Pain mechanisms: labeled lines versus convergence in central processing.

The issue of whether pain is represented by specific neural elements or by patterned activity within a convergent somatosensory subsystem has been debated for over a century. The gate control theory introduced in 1965 denied central specificity, and since then most authors have endorsed convergent wide-dynamic-range neurons. Recent functional and anatomical findings provide compelling support for a new perspective that views pain in humans as a homeostatic emotion that integrates both specific labeled lines and convergent somatic activity.

[1]  R. Schmidt,et al.  Convergence of muscle and cutaneous input onto primate spinothalamic tract neurons , 1977, Brain Research.

[2]  A. Craig,et al.  Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch , 2001, Nature Neuroscience.

[3]  A. Levinsson Spinal Cord Processing of Sensory Information: Spatial Organization and Adaptive Mechanisms. , 2000 .

[4]  J. Kaas The functional organization of somatosensory cortex in primates. , 1993, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[5]  R. Hari,et al.  Altered central sensorimotor processing in patients with complex regional pain syndrome , 2002, Pain.

[6]  T. Ness,et al.  Central mechanisms of visceral pain. , 1991, Canadian journal of physiology and pharmacology.

[7]  H. Burton,et al.  The posterior thalamic region and its cortical projection in new world and old world monkeys , 1976, The Journal of comparative neurology.

[8]  J. Donoghue,et al.  Plasticity and primary motor cortex. , 2000, Annual review of neuroscience.

[9]  Fred A Lenz,et al.  Pain sensitivity alterations as a function of lesion location in the parasylvian cortex , 1999, Pain.

[10]  R. Dubner,et al.  Neurons that subserve the sensory-discriminative aspects of pain , 1977, Pain.

[11]  J. Dostrovsky,et al.  Thalamic relay site for cold perception in humans. , 1999, Journal of neurophysiology.

[12]  A. Ptito,et al.  Central pain in a hemispherectomized patient , 2001, European journal of pain.

[13]  R. Hassler,et al.  [Clinical and anatomical findings in stereotactic pain operations on the thalamus]. , 1959, Archiv fur Psychiatrie und Nervenkrankheiten, vereinigt mit Zeitschrift fur die gesamte Neurologie und Psychiatrie.

[14]  S Mense,et al.  Different types of slowly conducting afferent units in cat skeletal muscle and tendon. , 1985, The Journal of physiology.

[15]  A Schnitzler,et al.  Pain affect without pain sensation in a patient with a postcentral lesion , 1999, Pain.

[16]  A. Craig,et al.  Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus. , 2000, Brain : a journal of neurology.

[17]  S. Ranson CUTANEOUS SENSATION. , 2022, Science.

[18]  J. Dostrovsky,et al.  Pain-related neurons in the human cingulate cortex , 1999, Nature Neuroscience.

[19]  M. Bushnell,et al.  Cortical representation of the sensory dimension of pain. , 2001, Journal of neurophysiology.

[20]  G. Holmes,et al.  Sensory disturbances from cerebral lesions , 1911 .

[21]  T. Insel,et al.  Autoradiographic and in situ hybridization localization of corticotropin‐releasing factor 1 and 2 receptors in nonhuman primate brain , 1999, The Journal of comparative neurology.

[22]  A. K. Jones,et al.  Cerebral responses to a continual tonic pain stimulus measured using positron emission tomography , 1998, Pain.

[23]  J. Schmahmann,et al.  Parietal pseudothalamic pain syndrome. Clinical features and anatomic correlates. , 1992, Archives of neurology.

[24]  R. Meyer,et al.  Response of cutaneous A- and C-fiber nociceptors in the monkey to controlled-force stimuli. , 2000, Journal of neurophysiology.

[25]  B L Whitsel,et al.  Anterior parietal cortical response to tactile and skin-heating stimuli applied to the same skin site. , 1996, Journal of neurophysiology.

[26]  P. Wall,et al.  Pain mechanisms: a new theory. , 1965, Science.

[27]  W. Willis,et al.  Responses of primate spinothalamic neurons located in the sacral intermediomedial gray (stilling's nucleus) to proprioceptive input from the tail , 1982, Brain Research.

[28]  M. Rosas-Arellano,et al.  c-Fos induction in spinal cord neurons after renal arterial or venous occlusion. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[29]  W. Willis,et al.  Projections from the marginal zone and deep dorsal horn to the ventrobasal nuclei of the primate thalamus , 2001, Pain.

[30]  Y. Lamarre,et al.  Unmyelinated tactile afferents signal touch and project to insular cortex , 2002, Nature Neuroscience.

[31]  A. Craig The functional anatomy of lamina I and its role in post-stroke central pain. , 2000, Progress in brain research.

[32]  E. Perl,et al.  Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. , 1970, Journal of neurophysiology.

[33]  P. Mantyh,et al.  Spinal Neurons that Possess the Substance P Receptor Are Required for the Development of Central Sensitization , 2002, The Journal of Neuroscience.

[34]  Arthur G. Bills,et al.  Sensation and perception in the history of experimental psychology. , 1943 .

[35]  M Ingvar,et al.  A PET activation study of dynamic mechanical allodynia in patients with mononeuropathy , 1999, PAIN®.

[36]  W. Miltner,et al.  Dipole analysis of ultralate (C-fibres) evoked potentials after laser stimulation of tiny cutaneous surface areas in humans , 2001, Neuroscience Letters.

[37]  P. Scheiffele Cell-cell signaling during synapse formation in the CNS. , 2003, Annual review of neuroscience.

[38]  R. Joynt Descartes' Error: Emotion, Reason, and the Human Brain , 1995 .

[39]  M. Bushnell,et al.  A thalamic nucleus specific for pain and temperature sensation , 1994, Nature.

[40]  L. Swanson Cerebral hemisphere regulation of motivated behavior 1 1 Published on the World Wide Web on 2 November 2000. , 2000, Brain Research.

[41]  F. Mauguière,et al.  Representation of pain and somatic sensation in the human insula: a study of responses to direct electrical cortical stimulation. , 2002, Cerebral cortex.

[42]  J. Ochoa,et al.  Identification of muscle afferents subserving sensation of deep pain in humans. , 1994, Journal of neurophysiology.

[43]  E. Boring Sensation and Perception. (Scientific Books: Sensation and Perception in the History of Experimental Psychology) , 1943 .

[44]  M. Bushnell,et al.  Responses of monkey medullary dorsal horn neurons during the detection of noxious heat stimuli. , 1989, Journal of neurophysiology.

[45]  B L Whitsel,et al.  Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode. , 1997, Journal of neurophysiology.

[46]  E. Torebjörk Subpopulations of human C nociceptors and their sensory correlates. , 2000 .

[47]  A. Craig,et al.  Is there a specific lamina I spinothalamocortical pathway for pain and temperature sensations in primates? , 2002, The journal of pain : official journal of the American Pain Society.

[48]  R. Schmidt,et al.  Somatosympathetic reflexes: afferent fibers, central pathways, discharge characteristics. , 1973, Physiological reviews.

[49]  C. Vierck,et al.  Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome , 2001, Pain.

[50]  R Dubner,et al.  Activity of trigeminothalamic neurons in medullary dorsal horn of awake monkeys trained in a thermal discrimination task. , 1984, Journal of neurophysiology.

[51]  J. Voogd,et al.  Propriospinal neurons with ascending collaterals to the dorsal medulla, the thalamus and the tectum: a retrograde fluorescent double-labeling study of the cervical cord of the rat , 2004, Experimental Brain Research.

[52]  E. G. Jones,et al.  Calbindin and parvalbumin cells in monkey VPL thalamic nucleus: distribution, laminar cortical projections, and relations to spinothalamic terminations , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[53]  A. Lundberg,et al.  Reflex pathways from group II muscle afferents , 2004, Experimental Brain Research.

[54]  F. Mauguière,et al.  Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case , 2000, Pain.

[55]  P. Petrovic,et al.  Placebo and Opioid Analgesia-- Imaging a Shared Neuronal Network , 2002, Science.

[56]  H. Freund,et al.  Differential organization of touch and pain in human primary somatosensory cortex. , 2000, Journal of neurophysiology.

[57]  H. Burton,et al.  Somatic submodality distribution within the second somatosensory (SII), 7b, retroinsular, postauditory, and granular insular cortical areas of M. fascicularis , 1980, The Journal of comparative neurology.

[58]  C. Beverley,et al.  The effect of methadone and naloxone on cultured rat liver cells. , 1984, Experimental cell biology.

[59]  P. Wilson Psychological and Neural Mechanisms of Pain , 1988 .

[60]  Patrick D. Wall,et al.  Dorsal Horn Electrophysiology , 1973 .

[61]  Walter Magerl,et al.  Spatial discrimination thresholds for pain and touch in human hairy skin , 2001, Pain.

[62]  M. Wiesmann,et al.  Cerebral functional magnetic resonance imaging of vestibular, auditory, and nociceptive areas during galvanic stimulation , 1998, Annals of neurology.

[63]  Bruce Pike,et al.  Differentiating noxious- and innocuous-related activation of human somatosensory cortices using temporal analysis of fMRI. , 2002, Journal of neurophysiology.

[64]  A. Craig How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[65]  E. Carstens Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of histamine, capsaicin, and other irritants. , 1997, Journal of neurophysiology.

[66]  L. Kempe Handbook of Physiology. Section I. The Nervous System , 1982 .

[67]  H. Koerber,et al.  Central anatomy of individual rapidly adapting low‐threshold mechanoreceptors innervating the “hairy” skin of newborn mice: Early maturation of hair follicle afferents , 2001, The Journal of comparative neurology.

[68]  J. Gybels,et al.  Positron emission tomography study of a chronic pain patient successfully treated with somatosensory thalamic stimulation , 2000, Pain.

[69]  J. Schouenborg,et al.  A survey of spinal dorsal horn neurones encoding the spatial organization of withdrawal reflexes in the rat , 2004, Experimental Brain Research.

[70]  J. Altman,et al.  The development of the rat spinal cord. , 1984, Advances in anatomy, embryology, and cell biology.

[71]  Donald D. Price,et al.  The roles of spatial recruitment and discharge frequency in spinal cord coding of pain: a combined electrophysiological and imaging investigation , 1993, Pain.

[72]  A. Craig,et al.  Behavioral thermosensitivity after lesions of thalamic target areas of a thermosensory spinothalamic pathway in the cat. , 1999, Journal of neurophysiology.

[73]  E. Perl Why are Selectively Responsive and Multireceptive Neurons both Present in Somatosensory Pathways , 1984 .

[74]  Xiao Hong Yu,et al.  NK-1 Receptor Immunoreactivity in Distinct Morphological Types of Lamina I Neurons of the Primate Spinal Cord , 1999, The Journal of Neuroscience.

[75]  R. Foreman Mechanisms of cardiac pain. , 1999, Annual review of physiology.

[76]  Ralph Norgren,et al.  The nucleus of the solitary tract in the monkey: Projections to the thalamus and brain stem nuclei , 1980, The Journal of comparative neurology.

[77]  J. Prechtl,et al.  B-Afferents: A fundamental division of the nervous system mediating homeostasis? , 1990, Behavioral and Brain Sciences.

[78]  J. Gybels,et al.  A comparison between the discharges of human nociceptive nerve fibres and the subject's ratings of his sensations. , 1979 .

[79]  A. Craig,et al.  Responses of spinothalamic lamina I neurons to repeated brief contact heat stimulation in the cat. , 2002, Journal of neurophysiology.

[80]  W. Cannon The Wisdom of the Body , 1932 .

[81]  H. Fields,et al.  The affective component of pain in rodents: Direct evidence for a contribution of the anterior cingulate cortex , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[82]  M. Bushnell,et al.  Pain perception: is there a role for primary somatosensory cortex? , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[83]  J. Hoover,et al.  Retrograde labeling of lumbosacral interneurons following injections of red and green fluorescent microspheres into hindlimb motor nuclei of the cat. , 1992, Somatosensory & motor research.

[84]  R. LaMotte,et al.  Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. , 1991, Journal of neurophysiology.

[85]  R. Rey The History of Pain , 1995, Nature Medicine.

[86]  W. Willis,et al.  Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons. , 1999, Journal of neurophysiology.

[87]  L. Krubitzer,et al.  Somatotopic organization of cortical fields in the lateral sulcus of Homo sapiens: Evidence for SII and PV , 2000, The Journal of comparative neurology.

[88]  E. Reiman,et al.  Thermosensory activation of insular cortex , 2000, Nature Neuroscience.

[89]  D. Price,et al.  Neurophysiological characterization of the anterolateral spinal cord neurons contributing to pain perception in man , 1975, Pain.

[90]  H. Handwerker,et al.  Prolonged noxious mechanical stimulation of the rat's tail: responses and encoding properties of dorsal horn neurones. , 1988, The Journal of physiology.

[91]  P. Wall,et al.  Slow changes in the flexion reflex of the rat following arthritis or tenotomy , 1988, Brain Research.

[92]  Wilfrid Jänig,et al.  Visceral nociceptors: a new world order? , 1992, Trends in Neurosciences.

[93]  Alan C. Evans,et al.  Functional imaging of an illusion of pain , 1996, Nature.

[94]  Central Pain: A Neurosurgical Challenge , 1999 .

[95]  Krish D. Singh,et al.  fMRI of Thermal Pain: Effects of Stimulus Laterality and Attention , 2002, NeuroImage.

[96]  J. Dostrovsky,et al.  Role of thalamus in pain. , 2000, Progress in brain research.

[97]  G. Mower Perceived intensity of peripheral thermal stimuli is independent of internal body temperature. , 1976, Journal of comparative and physiological psychology.

[98]  J D Greenspan,et al.  Peripheral coding of tonic mechanical cutaneous pain: comparison of nociceptor activity in rat and human psychophysics. , 1999, Journal of neurophysiology.

[99]  A. Craig,et al.  Activation of spinobulbar lamina I neurons by static muscle contraction. , 2002, Journal of neurophysiology.

[100]  R. Hassler,et al.  Klinische und anatomische Befunde bei stereotaktischen Schmerzoperationen im Thalamus , 2004, Archiv für Psychiatrie und Nervenkrankheiten.

[101]  Stanley Finger,et al.  Cutaneous sensory spots and the “law of specific nerve energies”: history and development of ideas , 1999, Brain Research Bulletin.

[102]  R. Schmidt Presynaptic inhibition in the vertebrate central nervous system. , 1971, Ergebnisse der Physiologie, biologischen Chemie und experimentellen Pharmakologie.

[103]  W. Willis,et al.  Natural groupings of primate spinothalamic neurons based on cutaneous stimulation. Physiological and anatomical features. , 1988, Journal of neurophysiology.

[104]  M. Bushnell,et al.  Pain affect encoded in human anterior cingulate but not somatosensory cortex. , 1997, Science.

[105]  A. Craig,et al.  Responses of spinothalamic lamina I neurons to maintained noxious mechanical stimulation in the cat. , 2002, Journal of neurophysiology.

[106]  Gordon M Shepherd,et al.  Multiple modes of action potential initiation and propagation in mitral cell primary dendrite. , 2002, Journal of neurophysiology.

[107]  C. Adreani,et al.  Effect of arterial occlusion on responses of group III and IV afferents to dynamic exercise. , 1998, Journal of applied physiology.

[108]  R. Meyer,et al.  Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. , 1999, Brain : a journal of neurology.

[109]  K. Zilles,et al.  Hierarchical Processing of Tactile Shape in the Human Brain , 2001, Neuron.

[110]  A. Craig,et al.  Nociceptive and thermoreceptive lamina I neurons are anatomically distinct , 1998, Nature Neuroscience.

[111]  W. Willis,et al.  Neuroanatomy of the pain system and of the pathways that modulate pain. , 1997, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[112]  F. Mauguière,et al.  Flexion reflexes following anterolateral cordotomy in man: dissociation between pain sensation and nociceptive reflex RIII , 1993, Pain.

[113]  N Birbaumer,et al.  Reorganization of Motor and Somatosensory Cortex in Upper Extremity Amputees with Phantom Limb Pain , 2001, The Journal of Neuroscience.

[114]  R. Coghill,et al.  Wide dynamic range but not nociceptive-specific neurons encode multidimensional features of prolonged repetitive heat pain. , 1993, Journal of neurophysiology.

[115]  R. Edward Pain and the discovery of nociceptors , 1996 .

[116]  W. Willis,et al.  Responses of spinothalamic tract cells in the superficial dorsal horn of the primate lumbar spinal cord. , 1987, The Journal of physiology.

[117]  A. Craig,et al.  Is neuropathic pain caused by the activation of nociceptive‐specific neurons due to anatomic sprouting in the dorsal horn? , 2000, The Journal of comparative neurology.

[118]  A. Damasio Descartes' error: emotion, reason, and the human brain. avon books , 1994 .

[119]  A. Craig,et al.  Association of spinothalamic lamina I neurons and their ascending axons with calbindin-immunoreactivity in monkey and human , 2002, Pain.

[120]  L. Wilson,et al.  Neuronal application of capsaicin modulates somatic pressor reflexes. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[121]  A. Craig,et al.  Quantitative response characteristics of thermoreceptive and nociceptive lamina I spinothalamic neurons in the cat. , 2001, Journal of neurophysiology.

[122]  A. Apkarian,et al.  Cortical representation of pain: functional characterization of nociceptive areas near the lateral sulcus , 2000, Pain.