predominantly frontal region and basal ganglia activation compared with the control side. The differences were consistent with the allodynia to brush and cold. A region of interest-based analysis of the trigeminal sensory pathway revealed patterns of activation that differentiated between the affected and unaffected sides and that were particular to each stimulus. Activation in the spinal trigeminal nucleus was constant in location for all pain stimuli. Activation in other brainstem nuclei also showed differences in the blood oxygenation level-dependent signal for the affected versus the unaffected side. Thus, sensory processing in patients with trigeminal neuropathic pain is associated with distinct activation patterns consistent with sensitization within and outside of the primary sensory pathway.

Key words: brainstem; caudate; dorsal horn; facial; neuropathology; noxious; pain; peripheral nerve; phenotype; prefrontal cortex; somatosensory cortex; trigeminal


Received May 31, 2006; revised July 25, 2006; accepted Aug. 15, 2006.

Correspondence should be addressed to Dr. David Borsook, Brain Imaging Center, McLean Hospital, Harvard Medical School, Boston, MA 02115. Email: dborsook{at}mclean.harvard.edu




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A. Lebel, L. Becerra, D. Wallin, E. A. Moulton, S. Morris, G. Pendse, J. Jasciewicz, M. Stein, M. Aiello-Lammens, E. Grant, et al.
fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children
Brain, July 1, 2008; 131(7): 1854 - 1879.
[Abstract] [Full Text] [PDF]



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