Studies of the organization of the human nociceptive withdrawal reflex: Focus on sensory convergence and stimulation site dependency

Acta Physiologica

Volumn 189, Issue SUPPL. 654, 2007, Pages 1-35

  Andersen, O K ^a  

^a AALBORG UNIVERSITY   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; ANALGESIC AGENT; CAPSAICIN; CLONIDINE; KETAMINE; LEVODOPA; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NALOXONE;

ELECTROSTIMULATION; EXPERIMENTAL STUDY; FLEXOR REFLEX; HUMAN; MEDICAL RESEARCH; NERVE CONDUCTION; NEUROMUSCULAR SYNAPSE; NOCICEPTIVE RECEPTOR; NOCICEPTIVE STIMULATION; NONHUMAN; PAIN; PAIN ASSESSMENT; PHYSIOLOGY; PRIORITY JOURNAL; RECEPTIVE FIELD; REVIEW; SENSITIZATION; SENSORY NERVE; SENSORY STIMULATION; SPATIAL SUMMATION; SPINAL REFLEX; TEMPORAL SUMMATION; WITHDRAWAL REFLEX;

ANIMALS; ELECTRIC STIMULATION; FOOT; HUMANS; MODELS, NEUROLOGICAL; NEURAL PATHWAYS; NEURONS, AFFERENT; PAIN; PAIN MEASUREMENT; PSYCHOMOTOR PERFORMANCE; REACTION TIME; REFLEX; SKIN; SPINAL CORD;

EID: 34247229227     PISSN: 17481708     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1748-1716.2007.01706.x     Document Type: Review

References (214)

1. Adriaensen, H., Gybels, J., Handwerker, H.O. & Hees, J.V. 1983. Responses properties of thin myelinated (Aδ) fibers in human skin nerves. J Neurophysiol 49, 111-122.
2. Adriaensen, H., Gybels, J., Handwerker, H.O. & Van Hees, J. 1984. Nociceptor discharges and sensations due to prolonged noxious mechanical stimulation - a paradox. Hum Neurobiol 3, 53-58.
3. Anden, N.E., Jukes, M.G.M. & Lundberg, A. 1964a. Spinal reflexes and monoamine liberation. Nature 202, 1222-1223.
4. Anden, N.E., Jukes, M.G.M., Lundberg, A. & Vyklicky, L. 1964b. A new spinal flexor reflex. Nature 202, 1344-1345.
5. Anden, N.E., Jukes, M.G., Lundberg, A. & Vyklicky, L. 1966. The effect of DOPA on the spinal cord. 1. Influence on transmission from primary afferents. Acta Physiol Scand 67, 373-386.
6. Andersen, O.K., Jensen, L.M., Brennum, J. & Arendt-Nielsen, L. 1995. Modulation of the human nociceptive reflex by cyclic movements. Eur J Appl Physiol 70, 311-321.
7. Andersen, O.K., Felsby, S., Nikolajsen, L. et al. 1996. The effect of ketamine on stimulation of primary and secondary hyperalgesic areas induced by capsaicin - a double-blind, placebo-controlled, human experimental study. Pain 66, 51-62.
8. Andersen, O.K., Svensson, P., Ellrich, J. & Arendt-Nielsen, L. 1998. Conditioning of the masseter inhibitory reflex by homotopically applied painful heat in humans. Electroencephalogr Clin Neurophysiol 109, 508-514.
9. Andersen, O.K., Eichenberger, U. & Arendt-Nielsen, L. 2002. Reflex receptive field size variation following intramuscular capsaicin injection in humans. Abstracts - Xth World Congress on Pain, p. 517.
10. Andersen, O.K., Mørch, C.D. & Arendt-Nielsen, L. 2006. Modulation of heat evoked nociceptive withdrawal reflexes by painful intramuscular conditioning stimulation. Exp Brain Res 174, 775-780.
11. Arendt-Nielsen, L., Brennum, J., Sindrup, S. & Bak, P. 1994. Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system. Eur J Appl Physiol 68, 266-273.
12. Arendt-Nielsen, L., Petersen-Felix, S., Fischer, M. et al. 1995. The effect of N-methyl-D-aspartate antagonist (Ketamine) on single and repeated nociceptive stimuli: a placebo-controlled experimental human study. Anesth Analg 81, 63-68.
13. Arendt-Nielsen, L., Andersen, O.K. & Jensen, T.S. 1996. Brief, prolonged, and repeated stimuli applied to hyperalgesic skin areas: a psychophysical study. Brain Res 712, 165-167.
14. Bajaj, P., Arendt-Nielsen, L. & Andersen, O.K. 2005. Facilitation and inhibition of withdrawal reflexes following repetitive stimulation: electro- and psychophysiological evidence for activation of noxious inhibitory controls in humans. Eur J Pain 9, 25-31.
15. Baken, B.C., Nieuwenhuijzen, P.H., Bastiaanse, C.M., Dietz, V. & Duysens, J. 2006. Cutaneous reflexes evoked during human walking are reduced when self-induced. J Physiol 570, 113-124.
16. Baldissera, F., Hultborn, H. & Illert, M. 1981. Integration in spinal neuronal systems. In: V.B. Brooks (ed.) Handbook of Physiology. Vol. 2, Sect I, Nervous System, Motor Control, Part 1, pp. 509-595. American Physiological Society, Bethesda, MD.
17. Bastiaanse, C.M., Duysens, J. & Dietz, V. 2000. Modulation of cutaneous reflexes by load receptor input during human walking. Exp Brain Res 135, 189-198.
18. Bathien, N. 1971. Reflexes spinaux chez l'homme et niveaux d'attention. Electroencephalogr Clin Neurophysiol 30, 32-37.
19. Baxendale, R.H. & Ferrel, W.R. 1980. Modulation of transmission in flexion reflex pathways by knee joint afferent discharge in the decerebrate cat. Brain Res 202, 497-500.
20. Beggs, S., Torsney, C., Drew, L.J. & Fitzgerald, M. 2002. The postnatal reorganization of primary afferent input and dorsal horn cell receptive fields in the rat spinal cord is an activity-dependent process. Eur J Neurosci 16, 1249-1258.
21. Behrends, T., Schomburg, E.D. & Steffens, H. 1983. Facilitatory interaction between cutaneous afferents from low threshold mechanoreceptors and nociceptors in segmental reflex pathways to α-motorneurons. Brain Res, 260, 131-134.
22. Belanger, M. & Patla, A.E. 1984. Corrective responses to perturbation applied during walking in humans. Neurosci Lett 49, 291-295.
23. Belanger, M. & Patla, A.E. 1987. Phase-dependent compensatory responses to perturbation applied during walking in humans. J Mot Behav 19, 434-453.
24. Bent, L.R., Potvin, J.R., Brooke, J.D. & McIlroy, W.E. 2001. Medio-lateral balance adjustments preceding reflexive limb withdrawal are modified by postural demands. Brain Res 914, 100-105.
25. Bergadano, A., Andersen, O.K., Arendt-Nielsen, L., Schatzmann, U. & Spadavecchia, C. 2006. Quantitative assessment of nociceptive processes in conscious dogs by use of the nociceptive withdrawal reflex. Am J Vet Res 67, 882-889.
26. Borszcz, G.S., Johnson, C.P., Anderson, M.E. & Young, B.J. 1992. Characterization of tailshock elicited withdrawal reflexes in intact and spinal rats. Physiol Behav 52, 1055-1062.
27. Bouhassira, D., Chollet, R., Coffin, B. et al. 1994. Inhibition of a somatic nociceptive reflex by gastric distension in humans. Gastroenterology 107, 985-992.
28. Bouhassira, D., Sabate, J.M., Coffin, B. et al. 1998. Effects of rectal distensions on nociceptive flexion reflexes in humans. Am J Physiol 275, G410-G417.
29. 2 laser stimulation. Hum Neurobiol 3, 33-40.
30. Brown, D.A. & Kukulka, C.G. 1993. Human flexor reflex modulation during cycling. J Neurophysiol 69, 1212-1224.
31. Burgess, P.R. & Perl, E.R. 1973. Cutaneous mechanoreceptors and nociceptors. In: A. Iggo (ed.) Handbook of Physiology II. Somatosensory System, pp. 29-78. Springer-Verlag, Berlin.
32. Burke, D., Mackenzie, R.A., Skuse, N.F. & Lethlean, A.K. 1975. Cutaneous afferent activity in median and radial nerve fascicles: a microelectrode study. J Neurol Neurosurg Psychiatry 38, 855-864.
33. Bussel, B., Roby-Brami, A., Yakovleff, A. & Bennis, N. 1989. Late flexion reflex in paraplegic patients. Evidence for a spinal stepping generator. Brain Res Bull 22, 53-56.
34. Cain, D.M., Khasabov, S.G. & Simone, D.A. 2001. Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study. J Neurophysiol 85, 1561-1574.
35. Campbell, I.G., Carstens, E. & Watkins, L.R. 1991. Comparisons of human pain sensation and flexion withdrawal evoked by noxious radiant heat. Pain 45, 259-268.
36. Carstens, E. & Campbell, I.G. 1992. Responses of motor units during the hind limb flexion withdrawal reflex evoked by noxious skin heating: phasic and prolonged suppression by midbrain stimulation and comparison with simultaneously recorded dorsal horn units. Pain 48, 215-226.
37. Carstens, E., Hartung, M., Stelzer, B. & Zimmermann, M. 1990. Suppression of a hind limb flexion withdrawal reflex by microinjection of glutamate or morphine into the periaqueductal gray in the rat. Pain 43, 105-112.
38. Chan, C.W.Y. & Dallaire, M. 1989. Subjective pain sensation is linearly correlated with the flexion reflex in man. Brain Res 479, 145-150.
39. Chan, C.W.Y. & Tsang, H.H.Y. 1985. A quantitative study of flexion reflex in man: relevance to pain research. In: H.L. Fields, R. Dubner & F. Cervero (eds) Advances in Pain Research and Therapy, pp. 361-370. Raven Press, New York.
40. Chung, J.M., Fang, Z.R., Cargill, C.L. & Willis, W.D. 1983. Prolonged, naloxone-reversible inhibition of the flexion reflex in the cat. Pain 15, 35-53.
41. Clarke, R.W. & Harris, J. 2001. The spatial organization of central sensitization of hind limb flexor reflexes in the decerebrated, spinalized rabbit. Eur J Pain 5, 175-185.
42. Clarke, R.W. & Harris, J. 2004. The organization of motor responses to noxious stimuli. Brain Res Brain Res Rev 46, 163-172.
43. Clarke, R.W., Ford, T.W. & Taylor, J.S. 1988. Adrenergic and opioidergic modulation of a spinal reflex in the decerebrated rabbit. J Physiol 404, 407-417.
44. Clarke, R.W., Ford, T.W. & Taylor, J.S. 1989a. Activation by high intensity peripheral nerve stimulation of adrenergic and opioidergic inhibition of a spinal reflex in the decerebrated rabbit. Brain Res 505, 1-6.
45. Clarke, R.W., Ford, T.W. & Taylor, J.S. 1989b. Reflex actions of selective stimulation of sural nerve C fibres in the rabbit. Q J Exp Physiol 74, 681-690.
46. Clarke, R.W., Harris, J., Ford, T.W. & Taylor, J.S. 1992. Prolonged potentiation of transmission through a withdrawal reflex pathway after noxious stimulation of the heel in the rabbit. Pain 49, 65-70.
47. Clarke, R.W., Wych, B.E. & Harris, J. 2001. Adaptive changes in withdrawal reflexes after noxious stimulation at the heel and the toes in the decerebrated rabbit. Neurosci Lett 304, 120-122.
48. Clarke, R.W., Eves, S., Harris, J., Peachey, J.E. & Stuart, E. 2002. Interactions between cutaneous afferent inputs to a withdrawal reflex in the decerebrated rabbit and their control by descending and segmental systems. Neuroscience 112, 555-571.
49. Clarke, R.W., Brown-Reid, K., Kasher, P. & Harris, J. 2003. Tetrodotoxin block of A-fibre conduction and its effect on reflex responses evoked by electrical stimulation of the sural nerve in the decerebrated rabbit. Exp Physiol 88, 13-18.
50. Cleland, C.L. & Bauer, R.E. 2002. Spatial transformations in the withdrawal response of the tail in intact and spinalized rats. J Neurosci 22, 5265-5270.
51. Cook, A.J., Woolf, C.J., Wall, P.D. & McMahon, S.B. 1987. Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature 325, 151-153.
52. Creed R.S., Denny-Brown D., Eccles J.C., Liddell E.G.T. & Sherrington C.S. 1932. Reflex Activity of the Spinal Cord. Oxford University Press, London.
53. Crenna, P. & Frigo, C. 1984. Evidence of phase-dependent nociceptive reflexes during locomotion in man. Exp Neurol 85, 336-345.
54. Crown, E.D., Grau, J.W. & Meagher, M.W. 2004. Pain in a balance: noxious events engage opposing processes that concurrently modulate nociceptive reactivity. Behav Neurosci 118, 1418-1426.
55. Curatolo, M., Petersen-Felix, S., Arendt-Nielsen, L. & Zbinden, A.M. 1997. Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities. Anesthesiology 87, 785-794.
56. Davies, S.N. & Lodge, D. 1987. Evidence for involvement of N-methylaspartate receptors in "wind-up" of class 2 neurones in the dorsal horn of the rat. Brain Res 424, 402-406.
57. Decchi, B., Zalaffi, A., Spidalieri, R. et al. 1997. Spinal reflex pattern to foot nociceptive stimulation in standing humans. Electroencephalogr Clin Neurophysiol 105, 484-489.
58. Dickenson, A.H. & Sullivan, A.F. 1987. Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deep rat dorsal horn nociceptive neurons following C fibre stimulation. Neuropharmacology 26, 1235-1238.
59. Dietz, V. 2003. Spinal cord pattern generators for locomotion. Clin Neurophysiol 114, 1379-1389.
60. Dimitrijevic, M.R. & Nathan, P.W. 1968. Studies of spasticity in man. 3. Analysis of reflex activity evoked by noxious cutaneous stimulation. Brain 91, 349-368.
61. Dimitrijevic, M.R. & Nathan, P.W. 1970. Studies of spasticity in man. 4. changes in flexion reflex with repetitive cutaneous stimulation in spinal man. Brain 93, 743-768.
62. Dimitrijevic, M.R., Faganel, J., Gregoric, M., Nathan, P.W. & Trontelj, J.K. 1972. Habituation: effects of regular and stochastic stimulation. J Neurol Neurosurg Psychiatry 35, 234-242.
63. Dowman, R. 1991. Spinal and supraspinal correlates of nociception in man. Pain 45, 269-281.
64. Drewes, A.M., Schipper, K.P., Dimcevski, G. et al. 2003. Multi-modal induction and assessment of allodynia and hyperalgesia in the human oesophagus. Eur J Pain 7, 539-549.
65. Dubner, R. 1991. Neuronal plasticity in the spinal and medullary dorsal horns: a possible role in central pain mechanisms. In: K.L. Casey (ed.) Pain and Central Nervous System Disease: the Central Pain Syndromes, pp. 143-155. Raven Press, New York.
66. Duysens, J., Trippel, M., Hortsmann, G.A. & Dietz, V. 1990. Gating and reversal of reflexes in ankle muscles during human walking. Exp Brain Res 82, 351-358.
67. Eccles, R.M. & Lundberg, A. 1959a. Supraspinal control of interneurones mediating spinal reflexes. J Physiol London 147, 565-584.
68. Eccles, R.M. & Lundberg, A. 1959b. Synaptic actions in motoneurones by afferents which may evoke the flexion reflex. Arch Ital Biol 97, 199-221.
69. Ellrich, J. & Treede, R.-D. 1998. Convergence of nociceptive and non-nociceptive inputs onto spinal reflex pathways to the tibialis anterior muscle in humans. Acta Physiol Scand 163, 391-401.
70. Ellrich, J., Andersen, O.K., Treede, R.-D. & Arendt-Nielsen, L. 1998. Convergence of nociceptive and non-nociceptive input onto the medullary dorsal horn in man. Neuroreport 9, 3213-3217.
71. Engberg, I., Lundberg, A. & Ryall, R.W. 1968. Reticulospinal inhibition of transmission in reflex pathways. J Physiol 194, 201-223.
72. Ertekin, C., Ertekin, N. & Karcioglu, M. 1975. Conduction velocity along human nociceptive reflex afferent nerve fibres. J Neurol Neurosurg Psychiatry 38, 959-965.
73. Fields, H.L. & Basbaum, A.I. 1999. Central nervous systems mechanisms of pain modulation. In: P.D. Wall & R. Melzack (eds) Textbook of Pain, pp. 309-329. Churchill Livingstone, Edinburgh.
74. Forbes, A., Cobb, S. & Cattell, H. 1923. Electrical studies in mammalian reflexes. III. Immediate changes in the flexion reflex after spinal transection. Am J Physiol 65, 30-44.
75. Forssberg, H. 1979. Stumbling corrective reaction: a phase-dependent compensatory reaction during locomotion. J Neurophysiol 42, 936-953.
76. French, D.J., France, C.R., France, J.L. & Arnott, L.F. 2005. The influence of acute anxiety on assessment of nociceptive flexion reflex thresholds in healthy young adults. Pain 114, 358-363.
77. Garcia-Larrea, L. & Mauguiere, F. 1990. Electrophysiological assessment of nociception in normals and patients: the use of nociceptive reflexes. Electroencephalogr Clin Neurophysiol Suppl 41:102-118, 102-118.
78. Ge, H.Y., Collet, T., Mørch, C.D., Arendt-Nielsen, L. & Andersen, O.K. 2006. The human nociceptive withdrawal reflex is depressed more via segmental than heterosegmental intramuscular painful conditioning stimulation. Submitted.
79. Gjerstad, J., Tjølsen, A., Svendsen, F. & Hole, K. 1999. Inhibition of evoked C-fibre responses in the dorsal horn after contralateral intramuscular injection of capsaicin involves activation of descending pathways. Pain 80, 413-418.
80. Gjerstad, J., Tjolsen, A. & Hole, K. 2001. Induction of long-term potentiation of single wide dynamic range neurones in the dorsal horn is inhibited by descending pathways. Pain 91, 263-268.
81. Gossard, J.-P. & Hultborn, H. 1991. The organization of the spinal rhythm generation in locomotion. In: A. Wernig (ed.) Plasticity of Motoneuronal Connections, pp. 385-404. Elsevier Science Publishers BV, Amsterdam.
82. Gozariu, M., Bragard, D., Willer, J.C. & Le Bars, D. 1997. Temporal summation of C-fiber afferent inputs: competition between facilitatory and inhibitory effects on C-fiber reflex in the rat. J Neurophysiol 78, 3165-3179.
83. Grill, W.M. & Mortimer, J.T. 1997. Inversion of the current-distance relationship by transient depolarization. IEEE Trans Biomed Eng 44, 1-9.
84. Grimby, L. 1963a. Normal plantar response: integration of flexor and extensor reflex components. J Neurol Neurosurg Psychiatry 26, 39-50.
85. Grimby, L. 1963b. Pathological plantar response: disturbance of the normal integration of flexor and extensor reflex components. J Neurol Neurosurg Psychiatry 26, 314-321.
86. Grimby, L. 1965. Pathological plantar response. II. Loss of significance of stimulus site. J Neurol Neurosurg Psychiatry 28, 476-481.
87. Grönross, M. & Pertovaara, A. 1993. Capsaicin-induced central facilitation of a nociceptive flexion reflex in humans. Neurosci Lett 159, 215-218.
88. Guirimand, F., Dupont, X., Brasseur, L., Chauvin, M. & Bouhassira, D. 2000. The effects of ketamine on the temporal summation (Wind-Up) of the R(III) nociceptive flexion reflex and pain in humans. Anesth Analg 90, 408-414.
89. Hagbarth, K.E. 1952. Excitatory and inhibitory skin areas for flexor and extensor motoneurones. Acta Physiol Scand 26(Suppl. 94), 1-58.
90. Hagbarth, K.E. 1960. Spinal withdrawal reflexes in human lower limbs. J Neurol Neurosurg Psychiatry 23, 222-227.
91. Hardy, J.D., Jacobs, I. & Meixner, M.D. 1953. Thresholds of pain and reflex contraction as related to noxious stimulation. J Appl Physiol 5, 725-739.
92. Harris, J. & Clarke, R.W. 2003. Organisation of sensitisation of hind limb withdrawal reflexes from acute noxious stimuli in the rabbit. J Physiol 546, 251-265.
93. Heinricher, M.M., Martenson, M.E. & Neubert, M.J. 2004. Prostaglandin E2 in the midbrain periaqueductal gray produces hyperalgesia and activates pain-modulating circuitry in the rostral ventromedial medulla. Pain 110, 419-426.
94. Herrero, J.F., Laird, J.M. & Lopez-Garcia, J.A. 2000. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol 61, 169-203.
95. Hiersemenzel, L.P., Curt, A. & Dietz, V. 2000. From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurology 54, 1574-1582.
96. Holmberg, H. & Schouenborg, J. 1996. Postnatal development of the nociceptive withdrawal reflexes in the rat: a behavioural and electromyographic study. J Physiol London 493, 239-252.
97. Holmberg, H., Schouenborg, J., Yu, Y.B. & Weng, H.R. 1997. Developmental adaptation of rat nociceptive withdrawal reflexes after neonatal tendon transfer. J Neurosci 17, 2071-2078.
98. Holmqvist, B. & Lundberg, A. 1961. Differential supraspinal control of synaptic actions evoked by volleys in the flexion reflex afferents in alpha motoneurones. Acta Physiol Scand 54(Suppl. 186), 1-51.
99. Hugon, M. 1973. Exteroceptive reflexes to stimulation of the sural nerve in man. In: J.E. Desmedt (ed.) New Developments in Electromyography and Clinical Neurophysiology, pp. 713-729. Karger, Basel.
100. Hultborn, H. 2003. Changes in neuronal properties and spinal reflexes during development of spasticity following spinal cord lesions and stroke: studies in animal models and patients. J Rehabil Med 41, 46-55.
101. Hylden, J.L., Nahin, R.L., Traub, R.J. & Dubner, R. 1989. Expansion of receptive fields of spinal lamina I projection neurons in rats with unilateral adjuvant-induced inflammation: the contribution of dorsal horn mechanisms. Pain 37, 229-243.
102. Inglis, J.T., Kennedy, P.M., Wells, C. & Chua, R. 2002. The role of cutaneous receptors in the foot. Adv Exp Med Biol 508, 111-117.
103. Jankowska, E. & Lundberg, A. 1981. Interneurons in the spinal cord. TINS 4, 230-233.
104. Jankowska, E., Jukes, M.G.M., Lund, S. & Lundberg, A. 1967. The effect of DOPA. V. Reciprocal organization of pathways transmitting excitatory action to alpha motoneurones of flexors and extensors. Acta Physiol Scand 70, 369-388.
105. Jensen, T.S. & Yaksh, T.L. 1986. Examination of spinal monoamine receptors through which brainstem opiate-sensitive systems act in the rat. Brain Res 363, 114-127.
106. Jensen, T.S. & Yaksh, T.L. 1992. The antinociceptive activity of excitatory amino acids in the rat brainstem: an anatomical and pharmacological analysis. Brain Res 569, 255-267.
107. Kennedy, P.M. & Inglis, J.T. 2002. Distribution and behaviour of glabrous cutaneous receptors in the human foot sole. J Physiol 538, 995-1002.
108. Kiernan, B.D., Dane, J.R., Phillips, L.H. & Price, D.D. 1995. Hypnotic analgesia reduces R-III nociceptive reflex: further evidence concerning the multifactorial nature of hypnotic analgesia. Pain 60, 39-47.
109. Kniffki, K.-D., Schomburg, E.D. & Steffens, H. 1981. Synaptic effects from chemically activated fine muscle afferents upon α-motorneurones in decerebrate and spinal cats. Brain Res 206, 361-370.
110. Koltzenburg, M. & Handwerker, H.O. 1994. Differential ability of human cutaneous nociceptors to signal mechanical pain and to produce vasodilatation. J Neurosci 14, 1756-1765.
111. Kugelberg, E. 1948. Demonstration of A and C fibre components in the Babinsky plantar response and the pathological flexion reflex. Brain 71, 304-319.
112. Kugelberg, E., Eklund, K. & Grimby, L. 1960. An electromyographic study of the nociceptive reflexes of the lower limb. Mechanism of the plantar responses. Brain 83, 394-410.
113. Laird, J.M. & Cervero, F. 1990. Tonic descending influences on receptive-field properties of nociceptive dorsal horn neurons in sacral spinal cord of rat. J Neurophysiol 63, 1022-1032.
114. Laird, J.M.A., de la Rubia, P.G. & Cervero, F. 1995. Excitability changes of somatic and viscero-somatic nociceptive reflexes in the decerebrate-spinal rabbit: role of NMDA receptors. J Physiol 489, 545-555.
115. Le Bars, D., Villanueva, L., Bouhassira, D. & Willer, J.C. 1992. Diffuse noxious inhibitory controls (DNIC) in animals and in man. Patol Fiziol Eksp Ter 4, 55-65.
116. Le Bars, D., Gozariu, M. & Cadden, S.W. 2001. Animal models of nociception. Pharmacol Rev 53, 597-652.
117. Leem, J.W., Willis, W.D. & Chung, J.M. 1993. Cutaneous sensory receptors in the rat foot. J Neurophysiol 69, 1684-1699.
118. Levinsson, A., Garwicz, M. & Schouenborg, J. 1999a. Sensorimotor transformation in cat nociceptive withdrawal reflex system. Eur J Neurosci 11, 4327-4332.
119. Levinsson, A., Luo, X.L., Holmberg, H. & Schouenborg, J. 1999b. Developmental tuning in a spinal nociceptive system: effects of neonatal spinalization. J Neurosci 19, 10397-10403.
120. Lisin, V.V., Frankstein, S.I. & Rechtmann, M.B. 1973. The influence of locomotion on flexor reflex of the hind limb in cat and man. Exp Neurol 38, 180-183.
121. Lloyd, D.P.C. 1943. Neuron patterns controlling transmission of ipsilateral hind limb reflexes in cat. J Neurophysiol 6, 293-315.
122. Lundberg, A. 1979. Multisensory control of spinal reflex pathways. In: R. Granit & O. Pomeiano (eds) Reflex Control of Posture and Movement, Progress in Brain Research. pp. 11-28. Elsevier, Amsterdam.
123. Lundberg, A. 1982. Inhibitory control from the brain stem of transmission from primary afferents to motorneurons, primary afferent terminals and ascending pathways. In: B.G. Sjölund & A. Björklund (eds) Brain Stem Control of Spinal Mechanisms, pp. 179-224. Elsevier Biomedical Press, Amsterdam.
124. McIlroy, W.E., Bent, L.R., Potvin, J.R., Brooke, J.D. & Maki, B.E. 1999. Preparatory balance adjustments precede withdrawal response to noxious stimulation in standing humans. Neurosci Lett 267, 197-200.
125. Megirian, D. 1962. Bilateral facilitatory and inhibitory skin areas of spinal motoneurons of cat. J Neurophysiol 25, 127-137.
126. Meinck, H.M., Piesiur-Strehlow, B. & Koehler, W. 1981. Some principles of flexor reflex generation in human leg muscles. Electroencephalogr Clin Neurophysiol 52, 140-150.
127. Mendell, L.M. & Wall, P.D. 1965. Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres. Nature 206, 97-99.
128. Mørch, C.D., Andersen, O.K., Graven-Nielsen, T. & Arendt-Nielsen, L. 2007. Nociceptive withdrawal reflexes evoked by uniform-temperature laser heat stimulation of large skin areas in humans. J Neurosci Methods 160, 85-92.
129. Neubert, M.J., Kincaid, W. & Heinricher, M.M. 2004. Nociceptive facilitating neurons in the rostral ventromedial medulla. Pain 110, 158-165.
130. Nicol, D.J., Granat, M.H., Baxendale, R.H. & Tuson, S.J.M. 1995. Evidence for a human spinal stepping generator. Brain Res 684, 230-232.
131. Nielsen, J. & Arendt-Nielsen, L. 1998. The importance of stimulus configuration for temporal summation of first and second pain to repeated heat stimuli. Eur J Pain 2, 329-341.
132. Nielsen, J., Petersen, N. & Fedirchuk, B. 1997. Evidence suggesting a transcortical pathway from cutaneous foot afferents to tibialis anterior motoneurones in man. J Physiol 501, 473-484.
133. Oscarsson, O. 1973. Functional organization of spinocerebellar paths. In: A. Iggo (ed.) Handbook of Sensory Physiology. Somatosensory System, pp. 340-380. Springer-Verlag, Berlin.
134. Paquet, N., Tam, F. & Hui-Chan, C.W. 1996. Functional modulation of the human flexion and crossed extension reflexes by body position. Neurosci Lett 209, 215-217.
135. Plaghki, L., Bragard, D., Le, B.D., Willer, J.C. & Godfraind, J.M. 1998. Facilitation of a nociceptive flexion reflex in man by nonnoxious radiant heat produced by a laser. J Neurophysiol 79, 2557-2567.
136. Ponsford, S.N. 1988. Sensory conduction in medial and lateral plantar nerves. J Neurol Neurosurg Psychiatry 51, 188-191.
137. Price, D.D. 1972. Characteristics of second pain and flexion reflexes indicative of prolonged central summation. Exp Neurol 37, 371-387.
138. Price, D.D. 1988. Psychological and Neural Mechanisms of Pain. Raven Press, New York.
139. Price, D.D., Hu, J.W., Dubner, R. & Gracely, R.H. 1977. Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses. Pain 3, 57-68.
140. Price, D.D., Mao, J., Frenk, H. & Mayer, D.J. 1994. The N-methyl-D-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man. Pain 59, 165-174.
141. Rietdyk, S. & Patla, A.E. 1998. Context-dependent reflex control: some insights into the role of balance. Exp Brain Res 119, 251-259.
142. Roby-Brami, A. & Bussel, B. 1987. Long-latency spinal reflex in man after flexor reflex afferent stimulation. Brain 110, 707-725.
143. Rossi, A. & Decchi, B. 1994. Flexibility of lower limb reflex responses to painful cutaneous stimulation in standing humans: evidence of load-dependent modulation. J Physiol London 481, 521-532.
144. Rossi, A., Zalaffi, A. & Decchi, B. 1996. Interaction of nociceptive and non-nociceptive cutaneous afferents from foot sole in common reflex pathways to tibialis anterior motoneurons in humans. Brain Res 714, 76-86.
145. Sandrini, G., Serrao, M., Rossi, P. et al. 2005. The lower limb flexion reflex in humans. Prog Neurobiol 77, 353-395.
146. Sang, C.N., Max, M.B. & Gracely, R.H. 2003. Stability and reliability of detection thresholds for human A-Beta and A-delta sensory afferents determined by cutaneous electrical stimulation. J Pain Symptom Manage 25, 64-73.
147. Schmit, B.D., Hornby, T.G., Tysseling-Mattiace, V.M. & Benz, E.N. 2003. Absence of local sign withdrawal in chronic human spinal cord injury. J Neurophysiol 90, 3232-3241.
148. Schomburg, E.D. 1990. Spinal sensorimotor system and their supraspinal control. Neurosci Res 7, 265-340.
149. Schomburg, E.D. 1995. Multisensory control of movements at spinal levels and its supraspinal modulation. In: T. Mergner & F. Hlavacka (eds) Multisensory Control of Posture, pp. 1-7. Plenum Press, New York.
150. Schomburg, E.D. 1997. The FRA concept against a withdrawal reflex concept. Pain Forum 6, 124-126.
151. Schomburg, E.D. & Steffens, H. 1986. Synaptic responses of lumbar alpha-motorneurones to selective stimulation of cutaneous nociceptors and low threshold mechanoreceptors in the spinal cat. Exp Brain Res 62, 335-342.
152. Schomburg, E.D. & Steffens, H. 1998. Comparative analysis of L-DOPA actions on nociceptive and non-nociceptive spinal reflex pathways in the cat. Neurosci Res 31, 307-316.
153. Schomburg, E.D. & Steffens, H. 2002. Only minor spinal motor reflex effects from feline group IV muscle nociceptors. Neurosci Res 44, 213-223.
154. Schouenborg, J. 1984. Functional and topographical properties of field potentials evoked in rat dorsal horn by cutaneous C-fibre stimulation. J Physiol 356, 169-192.
155. Schouenborg, J. 1997. Nociceptive withdrawal reflexes as a model for spinal nociceptive transmission. Pain Forum 6, 116-118.
156. Schouenborg, J. 2004. Learning in sensorimotor circuits. Curr Opin Neurobiol 14, 693-697.
157. Schouenborg, J. & Dickenson, A. 1985. The effects of a distant noxious stimulation on A and C fibre-evoked flexion reflexes and neuronal activity in the dorsal horn of the rat. Brain Res 328, 23-32.
158. Schouenborg, J. & Kalliomäki, J. 1990. Functional organization of the nociceptive withdrawal reflexes. I. Activation of hindlimb muscles in the rat. Exp Brain Res 83, 67-78.
159. Schouenborg, J. & Sjölund, B.G. 1983. Activity evoked by A- and C-afferent fibers in rat dorsal horn neurons and its relation to a flexion reflex. J Neurophysiol 50, 1108-1121.
160. Schouenborg, J. & Weng, H.-R. 1994. Sensorimotor transformation in a spinal motor system. Exp Brain Res 100, 170-174.
161. Schouenborg, J., Holmberg, H. & Weng, H.-R. 1992a. Functional organization of the nociceptive withdrawal reflexes. II. Changes of excitability and receptive fields after spinalization in the rat. Exp Brain Res 90, 469-478.
162. Schouenborg, J., Weng, H.-R., Kalliomäki, J. & Holmberg, H. 1992b. Topographical organization of putative interneurones in nociceptive withdrawal reflex pathways in the rat. Eur J Neurosci, Supplement, 5, 193.
163. Schouenborg, J., Weng, H.-R. & Holmberg, H. 1994. Modular organization of spinal reflexes: a new hypothesis. NIPS 9, 261-265.
164. Schouenborg, J., Weng, H.-R., Kalliomäki, J. & Holmberg, H. 1995. A survey of spinal dorsal horn neurones encoding the spinal organization of withdrawal reflexes in the rat. Exp Brain Res 106, 19-27.
165. Serrao, M., Rossi, P., Sandrini, G. et al. 2004. Effects of diffuse noxious inhibitory controls on temporal summation of the RIII reflex in humans. Pain 112, 353-360.
166. Shahani, B. 1970. Flexor reflex afferent nerve fibres in man. J Neurol Neurosurg Psychiatry 33, 786-791.
167. Shahani, B.T. & Young, R.R. 1971. Human flexor reflexes. J Neurol Neurosurg Psychiatry 34, 616-627.
168. Sherrington, C.S. 1906. The Integrative Action of the Nervous system. Yale University Press, New Haven, CT.
169. Sherrington, C.S. 1910. Flexion-reflex of the limb, crossed extension-reflex and reflex stepping and standing. J Physiol London 40, 28-121.
170. Shin, H.K., Kim, J. & Chung, J.M. 1986. Inhibition and excitation of the nociceptive flexion reflex by conditioning stimulation of a peripheral nerve in the cat. Exp Neurol 92, 335-348.
171. Sivilotti, L.G., Thompson, S.W.N. & Woolf, C.J. 1993. Rate of rise of the cumulative depolarization evoked by repetitive stimulation of small-caliber afferents is a predictor of action potential windup in rat spinal neurons in vitro. J Neurophysiol 69, 1621-1631.
172. Sonnenborg, F.A., Andersen, O.K. & Arendt-Nielsen, L. 2000. Modular organization of excitatory and inhibitory reflex receptive fields elicited by electrical stimulation of the foot sole in man. Clin Neurophysiol 111, 2160-2169.
173. Sonnenborg, F.A., Andersen, O.K., Arendt-Nielsen, L. & Treede, R.-D. 2001. Withdrawal reflex organisation to electrical stimulation of the dorsal foot in humans. Exp Brain Res 136, 303-312.
174. Spadavecchia, C., Spadavecchia, L., Andersen, O.K. et al. 2002. Quantitative assessment of nociception in horses by use of the nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation. Am J Vet Res 63, 1551-1556.
175. Spaich, E.G., Arendt-Nielsen, L. & Andersen, O.K. 2004. Modulation of lower limb withdrawal reflexes during gait: a topographical study. J Neurophysiol 91, 258-266.
176. Spaich, E.G., Hinge, H.H., rendt-Nielsen, L. & Andersen, O.K. 2006. Modulation of the withdrawal reflex during hemiplegic gait: effect of stimulation site and gait phase. Clin Neurophysiol 117, 2482-2495.
177. Steffens, H. & Schomburg, E.D. 1993. Convergence in segmental reflex pathways from nociceptive and non-nociceptive afferents to α-motoneurons in the cat. J Physiol London 446, 191-211.
178. Terkelsen, A.J., Andersen, O.K., Hansen, P.O. & Jensen, T.S. 2001. Effects of heterotopic- and segmental counter-stimulation on the nociceptive withdrawal reflex in humans. Acta Physiol Scand 172, 211-217.
179. Terkelsen, A.J., Andersen, O.K., Molgaard, H., Hansen, J. & Jensen, T.S. 2004. Mental stress inhibits pain perception and heart rate variability but not a nociceptive withdrawal reflex. Acta Physiol Scand 180, 405-414.
180. Thompson, S.W., Woolf, C.J. & Sivilotti, L.G. 1993. Small-caliber afferent inputs produce a heterosynaptic facilitation of the synaptic responses evoked by primary afferent A-fibers in the neonatal rat spinal cord in vitro. J Neurophysiol 69, 2116-2128.
181. Treede, R.-D., Meyer, R.A., Raja, S.N. & Campbell, J.N. 1995. Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin. J Physiol London 483, 747-758.
182. Trulsson, M. 2001. Mechanoreceptive afferents in the human sural nerve. Exp Brain Res 137, 111-116.
183. Vierck, C.J., Cannon, R.L., Fry, G., Maixner, W. & Whitsel, B.L. 1997. Characteristics of temporal summation of second pain sensations elicited by brief contact of glabrous skin by a preheated thermode. J Neurophysiol 78, 992-1002.
184. Villanueva, L. & Le Bars, D. 1995. The activation of bulbospinal controls by peripheral nociceptive inputs: diffuse noxious inhibitory controls. Biol Res 28, 113-125.
185. Wagman, I. & Price, D.D. 1969. Response of dorsal horn cells of M. mulatta to cutaneous and sural nerve A and C fiber stimuli. J Neurophysiol 32, 803-817.
186. Waldenstrom, A., Thelin, J., Thimansson, E., Levinsson, A. & Schouenborg, J. 2003. Developmental learning in a pain-related system: evidence for a cross-modality mechanism. J Neurosci 23, 7719-7725.
187. Wall, P.D. & Woolf, C.J. 1984. Muscle but not cutaneous C-afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. J Physiol London 356, 443-458.
188. Weng, H.-R. & Schouenborg, J. 1996a. Cutaneous inhibitory receptive fields of withdrawal reflexes in the decerebrate spinal rat. J Physiol London 493, 253-265.
189. Weng, H.-R. & Schouenborg, J. 1996b. Nociceptive inhibition of withdrawal reflex responses increases over time in spinalized rats. Neuroreport 7, 1310-1314.
190. Weng, H.-R. & Schouenborg, J. 1998. On the cutaneous receptors contributing to withdrawal reflex pathways in the decerebrate spinal rat. Exp Brain Res 118, 71-77.
191. van Wezel, B.M., van Engelen, B., Gabreels, F.J., Gabreels-Festen, A.A. & Duysens, J. 2000. A beta fibers mediate cutaneous reflexes during human walking. J Neurophysiol 83, 2980-2986.
192. Willer, J.C. 1977. Comparative study of perceived pain and nociceptive flexion reflex in man. Pain 3, 69-80.
193. Willer, J.C. 1980. Anticipation of pain-produced stress: electrophysiological study in man. Physiol Behav 25, 49-51.
194. Willer, J.C. & Albe-Fessard, D. 1980. Electrophysiological evidence for a release of endogenous opiates in stress-induced analgesia in man. Brain Res 198, 419-426.
195. Willer, J.C. & Albe-Fessard, D. 1983. Further studies on the role of afferent input from relatively large diameter fibers in transmission of nociceptive messages in humans. Brain Res 278, 318-321.
196. Willer, J.C., Boureau, F. & Albe-Fessard, D. 1978. Role of large diameter cutaneous afferents in transmission of nociceptive messages: electrophysiological study in man. Brain Res 152, 358-364.
197. Willer, J.C., Boureau, F. & Albe-Fessard, D. 1979a. Supraspinal influence on nociceptive flexion reflex and pain sensation in man. Brain Res 179, 61-68.
198. Willer, J.C., Boureau, F. & Berny, J. 1979b. Nociceptive flexion reflexes elicited by noxious laser radiant heat in man. Pain 7, 15-20.
199. Willer, J.C., Roby, A. & LeBars, D. 1984. Psychophysical and electrophysiological approaches to the pain-relieving effects of heterotopic nociceptive stimuli. Brain 107, 1095-1112.
200. Willer, J.C., DeBroucker, T. & LeBars, D. 1989. Encoding of nociceptive thermal stimuli by diffuse noxious inhibitory controls in humans. J Neurophysiol 62, 1028-1038.
201. Willis, W.D. 1982. Control of Nociceptive Transmission in the Spinal Cord. Springer-Verlag, Berlin.
202. Wirski, J. & Hugon, M. 1972. Facilitation of cutaneous muscular reflex in man obtained by the reiteration of painful stimulus. In: G.G. Somjen (ed.) Neurophysiology Studied in Man: Proceedings of a Symposium Held in Paris at the Faculte des Sciences, 20-22 July 1971, pp. 350-365. Excerpta Medica, Amsterdam.
203. Woolf, C.J. 1983. Evidence for a central component of postinjury pain hypersensitivity. Nature 306, 686-688.
204. Woolf, C.J. & King, A.E. 1990. Dynamic alterations in the cutaneous mechanoreceptive fields of the dorsal horn neurons in the rat spinal cord. J Neurosci 10, 2717-2726.
205. Woolf, C.J. & Salter, M.W. 2000. Neuronal plasticity: increasing the gain in pain. Science 288, 1765-1769.
206. Woolf, C.J. & Swett, J.E. 1984. The cutaneous contribution to the hamstring flexor reflex in the rat: an electrophysiological and anatomical study. Brain Res 303, 299-312.
207. Woolf, C.J. & Thompson, S.W.N. 1991. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation: implications for the treatment of post-injury pain hypersensitivity states. Pain 44, 293-299.
208. Yang, J.F. & Stein, R.B. 1990. Phase-dependent reflex reversal in human leg muscles during walking. J Neurophysiol 63, 1109-1117.
209. You, H.J. & Arendt-Nielsen, L. 2005. Differences in responsiveness of spinal dorsal horn neurons and simultaneously recorded spinal withdrawal reflexes in different concentrations of halothane anesthetized spinal rats. Abstracts - XIth World Congress on Pain, p. 249.
210. You, H.J., Dahl, M.C., Chen, J. & Arendt-Nielsen, L. 2003. Simultaneous recordings of wind-up of paired spinal dorsal horn nociceptive neuron and nociceptive flexion reflex in rats. Brain Res 960, 235-245.
211. Yu, X.M. & Mense, S. 1990. Response properties and 'descending control of rat dorsal horn neurons with deep receptive fields. Neuroscience 39, 823-831.
212. Zachariae, R., Andersen, O.K., Bjerring, P., Jørgensen, M.M. & Arendt-Nielsen, L. 1998. Effects of an opioid antagonist on pain intensity and withdrawal reflexes during induction of hypnotic analgesia in high- and low-hypnotizable volunteers. Eur J Pain 2, 25-34.
213. Zehr, E.P. & Duysens, J. 2004. Regulation of arm and leg movement during human locomotion. Neuroscientist 10, 347-361.
214. Zehr, E.P. & Stein, R.B. 1999. What functions do reflexes serve during human locomotion? Prog Neurobiol 58, 185-205.