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.
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