A convergence of data from research in animals and humans indicates that nerve damage may cause alterations in central nervous system circuitry. The trigeminal system offers unique advantages for studying nerve injury-induced CNS plasticity in human subjects, including its large central representation, high degree of somatotopy, and the relative symptomatic homogeneity of patients suffering pain and/or sensory loss following trigeminal nerve damage. The objective of this study is to use quantitative sensory testing and functional magnetic resonance imaging (fMRI) to measure CNS plasticity in the trigeminal system (spinal nucleus of fifth nerve, thalamus, and primary somatosensory cortex) under conditions of increased (hyperalgesia/allodynia) somatosensory input in healthy volunteers and in patients with trigeminal nerve damage. We will test the following hypotheses: (a) noxious thermal stimuli to the three division (V1, V2, V3) of the trigeminal nerve will produce activation in trigeminal sensory pathways; (b) capsaicin induced experimental hyperalgesia, or (c) allodynia in neuropathic pain patients will produce an increase in signal to non-noxious stimuli; and, (d) partial ablation of the trigeminal ganglion for therapeutic reasons will result in a progressive change in the CNS response to mechanical and thermal stimuli. In preliminary imaging studies we found that painful stimuli of the periorbital skin increases the BOLD signal in the trigeminal system at all three levels; that innocuous mechanical stimuli applied to the capsaicin-induced hyperalgesic skin increases fMRI signal in the spV and thalamus; and that allodynia to brush or thermal stimuli in patients activate both spV and the thalamus. This grant proposal offers a unique collaborative effort combining expertise from the fields of pain imaging, neurophysiology and quantitative sensory testing to examine CNS plasticity in the trigeminal system. These studies will elucidate whether CNS plasticity plays a role in the pathogenesis or expression of neuropathic pain and potentially allow an objective measurement of sensory changes in patients with chronic pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042721-05
Application #
7467973
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Porter, Linda L
Project Start
2004-09-15
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2010-06-30
Support Year
5
Fiscal Year
2008
Total Cost
$346,182
Indirect Cost
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Pendse, Gautam; Borsook, David; Becerra, Lino (2009) Enhanced false discovery rate using Gaussian mixture models for thresholding fMRI statistical maps. Neuroimage 47:231-61
Moulton, Eric A; Pendse, Gautam; Morris, Susie et al. (2009) Segmentally arranged somatotopy within the face representation of human primary somatosensory cortex. Hum Brain Mapp 30:757-65
Moulton, E A; Becerra, L; Borsook, D (2009) An fMRI case report of photophobia: activation of the trigeminal nociceptive pathway. Pain 145:358-63
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Becerra, L; Harris, W; Joseph, D et al. (2008) Diffuse optical tomography of pain and tactile stimulation: activation in cortical sensory and emotional systems. Neuroimage 41:252-9
DaSilva, Alexandre F; Becerra, Lino; Pendse, Gautam et al. (2008) Colocalized structural and functional changes in the cortex of patients with trigeminal neuropathic pain. PLoS One 3:e3396
Upadhyay, Jaymin; Knudsen, Jamie; Anderson, Julie et al. (2008) Noninvasive mapping of human trigeminal brainstem pathways. Magn Reson Med 60:1037-46
Becerra, Lino; Borsook, David (2008) Signal valence in the nucleus accumbens to pain onset and offset. Eur J Pain 12:866-9
Borsook, D (2007) Pain and motor system plasticity. Pain 132:8-9
Moulton, Eric A; Pendse, Gautam; Morris, Susie et al. (2007) Capsaicin-induced thermal hyperalgesia and sensitization in the human trigeminal nociceptive pathway: an fMRI study. Neuroimage 35:1586-600

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