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  • Print publication year: 2010
  • Online publication date: October 2010

7 - Peripheral and central mechanisms and manifestations of chronic pain and sensitization


Neuropathic pain is pain following a disease or injury to the nervous system, and can be categorized by the location of the causative injury. Chronic pain following injury of the peripheral nervous system, distal to the oligodendroglial cell – Schwann cell junction, can be termed deafferentation pain or peripheral neuropathic pain. Chronic pain “associated with lesions of the CNS” is termed central pain syndrome (Merskey, 1986; Bonica, 1991). There are many situations in which there is injury of both the peripheral and central nervous system, particularly with injuries of the conus medullaris. In this chapter we will consider primate neuropathic pain states, beginning with peripheral neuropathic or deafferentation syndromes, and concluding with central pain syndromes.

In general terms, both central and peripheral chronic pain syndromes have similar characteristics. These include evidence of sensory loss, ongoing pain and pain evoked by stimuli that are not normally painful (allodynia or hyperalgesia). The sensory loss and hypersensitivity are demonstrated by quantitative sensory testing (QST). In addition, a number of primate models have been developed which mimic the sensory abnormalities in patients with neuropathic pain.

Clinical characteristics of peripheral neuropathic pain

The cause of most neuropathies is based on the medical history, supported by laboratory investigations (Casey et al., 1996b). Diabetes is the most common cause of painful neuropathy. Generally, a progressive course suggests an inherited, metabolic or recurrent toxic etiology.

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Albe-Fessard, D. G., Rampin, O. (1991) Neurophysiological studies in rats deafferented by dorsal root sections. In Deafferentation Pain Syndromes: Pathophysiology and Treatment (Nashold, B. S., Ovelmen-Levitt, J., eds), pp. 125–139. New York: Raven Press.
Ali, Z., Meyer, R. A., Belzberg, A. J. (1999a) Neuropathic pain after C7 spinal nerve transection in man. Pain 96: 41–47.
Ali, Z., Ringkamp, M., Hartke, T. al. (1999b) Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey. J Neurophysiol 81: 455–466.
Andersen, G., Vestergaard, K., Ingeman-Nielsen, M., Jensen, T. S. (1995) Incidence of central post-stroke pain. Pain 61: 187–193.
Apkarian, A. V., Bushnell, M. C., Treede, R.-D., Zubieta, J. K. (2005) Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 9: 463–484.
Archer, A. G., Watkins, P. J., Thomas, P. K., Aharma, A. K., Payan, J. (1983) The natural history of acute painful neuropathy in diabetes mellitus. J Neurol Neurosurg Psychiatry 46: 491–499.
Baron, R., Baron, Y., Disbrow, E., Roberts, T. P. (1999a) Brain processing of capsaicin-induced secondary hyperalgesia: a functional MRI study. Neurology 53: 548–557.
Baron, R., Levine, J. D., Fields, H. L. (1999b) Causalgia and reflex sympathetic dystrophy: does the sympathetic nervous system contribute to the generation of pain?Muscle Nerve 22: 678–695.
Baron, R.Wasner, G., Borgstedt, al. (1999c) Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation. Neurology 52: 923–932.
Bassetti, C., Bogousslavsky, J., Regli, F. (1993) Sensory syndromes in parietal stroke. Neurology 43: 1942–1949.
Baumann, T. K., Simone, D. A., Shain, C. N., Lamotte, R. H. (1991) Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia. J Neurophysiol 66: 212–227.
Baumgartner, U., Tiede, W., Treede, R. D., Craig, A. D. (2006) Laser-evoked potentials are graded and somatotopically organized anteroposteriorly in the operculoinsular cortex of anesthetized monkeys. J Neurophysiol 96: 2802–2808.
Bennett, G. J. (1999) Does a neuroimmune interaction contribute to the genesis of painful peripheral neuropathies?Proc Natl Acad Sci USA 96: 7737–7738.
Bennett, G. J., Xie, Y. K. (1988) A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33: 87–107.
Beric, A., Dimitrijevic, M. R., Lindblom, U. (1988) Central dysesthesia syndrome in spinal cord injury patients. Pain 34: 109–116.
Biemond, A. (1956) The conduction of pain above the level of the thalamus opticus. Arch Neurol Psychiatry 75: 231–244.
Bini, G., Cruccu, G., Hagbarth, al. (1984) Analgesic effect of vibration and cooling on pain induced by electrical stimulation. Pain 18: 239–248.
Blomqvist, A., Ericson, A. C., Craig, A. D., Broman, J. (1996) Evidence for glutamate as a neurotransmitter in spinothalamic tract terminals in the posterior region of owl monkeys. Exp Brain Res 108: 33–44.
Blomqvist, A., Zhang, E. T., Craig, A. D. (2000) Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus. Brain 123: 601–619.
Blumberg, H., Hoffmann, U., Mohadjer, M., Scheremet, R. (1997) Sympathetic nervous system and pain: a clinical reappraisal. Behav Brain Sci 20: 426–434.
Bogousslavsky, J., Regli, F., Uske, A. (1988) Thalamic infarcts: clinical syndromes, etiology and prognosis. Neurology 38: 837–848.
Boivie, J. (1994) Central pain. In Textbook of Pain (Wall, P. D., Melzack, R., eds), pp. 871–902. Edinburgh: Churchill Livingstone.
Boivie, J. (1999) Central pain. In Textbook of Pain (Wall, P. D., Melzack, R., eds), pp. 879–914. Edinburgh: Churchill Livingstone.
Boivie, J. (2006) Central post-stoke pain. In Pain (Cervero, F., Jensen, T. S., eds), pp. 715–730. Edinburgh: Elsevier.
Boivie, J., Leijon, G. (1991) Clinical findings in patients with central poststroke pain. In Pain and Central Nervous System Disease (Casey, K. L., ed.), pp. 65–75. New York: Raven Press.
Boivie, J., Leijon, G., Johansson, I. (1989) Central post-stroke pain – a study of the mechanisms through analyses of the sensory abnormalities. Pain 37: 173–185.
Bonica, J. J. (1991) Introduction: semantic, epidemiologic and educational issues. In Pain and Central Nervous System Disease: The Central Pain Syndromes (Casey, K. L., ed.), pp. 13–29. New York: Raven Press.
Bowsher, D. (1988) Contralateral mirror-image pain following anterolateral cordotomy. Pain 33: 63–65.
Bowsher, D. (1996) Central pain: clinical and physiological characteristics. J Neurol Neurosurg Psychiatry 61: 62–69.
Bowsher, D., Miles, J. B., Haggett, C. E., Eldridge, P. R. (1997) Trigeminal neuralgia: a quantitative sensory perception threshold study in patients who had not undergone previous invasive procedures. J Neurosurg 86: 190–192.
Bowsher, D., Leijon, G., Thuomas, K. A. (1998) Central poststroke pain: correlation of MRI with clinical pain characteristics and sensory abnormalities. Neurology 51: 1352–1358.
Cahana, A., Carota, A., Montadon, M. L., Annoni, J. M. (2004) The long-term effect of repeated intravenous lidocaine on central pain and possible correlation in positron emission tomography measurements. Anesth Analg 98: 1581–1584.
Calford, M. B., Tweedale, R. (1991) Acute changes in cutaneous receptive fields in primary somatosensory cortex after digit denervation in adult flying fox. J Neurophysiol 65: 178–187.
Campbell, J. N., Meyer, R. A. (2006) Mechanisms of neuropathic pain. Neuron 52: 77–92.
Canavero, S., Bonicalzi, V. (1998) The neurochemistry of central pain: evidence from clinical studies, hypothesis and therapeutic implications. Pain 74: 109–114.
Carlton, S. M., McNeill, D. L., Chung, K., Coggeshall, R. E. (1988) Organization of calcitonin gene-related peptide-immunoreactive terminals in the primate dorsal horn. J Comp Neurol 276: 527.
Carlton, S. M., Lekan, H. A., Kim, S. H., Chung, J. M. (1994) Behavioral manifestations of an experimental model for peripheral neuropathy produced by spinal nerve ligation in the primate. Pain 56: 155–166.
Carlton, S. M., Rees, H., Gondesen, K., Willis, W. D. (1997) Dextrorphan attenuates responses of spinothalamic tract cells in normal and nerve-injured monkeys. Neurosci Lett 229: 169–172.
Carlton, S. M., Rees, H., Tsuruoka, M., Willis, W. D. (1998) Memantine attenuates responses of spinothalamic tract cells to cutaneous stimulation in neuropathic monkeys. Eur J Pain 2: 229–238.
Casey, K. L. (2007) Pathophysiology of central poststroke pain: the contribution of functional imaging and a hypothesis. In Central Neuropathic Pain: Focus on Poststroke Pain (Henry, J. L., Panju, A., Yashpal, K., eds), pp. 115–131. Seattle: IASP Press.
Casey, K. L., Zumberg, M., Heslep, H., Morrow, T. J. (1993) Afferent modulation of warmth sensation and heat pain in the human hand. Somatosens Mot Res 10: 327–337.
Casey, K. L., Beydoun, A., Boivie, al. (1996a) Laser-evoked cerebral potentials and sensory function in patients with central pain. Pain 64: 485–491.
Casey, K. L., Gonzalez, J. P., Max, M. al. (1996b) Pain. In Learning in Neurology (Munsat, T. L., Muncat, T. L., eds), Baltimore: Williams & Williams.
Casey, K. L., Lorenz, J., Minoshima, S. (2003) Insights into the pathophysiology of neuropathic pain through functional brain imaging. Exp Neurol 184: 80–88.
Cassinari, V., Pagni, C. A. (1969) Central pain. A Neurosurgical Survey. Cambridge, MA: Harvard University Press.
Cerne, R., Rusin, K. I., Randic, M. (1993) Enhancement of the N-methyl-D-aspartate response in spinal dorsal horn neurons by cAMP-dependent protein kinase. Neurosci Lett 161: 124–128.
Cesaro, P., Mann, M. W., Moretti, J. al. (1991) Central pain and thalamic hyperactivity: a single photon emission computerized tomographic study. Pain 47: 329–336.
Chung, J. M., Leem, J. W., Kim, S. H. (1992) Somatic afferent fibers which continuously discharge after being isolated from their receptors. Brain Res 599: 29–33.
Coggeshall, R. E., Hong, K. A. P., Langford, L. A., Schaible, H. G., Schmidt, R. F. (1983) Discharge characteristics of fine medial articular afferents at rest and during passive movements of inflamed knee joints. Brain Res 272: 185–188.
Coghill, R. C., Gilron, I., Iadarola, M. J. (2001) Hemispheric lateralization of somatosensory processing. J Neurophysiol 85: 2602–2612.
Cohen, S., Abdi, S. (2002) Central pain. Curr Opin Anaesthesiol 15: 575–581.
Collingridge, G. L., Bliss, T. V. P. (1987) NMDA receptors – their role in long-term potentiation. Trends Neurosci 10: 288–293.
Collingridge, G. L., Watkins, J. C. eds. (1994) The NMDA Receptor, 2nd ed., Oxford: Oxford University Press.
Cook, D. B., Lange, G., Ciccone, D. al. (2004) Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol 31: 364–378.
Cox, J. J., Reimann, F., Nicholas, A. al. (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444: 894–898.
Craig, A. D. (1998) A new version of the thalamic disinhibition hypothesis of central pain. Pain Forum 7: 1–14.
Craig, A. D. (2000) The functional anatomy of lamina I and its role in post-stroke central pain. In Nervous System Plasticity and Chronic Pain (Sandkühler, J., Bromm, B., Gebhart, G. F., eds), pp. 137–151. Amsterdam: Elsevier.
Craig, A. D. (2003) Pain mechanisms: labeled lines versus convergence in central processing. Ann Rev Neurosci 26: 1–30.
Craig, A. D. (2008) Can the basis for central neuropathic pain be identified by using a thermal grill?Pain 135: 215–216.
Craig, A. D., Bushnell, M. C. (1994) The thermal grill illusion: unmasking the burn of cold pain. Science 265: 252–255.
Craig, A. D., Reiman, E. M., Evans, A., Bushnell, M. C. (1996) Functional imaging of an illusion of pain. Nature 384: 258–260.
Cruccu, G., Leandri, M., Feliciani, M., Manfredi, M. (1990) Idiopathic and symptomatic trigeminal pain. J Neurol Neurosurg Psychiatry 53: 1034–1042.
Davidoff, G., Roth, E. (1991) Clinical characteristics of central (dysesthetic) pain syndrome in spinal cord injury patients. In Pain and Central Nervous System Diseases: The Central Pain Syndromes (Casey, K. L., ed.), pp. 77–83. New York: Raven.
Davis, K. D., Kiss, Z. H. T., Tasker, R. R., Dostrovsky, J. O. (1996) Thalamic stimulation-evoked sensations in chronic pain patients and nonpain (movement disorder) patients. J Neurophysiol 75: 1026–1037.
Davis, K. D., Kiss, Z. H., Luo, al. (1998a) Phantom sensations generated by thalamic microstimulation. Nature 391: 385–387.
Davis, K. D., Kwan, C. L., Crawley, A. P., Mikulis, D. J. (1998b) Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli. J Neurophysiol 80: 1533–1546.
Davis, K. D., Lozano, R. M., Manduch, al. (1999) Thalamic relay site for cold perception in humans. J Neurophysiol 81: 1970–1973.
Defrin, R., Ohry, A., Blumen, N., Urca, G. (1999) Acute pain threshold in subjects with chronic pain following spinal cord injury. Pain 83: 275–282.
Defrin, R., Ohry, A., Blumen, N., Urca, G. (2002) Sensory determinants of thermal pain. Brain 125: 501–510.
Dejerine, J., Roussy, G. (1906) La syndrome thalamique. Rev Neurol 14: 521–532.
Diatchenko, L., Slade, G. D., Nackley, A. al. (2005) Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet 14: 135–143.
DiPiero, V., Jones, A. K. P., Iannotti, al. (1991) Chronic pain: a PET study of the central effects of percutaneous high cervical cordotomy. Pain 46: 9–12.
Djouhri, L., Koutsikou, S., Fang, X., McMullan, S., Lawson, S. N. (2006) Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J Neurosci 26: 1281–1292.
Donovan, W. H., Dimitrijevic, M. R., Dahm, al. (1982) Neurophysiological approaches to chronic pain following spinal cord injury. Paraplegia 20: 135–146.
Dostrovsky, J. O., Craig, A. D. (1996) Cooling-specific spinothalamic neurons in the monkey. J Neurophysiol 76: 3656–3665.
Dostrovsky, J. O., Wells, F. E. B., Tasker, R. R. (1991) Pain evoked by stimulation in human thalamus. In International Symposium on Processing Nociceptive Information (Sjigenaga, Y., ed.), pp. 115–120. Amsterdam: Elsevier.
Dougherty, P. M., Willis, W. D. (1991) Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined microiontophoretic application of N-methyl-D-aspartic acid and substance P. Pain 47: 85–93.
Dougherty, P. M., Willis, W. D. (1992) Enhanced responses of spinothalamic tract neurons to excitatory amino acids accompany capsaicin-induced sensitization in the monkey. J Neurosci 12: 883–894.
Dougherty, P. M., Palecek, J., Paleckova, V., Sorkin, L. S., Willis, W. D. (1992) The role of NMDA and non-NMDA excitatory amino acid receptors in the excitation of primate spinothalamic tract neurons by mechanical, thermal, chemical and electrical stimuli. J Neurosci 12: 3025–3041.
Dougherty, P. M., Palecek, J., Zorn, S., Willis, W. D. (1993) Combined application of excitatory amino acids and substance P produces long-lasting changes in responses of primate spinothalamic tract neurons (1993). Brain Res Rev 18: 227–246.
Dougherty, P. M., Palecek, J., Paleckova, V., Willis, W. D. (1994) Neurokinin 1 and 2 antagonists attenuate the resonses and NK1 antagonists prevent the sensitization of primate spinothalamic tract neurons after intradermal capsaicin. J Neurophysiol 72: 1464–1475.
Dougherty, P. M., Palecek, J., Paleckova, V., Willis, W. D. (1995) Infusion of substance P or neurokinin A by microdialysis alters responses of primate spinothalamic tract neurons to cutaneous stimuli and to iontophoretically released excitatory amino acids. Pain 61: 411–425.
Dougherty, P. M., Li, Y. J., Lenz, F. A., Rowland, L., Mittman, S. (1996) Evidence that excitatory amino acids mediate afferent input to the primate somatosensory thalamus. Brain Res 278: 267–273.
Dray, A., Bettaney, J., Forster, P., Perkins, M. N. (1988) Bradykinin-induced stimulation of afferent fibres is mediated through protein kinase C. Neurosci Lett 91: 301–307.
Dubner, R., Ren, K. (1999) Endogenous mechanisms of sensory modulation. Pain Suppl 6: S45–S53.
Ducreux, D., Attal, N., Parker, F., Bouhassira, D. (2006) Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain 129: 963–976.
Duncan, G. H., Bushnell, M. C., Oliveras, J. L., Bastrash, N., Tremblay, N. (1993) Thalamic VPM nucleus in the behaving monkey. III. Effects of reversible inactivation by lidocaine on thermal and mechanical discrimination. J Neurophysiol 70: 2086–2096.
Duggan, A. W., Hendry, I. A., Morton, C. R., Hutchison, W. D., Zhao, Z. Q. (1988) Cutaneous stimuli releasing immunoreactive substance P in the dorsal horn of the cat. Brain Res 451: 261–273.
Duggan, A. W., Hope, P. J., Jarrott, B., Schaible, H. G., Fleetwood-Walker, S. M. (1990) Release, spread and persistence of immunoreactive neurokinin A in the dorsal horn of the cat following noxious cutaneous stimulation. Studies with antibody microprobes. Neuroscience 35: 195–202.
Dyck, P. J., Lambert, E. H., O'Brien, P. C. (1976) Pain in peripheral neuropathy related to rate and kind of fiber degeneration. Neurology 26: 466–471.
Dykes, R. W., Terzis, J. K. (1979) Reinnervation of glabrous skin in baboons: properties of cutaneous mechanoreceptors subsequent to nerve crush. J Neurophysiol 42: 1461–1478.
Eaton, S. A., Salt, T. E. (1990) Thalamic NMDA receptors and nociceptive sensory synaptic transmission. Neurosci Lett 110: 297–302.
Edwards, R. R. (2005) Individual differences in endogenous pain modulation as a risk factor for chronic pain. Neurology 65: 437–443.
Eide, P. K. (1998) Pathophysiological mechanisms of central neuropathic pain after spinal cord injury. Spinal Cord 36: 601–612.
Eide, P. K., Rabben, T. (1998) Trigeminal neuropathic pain: pathophysiological mechanisms examined by quantitative assessment of abnormal pain and sensory perception. Neurosurgery 43: 1103–1109.
England, J. D., Happel, L. T., Kline, D. al. (1996) Sodium channel accumulation in humans with painful neuromas. Neurology 47: 272–276.
Ericson, A. C., Blomqvist, A., Craig, A. D., Ottersen, O. P., Broman, J. (1993) Enrichment of glutamate-like immunoreactivity in spinothalamic tract terminals in the nucleus submedius of cat. Soc Neurosci Abstr 18: 832.
Fang, L., Wu, J., Lin, Q., Willis, W. D. (2002) Calcium–calmodulin dependent protein kinase II contributes to spinal cord central sensitization. J Neuroscience 22: 4196–4204.
Fang, L., Wu, J., Lin, Q., Willis, W. D. (2003a) Protein kinases regulate the phosphorylation of the GluR1 subunit of AMPA receptors of spinal cord in rats following noxious stimulation. Brain Res Mol Brain Res 118: 160–165.
Fang, L., Wu, J., Zhang, X., Lin, Q., Willis, W. D. (2003b) Increased phosphorylation of the GluR1 subunit of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor in rats following intradermal injection of capsaicin. Neuroscience 122: 237–245.
Fang, L., Wu, J., Zhang, X., Lin, Q., Willis, W. D. (2005) Calcium/calmodulin dependent protein kinase II regulates the phosphorylation of cyclic AMP-responsive element-binding protein of spinal cord in rats following noxious stimulation. Neurosci Lett 374: 1–4.
Fenollosa, P., Pallares, J., Cervera, al. (1993) Chronic pain in the spinal cord injured: statistical approach and pharmacological treatment. Paraplegia 31: 722–729.
Ferrington, D. G., Sorkin, L. S., Willis, W. D. (1986) Responses of spinothalamic tract cells in the cat cervical spinal cord to innocuous and graded noxious stimuli. Somatosens Res 3: 339–358.
Fertleman, C. R., Baker, M. D., Parker, K. al. (2006) SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 52: 767–774.
Finnerup, N. B., Johannesen, I. L., Bach, F. W., Jensen, T. S. (2003a) Sensory function above lesion level in spinal cord injury patients with and without pain. Somatosens Mot Res 20: 71–76.
Finnerup, N. B., Johannesen, I. L., Fuglsang-Frederiksen, A., Bach, F. W., Jensen, T. S. (2003b) Sensory function in spinal cord injury patients with and without central pain. Brain 126: 57–70.
Fitzek, S., Baumgärtner, U., Fitzek, al. (2001) Mechanisms and predictors of chronic facial pain in lateral medullary infarction. Ann Neurol 49: 493–500.
Flor, H., Elbert, T., Knecht, al. (1995) Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375: 482–484.
Florence, S. L., Taub, H. B., Kaas, J. H. (1998) Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys. Science 282: 1117–1121.
Fukuhara, T., McKhann, G. M.., Santiago, al. (1999) Resolution of central pain after embolization of an arteriovenous malformation – case report. J Neurosurg 90: 575–579.
Fukumoto, M., Ushida, T., Zinchuk, V. S., Yamamoto, H., Yoshida, S. (1999) Contralateral thalamic perfusion in patients with reflex sympathetic dystrophy syndrome. Lancet 354: 1790–1791.
Garcia-Larrea, L., Convers, P., Magnin, al. (2002) Laser-evoked potential abnormalities in central pain patients: the influence of spontaneous and provoked pain. Brain 125: 2766.
Geha, P. Y., Baliki, M. N., Chialvo, D. al. (2007) Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy. Pain 128: 88–100.
Geisser, M. E., Casey, K. L., Brucksch, C. al. (2003) Perception of noxious and innocuous heat stimulation among healthy women and women with fibromyalgia: association with mood, somatic focus, and catastrophizing. Pain 102: 243–250.
Gorson, K. C., Herrmann, D. N., Thiagarajan, al. (2008) Non-length dependent small fibre neuropathy/ganglionopathy. J Neurol Neurosurg Psychiatry 79: 163–169.
Gracely, R. H., Lynch, S. A., Bennett, G. J. (1992) Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 51: 175–194.
Gracely, R. H., Petzke, F., Wolf, J. M., Clauw, D. J. (2002) Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 46: 1333–1343.
Gracely, R. H., Geisser, M. E., Giesecke, al. (2004) Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain 127: 835–843.
Green, B. G., Roman, C., Schoen, K., Collins, H. (2008) Nociceptive sensations evoked from “spots” in the skin by mild cooling and heating. Pain 135: 196–208.
Greenspan, J. D., Winfield, J. A. (1992) Reversible pain and tactile deficits associated with a cerebral tumor compressing the posterior insula and parietal operculum. Pain 50: 29–39.
Greenspan, J. D., Ohara, S., Sarlani, E., Lenz, F. A. (2004) Allodynia in patients with post-stroke central pain (CPSP) studied by statistical quantitative sensory testing within individuals. Pain 109: 357–366.
Greenspan, J. D., Coghill, R. C., Gilron, al. (2008a) Quantitative somatic sensory testing and functional imaging of the response to painful stimuli before and after cingulotomy for obsessive compulsive disorder (OCD). Eur J Pain doi:10.1016/ejpain_2008.01.007.
Greenspan, J. D., Treede, R. D., Tasker, R. R., Lenz, F. A. (2008b) Central pain. In Bonica's Management of Pain (Yaksh, T. L., ed.). New York: Lippincott Williams & Wilkins.
Guenther, S., Reeh, P. W., Kress, M. (1999) Rises in [Ca2+]i mediate capsaicin- and proton-induced heat sensitization of rat primary nociceptive neurons. Eur J Neurosci 11: 3143–3150.
Hains, B. C., Saab, C. Y., Waxman, S. G. (2006) Alterations in burst firing of thalamic VPL neurons and reversal by Na(v)1.3 antisense after spinal cord injury. J Neurophysiol 95: 3343–3352.
Halliday, A. M., Logue, V. (1972) Painful sensations evoked by electrical stimulation in the thalamus. In Neurophysiology Studied in Man (Somjen, G. G., ed.), pp. 221–230. Amsterdam: Excerpta Medica.
Han, H. C., Lee, D. H., Chung, J. M. (2000) Characteristics of ectopic discharges in a rat neuropathic pain model. Pain 84: 253–261.
Hardy, J. D., Wolff, H. G., Goodell, H. (1967) Pain Sensations and Reactions. New York: Hafner Publishing Co.
Harris, R. E., Clauw, D. J., Scott, D. al. (2007) Decreased central μ-opioid receptor availability in fibromyalgia. J Neurosci 27: 10000–10006.
Hassler, R. (1970) Dichotomy of facial pain conduction in the diencephalon. In Trigeminal Neuralgia (Walker, A. E., ed.), pp. 123–138. Philadelphia: W.B. Saunders.
Hassler, R., Reichert, T. (1959) Klinische und anatomische Befunde bei stereotaktischen Schmerzoperationen im Thalamus. Arch Psychiat Nerverkr 200: 93–122.
Hecaen, H., Talairach, J., David, M., Dell, M. B. (1949) Coagulations limitees du thalamus dans les algies du syndrome thalamique. Resultats therapeutiques et physiologiques. Rev Neurolog 81: 68–93.
Hilton, D. A., Love, S., Gradidge, T., Coakham, H. B. (1994) Pathological findings associated with trigeminal neuralgia caused by vascular compression. Neurosurgery 35: 299–303.
Hirai, T., Jones, E. G. (1989) A new parcellation of the human thalamus on the basis of histochemical staining. Brain Res Rev 14: 1–34.
Hirato, M., Kawashima, Y., Shibazaki, T., Shibasaki, T., Ohye, C. (1991) Pathophysiology of central (thalamic) pain: a possible role of the intralaminar nuclei in superficial pain. Acta Neurochir Suppl (Wien) 52: 133–136.
Hirato, M., Horikoshi, S., Kawashima, al. (1993) The possible role of the cerebral cortex adjacent to the central sulcus for the genesis of central (thalamic) pain – a metabolic study. Acta Neurochir Suppl (Wien) 58: 141–144.
Hirato, M., Watanabe, K., Takahashi, al. (1994) Pathophysiology of central (thalamic) pain: combined change of sensory thalamus with cerebral cortex around central sulcus. Stereotact Funct Neurosurg 62: 300–303.
Hirayama, T., Dostrovsky, J. O., Gorecki, J., Tasker, R. R., Lenz, F. A. (1989) Recordings of abnormal activity in patients with deafferentation and central pain. Stereotact Funct Neurosurg 52: 120–126.
Holland, N. R., Crawford, T. O., Hauer, al. (1998) Small-fiber sensory neuropathies: clinical course and neuropathology of idiopathic cases. Ann Neurol 44: 47–59.
Hsieh, J. C., Belfrage, M., Stone-Elander, S., Hansson, P., Ingvar, M. (1995) Central representation of chronic ongoing neuropathic pain studied by positron emission tomography. Pain 63: 225–236.
Iadarola, M. J., Max, M. B., Berman, K. al. (1995) Unilateral decrease in thalamic activity observed with PET in patients with chronic neuropathic pain. Pain 63: 55–64.
Iadarola, M. J., Berman, K. F., Zeffiro, T. al. (1998) Neural activation during acute capsaicin-evoked pain and allodynia assessed with PET. Brain 121: 931–947.
Jahnsen, H., Llinas, R. (1984a) Electrophysiological properties of guinea-pig thalamic neurones: an in vitro study. J Physiol 349: 205–226.
Jahnsen, H., Llinas, R. (1984b) Ionic basis for the electro-responsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J Physiol 349: 227–247.
Jones, A. K., Watabe, H., Cunningham, V. J., Jones, T. (2004) Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET. Eur J Pain 8: 479–485.
Jones, E. G. (1985) The Thalamus. New York: Plenum.
Jones, E. G. (1993) GABAergic neurons and their role in cortical plasticity in primates. Cereb Cortex 3: 361–372.
Jones, E. G. (2002) Thalamic circuitry and thalamocortical synchrony. Phil Trans R Soc Lond B 357: 1659–1673.
Jones, E. G., Pons, T. P. (1998) Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex. Science 282: 1121–1125.
Kenshalo, D. R., Leonard, R. B., Chung, J. M., Willis, W. D. (1979) Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli. J Neurophysiol 42: 1370–1389.
Kenshalo, D. R., Leonard, R. B., Chung, J. M., Willis, W. D. (1982) Facilitation of the response of primate spinothalamic cells to cold and to tactile stimuli by noxious heating of the skin. Pain 12: 141–152.
Khedr, E. M., Kotb, H., Kamel, N. al. (2005) Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry 76: 833–838.
Kilgard, M. P., Merzenich, M. M. (1998) Cortical map reorganization enabled by nucleus basalis activity. Science 279: 1714–1718.
Kim, J. H., Greenspan, J. D., Coghill, R. C., Ohara, S., Lenz, F. A. (2007) Lesions limited to the human thalamic principal somatosensory nucleus (ventral caudal) are associated with loss of cold sensations and central pain. J Neurosci 27: 4995–5004.
Kim, J. S. (2003) Central post-stroke pain or paresthesia in lenticulo-capsular hemorrhages. Neurology 61: 679–682.
Kim, J. S. (2007) Patterns of sensory abnormality in cortical stroke: evidence for a dichotomized sensory system. Neurology 68: 174–180.
Kim, J. S., Choi-Kwon, S. (1999) Sensory sequelae of medullary infarction – differences between lateral and medial medullary syndrome. Stroke 30: 2697–2703.
Kim, S. H., Chung, J. M. (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50: 355–364.
Klun, B. (1992) Microvascular decompression and partial sensory rhizotomy in the treatment of trigeminal neuralgia: personal experience with 220 patients. Neurosurgery 30: 49–52.
Koltzenburg, M., Bennett, D. L., Shelton, D. L., McMahon, S. B. (1999) Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin. Eur J Neurosci 11: 1698–1704.
Koschorke, G. M., Meyer, R. A., Tillman, D. B., Campbell, J. N. (1991) Ectopic excitability of injured nerves in monkey: entrained responses to vibratory stimuli. J Neurophysiol 65: 693–701.
Kress, M., Guenther, S. (1999) Role of [Ca2+]i in the ATP-induced heat sensitization process of rat nociceptive neurons. J Neurophysiol 81: 2612–2619.
Lahuerta, J., Bowsher, D., Lipton, S., Buxton, P. H. (1994) Percutaneous cervical cordotomy: a review of 181 operations on 146 patients with a study on the location of “pain fibers” in the C-2 spinal cord segment of 29 cases. J Neurosurg 80: 975–985.
Lamotte, R. H., Thalhammer, J. G., Robinson, C. J. (1983) Peripheral neural correlates of magnitude of cutaneous pain and hyperalgesia: a comparison of neural events in monkey with sensory judgments in human. J Neurophysiol 50: 1–26.
Lamotte, R. H., Shain, C. N., Simone, D. A., Tsai, E.-F. P. (1991) Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. J Neurophysiol 66: 190–211.
Lamotte, R. H., Lundberg, L. E., Torebjork, H. E. (1992) Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol 448: 749–764.
Lee, J., Dougherty, P. M., Antezana, D., Lenz, F. A. (1999) Responses of neurons in the region of human thalamic principal somatic sensory nucleus to mechanical and thermal stimuli graded into the painful range. J Comp Neurol 410: 541–555.
Leijon, G., Boivie, J., Johansson, I. (1989) Central post-stroke pain – neurological symptoms and pain characteristics. Pain 36: 13–25.
Lenz, F. A., Byl, N. N. (1999) Reorganization in the cutaneous core of the human thalamic principal somatic sensory nucleus (ventral caudal) in patients with dystonia. J Neurophysiol 82: 3204–3212.
Lenz, F. A., Tasker, R. R., Dostrovsky, J. al. (1987) Abnormal single-unit activity recorded in the somatosensory thalamus of a quadriplegic patient with central pain. Pain 31: 225–236.
Lenz, F. A., Dostrovsky, J. O., Tasker, R. al. (1988) Single-unit analysis of the human ventral thalamic nuclear group: somatosensory responses. J Neurophysiol 59: 299–316.
Lenz, F. A., Kwan, H. C., Dostrovsky, J. O., Tasker, R. R. (1989) Characteristics of the bursting pattern of action potentials that occurs in the thalamus of patients with central pain. Brain Res 496: 357–360.
Lenz, F. A., Seike, M., Lin, Y. al. (1993a) Neurons in the area of human thalamic nucleus ventralis caudalis respond to painful heat stimuli. Brain Res 623: 235–240.
Lenz, F. A., Seike, M., Richardson, R. al. (1993b) Thermal and pain sensations evoked by microstimulation in the area of human ventrocaudal nucleus. J Neurophysiol 70: 200–212.
Lenz, F. A., Gracely, R. H., Rowland, L. H., Dougherty, P. M. (1994a) A population of cells in the human thalamic principal sensory nucleus respond to painful mechanical stimuli. Neurosci Lett 180: 46–50.
Lenz, F. A., Kwan, H. C., Martin, al. (1994b) Characteristics of somatotopic organization and spontaneous neuronal activity in the region of the thalamic principal sensory nucleus in patients with spinal cord transection. J Neurophysiol 72: 1570–1587.
Lenz, F. A., Gracely, R. H., Baker, F. H., Richardson, R. T., Dougherty, P. M. (1998a) Reorganization of sensory modalities evoked by microstimulation in region of the thalamic principal sensory nucleus in patients with pain due to nervous system injury. J Comp Neurol 399: 125–138.
Lenz, F. A., Rios, M., Chau, al. (1998b) Painful stimuli evoke potentials recorded from the parasylvian cortex in humans. J Neurophysiol 80: 2077–2088.
Lenz, F. A., Ohara, S., Gracely, R. H., Dougherty, P. M., Patel, S. H. (2004) Pain encoding in the human forebrain: binary and analog exteroceptive channels. J Neurosci 24: 6540–6544.
Levitt, M. (1983) The bilaterally symmetrical deafferentation syndrome in macaques after bilateral spinal lesions: evidence for dysesthesias resulting from brain foci and considerations of spinal pain pathways. Pain 16: 167–184.
Levitt, M. (1989) Postcordotomy spontaneous dysesthesias in macaques: recurrence after spinal cord transection. Brain Res 481: 47–56.
Levitt, M., Levitt, J. H. (1981) The deafferentation syndrome in monkeys: dysesthesias of spinal origin. Pain 10: 129–147.
Lin, Q, Peng, Y. B., Willis, W. D. (1996a) Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is reduced during central sensitization. J Neurophysiol 76: 1005–1014.
Lin, Q., Peng, Y. B., Willis, W. D. (1996b) Possible role of protein kinase C in the sensitization of primate spinothalamic tract neurons. J Neurosci 16: 3026–3034.
Lin, Q., Peng, Y. B., Wu, J., Willis, W. D. (1997) Involvement of cGMP in nociceptive processing by and sensitization of spinothalamic neurons in primates. J Neurosci. 17: 3293–3302.
Lin, Q., Palecek, J., Paleckova, al. (1999a) Nitric oxide mediates the central sensitization of primate spinothalamic tract neurons. J Neurophysiol 81: 1075–1085.
Lin, Q., Wu, J., Peng, Y. B., Cui, M., Willis, W. D. (1999b) Inhibition of primate spinothalamic tract neurons by spinal glycine and GABA is modulated by guanosine 3′,5′-cyclic monophosphate. J Neurophysiol 81: 1095–1103.
Lin, Q., Wu, J., Peng, Y. B., Cui, M., Willis, W. D. (1999c) Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons. J Neurophysiol 81: 1086–1094.
Lin, Q., Wu, J., Willis, W. D. (2002) Effects of protein kinase A activation on the responses of primate spinothalamic tract neurons to mechanical stimuli. J Neurophysiol 88: 214–221.
Liu, X. G., Sandkuhler, J. (1995) Long-term potentiation of C-fiber-evoked potentials in the rat spinal dorsal horn is prevented by spinal N-methyl-D-aspartic acid receptor blockage. Neurosci Lett 191: 43–46.
Lopshire, J. C., Nicol, G. D. (1998) The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and single-channel studies. J Neurosci 18: 6081–6092.
Lorenz, J., Kohlhoff, H., Hansen, H. C., Kunze, K., Bromm, B. (1998) Aβ-fiber mediated activation of cingulate cortex as correlate of central post-stroke pain. Neuro report 9: 659–663.
Lorenz, J., Cross, D., Minoshima, al. (2002) A unique representation of heat allodynia in the human brain. Neuron 35: 383–393.
Lorenz, J., Minoshima, S., Casey, K. L. (2003) Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation. Brain 126: 1079–1091.
Lund, J. P., Sun, G. D., Lamarre, Y. (1994) Cortical reorganization and deafferentation in adult macaques. Science 265: 546–548.
MacGowan, D. J. L., Janal, M. N., Clark, M. al. (1997) Central poststroke pain and Wallenberg's lateral medullary infarction: frequency, character, and determinants in 63 patients. Neurology 49: 120–125.
Magistretti, P. J., Pellerin, L., Rothman, D. L., Shulman, R. G. (1999) Energy on demand. Science 283: 496–497.
Maihofner, C., Forster, C., Birklein, F., Neundorfer, B., Handwerker, H. O. (2005) Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study. Pain 114: 93–103.
Maihofner, C., Baron, R., DeCol, al. (2007) The motor system shows adaptive changes in complex regional pain syndrome. Brain 130: 2671–2687.
Malmberg, A. B., Brandon, E. P., Idzerda, R. al. (1997a) Diminished inflammation and nociceptive pain with preservation of neuropathic pain in mice with a targeted mutation of the type I regulatory subunit of cAMP-dependent protein kinase. J Neurosci 17: 7462–7470.
Malmberg, A. B., Chen, C., Tonegawa, S., Basbaum, A. I. (1997b) Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma. Science 278: 279–283.
Mallat, S., Zhang, Z. (1993) Matching pursui with time-frequency dictionaries. IEEE Trans Signal Proc 41: 3397–3415.
Mehler, W. R. (1966) Some observations on secondary ascending afferent systems in the CNS. In Pain (Knighton, R. S., Dumke, P. R., eds), pp. 11–32. Boston: Brown and Little.
Merskey, H. (1986) Classification of chronic pain. Pain Suppl 3: S1–S220.
Meyer, R. A., Raja, S. N., Campbell, J. N., Mackinnon, S. E., Dellon, A. L. (1985) Neural activity originating from a neuroma in the baboon. Brain Res 325: 255–260.
Milne, R. J., Aniss, A. M., Kay, N. E., Gandevia, S. C. (1988) Reduction in perceived intensity of cutaneous stimuli during movement – a quantitative study. Exp Brain Res 70: 569–576.
Mogil, J. S., Grisel, J. E. (1998) Transgenic studies of pain. Pain 77: 107–128.
Moisset, X., Bouhassira, D. (2007) Brain imaging of neuropathic pain. Neuroimage37 (Suppl. 1): S80–S88.
Montes, C., Magnin, M., Maarrawi, al. (2005) Thalamic thermo-algesic transmission: ventral posterior (VP) complex versus VMpo in the light of a thalamic infarct with central pain. Pain 113: 223–232.
Moon, D. E., Lee, D. H., Han, H. al. (1999) Adrenergic sensitivity of the sensory receptors modulating mechanical allodynia in a rat neuropathic pain model. Pain 80: 589–595.
Mountcastle, V. B. (1984) Central nervous mechanisms in mechanoreceptive sensibility. In Handbook of Physiology. Sensory Processes (Brookhart, J. M., Mountcastle, V. B., Smith, I. D., Geiger, S. R., eds), p. 789. Bethesda: American Physiological Society.
Nagaro, T., Amakawa, K., Arai, T., Ochi, G. (1993) Ipsilateral referral of pain following cordotomy. Pain 55: 275–276.
Nagaro, T., Adachi, N., Tabo, E., Kimura, S., Arai, T., Dote, K. (2001) New pain following cordotomy: clinical features, mechanisms, and clinical importance. J Neurosurg 95: 425–431.
Nathan, P. W. (1963) Results of antero-lateral cordotomy for pain in cancer. J Neurol Neurosurg Psychiatry 26: 353–362.
Nathan, P. W., Smith, M. C. (1979) Clinico-anatomical correlation in anterolateral cordotomy. In Advances in Pain Research and Therapy (Bonica, J. J., Liebeskind, J. C., Albe-Fessard, D. G., eds), pp. 921–926. New York: Raven Press.
Nathan, P. W., Smith, M. C. (1996) Some tracts of the anterior and lateral columns of the spinal cord. In Pain (Knighton, R. S., Dumke, P. R., eds), pp. 47–58. Philadelphia: Lippincott, Williams, and Wilkins.
Nathan, P. W., Smith, M. C., Cook, A. W. (1986) Sensory effects in man of lesions of the posterior columns and of some other afferent pathways. Brain 109: 1003–1041.
Ness, T. J., San Pedro, E. C., Richards, J. al. (1998) A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin. Pain 78: 139–143.
Neugebauer, V., Chen, P. S., Willis, W. D. (1999) Role of metabotropic glutamate receptor subtype mGluR1 in brief nociception and central sensitization of primate STT cells. J Neurophysiol 82: 272–282.
Neugebauer, V., Chen, P. S., Willis, W. D. (2000) Groups II and III metabotropic glutamate receptors differentially modulate brief and prolonged nociception in primate STT cells. J Neurophysiol 84: 2998–3009.
Nguyen, J. P., Lefaucher, J. P., Guerinel, al. (2000) Motor cortex stimulation in the treatment of central and neuropathic pain. Arch Med Res 31: 263–265.
Nicholson, B. D. (2004) Evaluation and treatment of central pain syndromes. Neurology 62: S30–S36.
Nilsson, H. J., Schouenborg, J. (1999) Differential inhibitory effect on human nociceptive skin senses induced by local stimulation of thin cutaneous fibers. Pain 80: 103–112.
Nilsson, H. J., Levinsson, A., Schouenborg, J. (1997) Cutaneous field stimulation (CFS): a new powerful method to combat itch. Pain 71: 49–55.
North, R. A. (ed.) (1995) Handbook of Receptors and Channel Ligand- and Voltage-Gated Ion Channels. CRC Press, Boca Raton, 1995.
Nurmikko, T. J. (1991) Altered cutaneous sensation in trigeminal neuralgia. Arch Neurol 48: 523–527.
Nurmikko, T. J., Eldridge, P. R. (2001) Trigeminal neuralgia – pathophysiology, diagnosis and current treatment. Br J Anaesth 87: 117–132.
O'Dell, T. J., Kandel, E. R., Grant, S. G. (1991) Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors. Nature 353: 558–560.
Obermann, M., Yoon, M. S., Ese, al. (2007) Impaired trigeminal nociceptive processing in patients with trigeminal neuralgia. Neurology 69: 835–841.
Ofek, H., Defrin, R. (2007) The characteristics of chronic central pain after traumatic brain injury. Pain 131: 330–340.
Ohara, P. T., Chazal, G., Ralston, H. J. (1989) Ultrastructural analysis of GABA-immunoreactive elements in the monkey thalamic ventrobasal complex. J Comp Neurol 283: 541–558.
Ohara, S., Lenz, F. A. (2003) Medial lateral extent of thermal and pain sensations evoked by microstimulation in somatic sensory nuclei of human thalamus. J Neurophysiol 90: 2367–2377.
Ohara, S., Weiss, N., Lenz, F. A. (2004) Microstimulation in the region of the human thalamic principal somatic sensory nucleus evokes sensations like those of mechanical stimulation and movement. J Neurophysiol 91: 736–745.
Olausson, H., Marchand, S., Bittar, R. al. (2001) Central pain in a hemispherectomized patient. Eur J Pain 5: 209–217.
Osterberg, A., Boivie, J., Thuomas, K.-A. (2005) Central pain in multiple sclerosis – prevalences, clinical characteristics, and mechanisms. Eur J Pain 9: 531–542.
Ovelmen-Levitt, J. (1991) The neurophysiology of deafferentation syndromes. In Deafferentation Pain Syndromes: Pathophysiology and Treatment (Nashold, B. S., Ovelmen-Levitt, J., eds), pp. 103–123. New York: Raven Press.
Ovelmen-Levitt, J., Young, J. N., Rossitch, E. J. R., Nashold, B. S. (1991) The expression of a deafferentation sundrome in the Sprague-Dowley rat: effects of frontoparietal cortical lesions. Pain 47: 203–209.
Pagni, C. A., Canavero, S. (1995) Functional thalamic depression in a case of reversible central pain due to a spinal intramedullary cyst. Case report. J Neurosurg 83: 163–165.
Palecek, J., Dougherty, P. M., Kim, S. al. (1992) Responses of spinothalamic tract neurons to mechanical and thermal stimuli in an experimental model of peripheral neuropathy in primates. J Neurophysiol 68: 1951–1966.
Palecek, J., Paleckova, V., Dougherty, P. M., Willis, W. D. (1994) The effect of phorbol esters on the responses of primate spinothalamic neurons to mechanical and thermal stimuli. J Neurophysiol 71: 529–537.
Palecek, J., Neugebauer, V., Carlton, S. M., Iyengar, S., Willis, W. D. (2004) The effect of a kainate GluR5 receptor antagonist on responses of spinothalamic tract neurons in a model of peripheral neuropathy in primates. Pain 111: 151–161.
Park, K. M., Max, M. B., Robinovitz, E., Gracely, R. H., Bennett, G. J. (1995) Effects of intravenous ketamine, alfentanil, or placebo on pain, pinprick hyperalgesia, and allodynia produced by intradermal capsaicin in human subjects. Pain 63: 163–172.
Pattany, P. M., Yezierski, R. P., Widerstrom-Noga, E. al. (2002) Proton magnetic resonance spectroscopy of the thalamus in patients with chronic neuropathic pain after spinal cord injury. Am J Neuroradiol 23: 901–905.
Perl, E. R. (1999) Causalgia, pathological pain, and adrenergic receptors. Proc Natl Acad Sci USA 96: 7664–7667.
Petersen, K. L., Fields, H. L., Brennum, J., Sandroni, P., Rowbotham, M. C. (2000) Capsaicin evoked pain and allodynia in post-herpetic neuralgia. Pain 88: 125–133.
Petrovic, P., Ingvar, M., Stone-Elander, S., Petersson, K. M., Hansson, P. (1999) A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy. Pain 83: 459–470.
Peyron, R., Garcia-Larrea, L., Deiber, M. al. (1995) Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study. Pain 62: 275–286.
Peyron, R., Garcia-Larrea, L., Gregoire, M. al. (1998) Allodynia after lateral-medullary (Wallenberg) infart: a PET study. Brain 121: 345–356.
Peyron, R., Garcia-Larrea, L., Gregoire, M. al. (2000) Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case. Pain 84: 77–87.
Peyron, R., Schneider, F., Faillenot, al. (2004) An fMRI study of cortical representation of mechanical allodynia in patients with neuropathic pain. Neurology 63: 1838–1846.
Peyron, R., Faillenot, I., Mertens, P., Laurent, B., Garcia-Larrea, L. (2007) Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study. Neuroimage 34: 310–321.
Radhakrishnan, V., Tsoukatos, J., Davis, K. al. (1999) A comparison of the burst activity of lateral thalamic neurons in chronic pain and non-pain patients. Pain 80: 567–575.
Raichle, M. E., MacLeod, A. M., Snyder, A. al. (2001) A default mode of brain function. Proc Natl Acad Sci USA 98: 676–682.
Rainville, P. (2002) Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol 12: 195–204.
Ralston, D. D., Dougherty, P. M., Lenz, F. al. (2000) Plasticity of the inhibitory circuitry and neuronal responses in the primate somatosensory thalamus following lesions of the dorsal column and spinothalamic pathways. Prog Pain Res Manage 16: 427–434.
Ralston, H. J., Ohara, P. T., Meng, X. W., Wells, J., Ralston, D. D. (1996) Transneuronal changes of the inhibitory circuitry in the macaque somatosensory thalamus following lesions of the dorsal column nuclei. J Comp Neurol 371: 325–335.
Randic, M., Jiang, M. C., Cerne, R. (1993) Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord. J Neurosci 13: 5228–5241.
Rasche, D., Ruppolt, M., Stippich, C., Unterberg, A., Tronnier, V. M. (2006) Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience. Pain 121: 43–52.
Rasmusson, D. D., Louw, D. F., Northgrave, S. A. (1993) The immediate effects of peripheral denervation on inhibitory mechanisms in the somatosensory thalamus. Somatosens Mot Res 10: 69–80.
Rausell, E., Cusick, C. G., Taub, E., Jones, E. G. (1992) Chronic deafferentation in monkeys differentially affects nociceptive and nonnociceptive pathways distinguished by specific calcium-binding proteins and down-regulates gamma-aminobutyric acid type A receptors at thalamic levels. Proc Natl Acad Sci USA 89: 2571–2575.
Ren, K., Dubner, R. (2002) Descending modulation in persistent pain: an update. Pain 100: 1–6.
Riddoch, G. (1938) The clinical features of central pain. Lancet 234: 1093–1209.
Rinaldi, P. C., Young, R. F., Albe-Fessard, D. G., Chodakiewitz, J. (1991) Spontaneous neuronal hyperactivity in the medial and intralaminar thalamic nuclei in patients with deafferentation pain. J Neurosurg 74: 415–421.
Roberts, W. A., Eaton, S. A., Salt, T. E. (1992) Widely distributed GABA-mediated afferent inhibition processes within the ventrobasal thalamus of rat and their possible relevance to pathological pain states and somatotopic plasticity. Exp Brain Res 89: 363–372.
Rowbotham, M. C., Fields, H. L. (1996) The relationship of pain, allodynia and thermal sensation in post-herpetic neuralgia. Brain 119: 347–354.
Rowbotham, M. C., Twilling, L., Davies, P. al. (2003) Oral opioid therapy for chronic peripheral and central neuropathic pain. New Engl J Med 348: 1223–1232.
Salt, T. E. (1989) Gamma-aminobutyric acid and afferent inhibition in the cat and rat ventrobasal thalamus. Neuroscience 28: 17–26.
Sandkuhler, J., Liu, X. (1998) Induction of long-term potentiation at spinal synapses by noxious stimulation or nerve injury. Eur J Neurosci 10: 2476–2480.
Sano, K. (1977) Intralaminar thalamotomy (thalamolaminotomy) and posteromedial hypothalamotomy in the treatment of intractable pain. In Progress in Neurological Surgery (Krayenbuhl, H., Maspes, P. E., Sweet, W. H., eds), pp. 50–103. Basel: Karger.
Sano, K. (1979) Stereotaxic thalamolaminotomy and posteromedial hypothalamotomy for the relief of intractable pain. In Advances in Pain Research and Therapy, Vol. 2 (Bonica, J. J., Ventrafridda, V., eds), pp. 475–485. New York: Raven Press.
Schaible, H. G., Schmidt, R. F. (1985) Effects of an experimental arthritis on the sensory properties of fine articular afferent units. J Neurophysiol 54: 1109–1122.
Schaible, H. G., Schmidt, R. F. (1988) Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis. J Neurophysiol 60: 2180–2195.
Schaible, H. G., Jarrott, B., Hope, P. J., Duggan, A. W. (1990) Release of immunoreactive substance P in the spinal cord during development of acute arthritis in the knee joint of the cat: a study with antibody microprobes. Brain Res 529: 214–223.
Schaible, H. G., Freudenberger, U., Neugebauer, V., Stiller, R. U. (1994) Intraspinal release of immunoreactive calcitonin gene-related peptide during development of inflammation in the joint in vivo – a study with antibody microprobes in cat and rat. Neuroscience 62: 1293–1305.
Schaltenbrand, G., Walker, A. E. (1982) Stereotaxy of the Human Brain. New York: Thieme-Stratton.
Schestatsky, P., Kumru, H., Valls-Sole, al. (2007) Neurophysiologic study of central pain in patients with Parkinson disease. Neurology 69: 2162–2169.
Schilder, P., Stengel, E. (1931) Asymbolia for pain. Arch Neurol Psychiatry 25: 598–600.
Schmahmann, J. D. (2003) Vascular syndromes of the thalamus. Stroke 34: 2264–2278.
Schmahmann, J. D., Leifer, D. (1992) Parietal pseudothalamic pain syndrome. Clinical features and anatomic correlates. Arch Neurol 49: 1032–1037.
Schott, G. D. (1985) Pain in Parkinson's disease. Pain 22: 407–411.
Schurch, B., Wichmann, W., Rossier, A. B. (1996) Post-traumatic syringomyelia (cystic myelopathy): a prospective study of 449 patients with spinal cord injury. J Neurol Neurosurg Psychiatry 60: 61–67.
Seghier, M. L., Lazeyras, F., Vuilleumier, P., Schnider, A., Carota, A. (2005) Functional magnetic resonance imaging and diffusion tensor imaging in a case of central poststroke pain. J Pain 6: 208–212.
Seifert, F., Maihofner, C. (2007) Representation of cold allodynia in the human brain – a functional MRI study. Neuroimage 35: 1168–1180.
Senapati, A. K., Lagraize, S. C., Huntington, P. al. (2005) Electrical stimulation of the anterior cingulate cortex reduces responses of rat dorsal horn neurons to mechanical stimuli. J Neurophysiol 94: 845–851.
Sheth, R. N., Dorsi, M. J., Li, al. (2002) Mechanical hyperalgesia after an L5 ventral rhizotomy or an L5 ganglionectomy in the rat. Pain 96: 63–72.
Shulman, R. G., Rothman, D. L. (1998) Interpreting functional imaging studies in terms of neurotransmitter cycling. Proc Natl Acad Sci USA 95: 11993–11998.
Simone, D. A., Sorkin, L. S., Oh, al. (1991) Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. J Neurophysiol 66: 228–246.
Sluka, K. A., Rees, H., Chen, P. S., Tsuruoka, M., Willis, W. D. (1997) Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate. Exp Brain Res 115: 15–24.
Solaro, C., Brichetto, G., Amato, M. al. (2004) The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study. Neurology 63: 919–921.
Sorkin, L. S., Xiao, W. H., Wagner, R., Myers, R. R. (1997) Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience 81: 255–262.
Starkstein, S. E., Preziosi, T. J., Robinson, R. G. (1991) Sleep disorders, pain, and depression in Parkinson's disease. Eur Neurol 31: 352–355.
Staud, R., Robinson, M. E., Vierck, J., Price, D. D. (2003) Diffuse noxious inhibitory controls (DNIC) attenuate temporal summation of second pain in normal males but not in normal females or fibromyalgia patients. Pain 101: 167–174.
Steriade, M., Deschenes, M. (1984) The thalamus as a neuronal oscillator. Brain Res Rev 8: 1–63.
Steriade, M., Llinas, R. R. (1988) The functional states of the thalamus and the associated neuronal interplay. Physiol Rev 68: 649–742.
Steriade, M., Jones, E. G., Llinas, R. R. (1990) Thalamic Oscillations and Signaling. New York: John Wiley & Sons.
Sun, R. Q., Lawand, N. B., Willis, W. D. (2003) The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of capsaicin. Pain 104: 201–208.
Sun, R. Q., Lawand, N., Lin, Q., Willis, W. D. (2004a) Role of calcitonin gene-related peptide in the sensitization of dorsal horn neurons to mechanical stimulation after intradermal injection of capsaicin. J Neurophysiol 92: 320–326.
Sun, R. Q., Tu, Y., Lawand, N. B., Yan, J. Y., Lin, Q., Willis, W. D. (2004b) Calcitonin gene-related peptide receptor activation produces PKA- and PKC-dependent mechanical hyperalgesia and central sensitization. J Neurophysiol 92: 2859–2866.
Sun, R. Q., Yan, J., Willis, W. D. (2007) Activation of protein kinase B/Akt in the periphery contributes to pain behavior induced by capsaicin in rats. Neurosci 144: 286–294.
Sundgren, P. C., Petrou, M., Harris, R. al. (2007) Diffusion-weighted and diffusion tensor imaging in fibromyalgia patients: a prospective study of whole brain diffusivity, apparent diffusion coefficient, and fraction anisotropy in different regions of the brain and correlation with symptom severity. Acad Radiol 14: 839–846.
Svendsen, F., Tjolsen, A., Gjerstad, J., Hole, K. (1999a) Long term potentiation of single WDR neurons in spinalized rats. Brain Res 816: 487–492.
Svendsen, F., Tjolsen, A., Rygh, L. J., Hole, K. (1999b) Expression of long-term potentiation in single wide dynamic range neurons in the rat is sensitive to blockade of glutamate receptors. Neurosci Lett 259: 25–28.
Sweet, W. H. (1981) Animal models of chronic pain: their possible validation from human experience with posterior rhizotomy and congenital analgesia. Pain 10: 275–295.
Taiwo, Y. O., Heller, P. H., Levine, J. D. (1990) Characterization of distinct phospholipases mediating bradykinin and noradrenaline hyperalgesia. Neuroscience 39: 523–531.
Tal, M., Wall, P. D., Devor, M. (1999) Myelinated afferent fiber types that become spontaneously active and mechanosensitive following nerve transection in the rat. Brain Res 824: 218–223.
Tasker, R. R. (2002) Central pain states. In Bonica's Management of Pain (Loeser, J. D., ed.). New York: Lippincott Williams and Wilkins.
Tasker, R. R., Organ, L. W., Hawrylyshyn, P. (1982) The Thalamus and Midbrain in Man: A Physiologic Atlas using Electrical Stimulation. Springfield: Charles Thomas.
Tasker, R. R., deCarvallo, G., Dostrovsky, J. O. (1991) The history of central pain syndromes, with observations concerning pathophysiology and treatment. In Pain and Central Nervous System Disease: The Central Pain Syndromes (Casey, K. L., ed.), pp. 31–58. New York: Raven Press.
Tasker, R. R., DeCarvalho, G. T., Dolan, E. J. (1992) Intractable pain of spinal cord origin: clinical features and implications for surgery. J Neurosurg 77: 373–378.
Tegeder, I., Costigan, M., Griffin, R. al. (2006) GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 12: 1269–1277.
Torebjörk, H. E., Lundberg, L. E. R., LaMotte, R. G. (1992) Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol 448: 765–780.
Triggs, W. J., Beric, A. (1994) Dysaesthesiae induced by physiological and electrical activation of posterior column afferents after stroke. J Neurol Neurosurg Psychiatry 57: 1077–1080.
Urabe, M., Tsubokawa, T. (1965) Stereotaxic thalamotomy for the relief of intractable Tohoku pain. J Exp Med 85: 286–298.
Buren, J. M., Borke, R. C. (1972) Variations and Connections of the Human Thalamus. Berlin: Springer Verlag.
Pol, A. N., Obrietan, K., Chen, G. (1996) Excitatory actions of GABA after neuronal trauma. J Neurosci 16: 4283–4292.
Hoesen, G. W., Morecraft, R. J., Vogt, B. A. (1993) Connections of the monkey cingulate cortex. In Neurobiology of Cingulate Cortex and Limbic Thalamus: A Comphrehensive Handbook (Vogt, B. A., Gabriel, M., eds), pp. 249–284. Boston: Birkhäuser.
Verdugo, R. J., Campero, M., Ochoa, J. L. (1994) Phentolamine sympathetic block in painful polyneuropathies. II. Further questioning of the concept of “sympathetically maintained pain”. Neurology 44: 1010–1014.
Vestergaard, K., Nielsen, J., Andersen, al. (1995) Sensory abnormalities in consecutive unselected patients with central post-stroke pain. Pain 61: 177–186.
Vierck, C. J. (1991) Can mechanisms of central pain syndromes be investigated in animal models? In Pain and Central Nervous System Disease: The Central Pain Syndromes (Casey, K. L., ed.), pp. 129–141. New York: Raven Press.
Vierck, C. J., Luck, M. M. (1979) Loss and recovery of reactivity to noxious stimuli in monkeys with primary spinothalamic cordotomies, followed by secondary and tertiary lesions of other cord sectors. Brain 102: 233–248.
Vierck, C. J., Lineberry, C. G., Lee, P. K., Calderwood, H. W. (1974) Prolonged hypalgesia following “acupuncture” in monkeys. Life Sci 15: 1277–1289.
Vierck, C. J., Greenspan, J. D., Ritz, L. A. (1990) Long-term changes in purposive and reflexive responses to nociceptive stimulation following anterolateral chordotomy. J Neurosci 10: 2077–2095.
Villanueva, L., Nathan, P. W. (2000) Multiple pain pathways. In Proceedings of the 9th World Congress on Pain (Devor, M., Rowbotham, M., Wiesenfeld-Hallin, Z., eds), pp. 371–386. Seattle: IASP Press.
Vogt, B. A. (2005) Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci 6: 533–544.
Wagner, R., Janjigian, M., Myers, R. R. (1998) Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression. Pain 74: 35–42.
Waxman, S. G. (2001) Acquired channelopathies in nerve injury and MS. Neurology 56: 1621–1627.
Waxman, S. G. (2007) Nav1.7, its mutations, and the syndromes that they cause. Neurology 69: 505–507.
Waxman, S. G., Hains, B. C. (2006) Fire and phantoms after spinal cord injury: Na+ channels and central pain. Trends Neurosci 29: 207–215.
Waxman, S. G., Dib-Hajj, S., Cummins, T. R., Black, J. A. (1999) Sodium channels and pain. Proc Natl Acad Sci USA 96: 7635–7639.
Weng, H. R., Lee, J.-I., Lenz, F. al. (2000) Functional plasticity in primate somatosensory thalamus following chronic lesion of the ventral lateral spinal cord. Neuroscience 101: 393–401.
Westlund, K. N., Carlton, S. M., Zhang, D., Willis, W. D. (1992) Glutamate-immunoreactive terminals synapse on primate spinothalamic tract cells. J Comp Neurol 322: 519–527.
Wilkins, R. H., and Brody, I. A. (1970) Causalgia (Weir Mitchell) Neurological classics XXVII. Arch Neurol 22: 89–94.
Williams, D. A., Gracely, R. H. (2006) Functional magnetic resonance imaging findings in fibromyalgia. Arthritis Res Ther 8: 224–232.
Willis, W. D. (1985) The Pain System. Basel: Karger.
Willis, W. D. (1999) Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp Brain Res 124: 395–421.
Willis, W. D. (2002) Long-term potentiation in spinothalamic neurons. Brain Res Rev 40: 202–214.
Willis, W. D., Coggeshall, R. E. (1991) Sensory Mechanisms of the Spinal Cord. New York: Plenum Press.
Willis, W. D., Coggeshall, R. E. (2004) Sensory Mechanisms of the Spinal Cord. New York: Plenum Press.
Willoch, F., Tolle, T. R., Wester, H. al. (1999) Central pain after pontine infarction is associated with changes in opioid receptor binding: a PET study with 11C-diprenorphine. Am J Neuroradiol 20: 686–690.
Willoch, F., Schindler, F., Wester, H. al. (2004) Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [11C]diprenorphine PET study. Pain 108: 213–220.
Wilson, J. A., Nimmo, A. F., Fleetwood-Walker, S. M., Colvin, L. A. (2008) A randomised double blind trial of the effect of pre-emptive epidural ketamine on persistent pain after lower limb amputation. Pain 135: 108–118.
Witting, N., Kupers, R. C., Svensson, al. (2001) Experimental brush-evoked allodynia activates posterior parietal cortex. Neurology 57: 1817–1824.
Wu, G., Ringkamp, M., Hartke, T. al. (2001) Early onset of spontaneous activity in uninjured C-fiber nociceptors after injury to neighboring nerve fibers. J Neurosci 21: 140RC.
Wu, G., Ringkamp, M., Murinson, B. al. (2002) Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents. J Neurosci 22: 7746–7753.
Wu, J., Fang, L., Lin, Q., Willis, W. D. (2002) The role of nitric oxide in the phosphorylation of cyclic adenosine monophosphate-responsive element-binding protein in the spinal cord after intradermal injection of capsaicin. J Pain 3: 190–198.
Xu, J., Wall, J. T. (1997) Rapid changes in brainstem maps of adult primates after peripheral injury. Brain Res 774: 211–215.
Yaksh, T. L., Hua, X. Y., Kalcheva, I., Nozaki-Taguchi, N., Marsala, M. (1999) The spinal biology in humans and animals of pain states generated by persistent small afferent input. Proc Natl Acad Sci USA 96: 7680–7686.
Yezierski, R. P., Park, S. H. (1993) The mechanosensitivity of spinal sensory neurons following intraspinal injections of quisqualic acid in the rat. Neurosci Lett 157: 115–119.
Yezierski, R. P., Gerhart, K. D., Schrock, B. J., Willis, W. D. (1983) A further examination of effects of cortical stimulation on primate spinothalamic tract cells. J Neurophysiol 49: 424–441.
Yezierski, R. P., Santana, M., Park, S. H., Madsen, P. W. (1993) Neuronal degeneration and spinal cavitation following intraspinal injections of quisqualic acid in the rat. J Neurotrauma 10: 445–456.
Zirh, A. T., Lenz, F. A., Reich, S. G., Dougherty, P. M. (1997) Patterns of bursting occurring in thalamic cells during Parkinsonian tremor. Neuroscience 83: 107–121.
Zhang, X., Wu, J., Fang, L., Willis, W. D. (2003) The effects of protein phosphatase inhibitors on nociceptive behavioral responses of rats following intradermal injection of capsaicin. Pain 106: 443–451.
Zhang, X., Wu, J., Lei, Y., Fang, L., Willis, W. D. (2005) Protein phosphatase modulates the phosphorylation of spinal cord NMDA receptors in rats following intradermal injection of capsaicin. Brain Res Mol Brain Res 138: 264–272.
Zou, X., Lin, Q., Willis, W. D. (2000) Enhanced phosphorylation of NMDA receptor 1 subunits in spinal cord dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats. J Neurosci 20: 6989–6997.
Zou, X., Lin, Q., Willis, W. D. (2002) Role of protein kinase A in phosphorylation of NMDA receptor 1 subunits in dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats. Neuroscience 115: 775–786.
Zubieta, J. K., Smith, Y. R., Bueller, J. al. (2001) Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science 293: 311–315.