Processing noxious information at the subnucleus reticularis dorsalis (SRD) of anesthetized cats: wind-up mechanisms.
With the exception of one monkey's study, where wind-up was not reported, electrophysiological data from SRD neurons were obtained in rodents where they show wind-up. This work was designed to examine the response properties of SRD neurons in anesthetized cats to study how general the data from rats may be. Since cat's SRD cells showed wind-up, its underlying mechanisms were approached, an issue not previously addressed at supraspinal level. Electrical stimulation, extracellular (combined with microiontophoresis) and intracellular techniques revealed that A delta information reaches the SRD via the ventrolateral cord, whereas C information preferentially follows a dorsal route. Wind-up was usually generated by spinal and peripheral stimulation, but it was also evoked either by stimulating the nucleus reticularis gigantocellularis (NRGc), even after spinal cord section and bilateral full thickness removal of the cerebral cortex, or by applying microiontophoretic pulses of l-glutamate at 0.3-1 Hz. Wind-up relied on afferent repetitive activity gradually depolarizing the SRD neurons leading 3-4.5 Hz subthreshold membrane rhythmic activity to threshold. Riluzole retarded wind-up generation and decreased the number of spikes per stimulus during wind-up. GABA or glycine abolished spontaneous and sensory-evoked activity and bicuculline, but not strychnine, increased spontaneous and stimulus-evoked activity. These results demonstrate that wind-up at the SRD is not merely the reflection of spinal wind-up, but (i) can be locally generated, (ii) is partially dependent upon persistent sodium currents, and (iii) is under the modulation of a tonic GABAa-dependent inhibition decreasing SRD excitability. Injury and/or inflammation producing tonic C-fiber activation will surpass tonic inhibition generating wind-up.
Soto
Cristina
C
Department of Physiology, Faculty of Medicine, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.
Martín-Cora
Francisco J
FJ
Leiras
Roberto
R
Velo
Patricia
P
Canedo
Antonio
A
D000344:Afferent Pathways / Q000503:physiopathology*; D000758:Anesthesia; D000818:Animals; D002415:Cats; D005260:Female; D008297:Male; D008526:Medulla Oblongata / Q000503:physiopathology*; D009474:Neurons; D010146:Pain / Q000503:physiopathology*; D013116:Spinal Cord / Q000503:physiopathology*
Almeida A, Tavares I, Lima D, Coimbra A. Descending projections from the medullary dorsal reticular nucleus make synaptic contacts with spinal cord lamina I cells projecting to that nucleus: an electron microscopic tracer study in the rat. Neuroscience. 1993;55:1093-1106.
Almeida A, Tavares I, Lima D. Projection sites of superficial or deep dorsal horn in the dorsal reticular nucleus. Neuroreport. 1995;6:1245-1248.
Almeida A, Tavares I, Lima D. Reciprocal connections between the medullary dorsal reticular nucleus and the spinal dorsal horn in the rat. Eur J Pain. 2000;4:373-387.
Apkarian AV, Hodge CJ Jr. The primate spinothalamic pathways II. The cells of origin of the dorsolateral and ventral spinothalamic pathways. J Comp Neurol. 1989;288:474-492.
Apkarian AV, Stevens RT, Hodge CJ. Funicular location of ascending axons of lamina I cells in the cat spinal cord. Brain Res. 1985;334:160-164.
Baranauskas G, Nistri A. Sensitization of pain pathways in the spinal cord: cellular mechanisms. Prog Neurobiol. 1998;54:349-365.
Bardoni R, Torsney C, Tong C-K, Prandini M, MacDermott AB. Presynaptic NMDA receptors modulate glutamate release from primary sensory neurons in rat spinal dorsal horn. J Neurosci. 2004;17:2774-2781.
Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci. 1984;7:309-338.
Basbaum AI, Clanton CH, Fields HL. Three bulbospinal pathways from the rostral medulla of the cat: an autoradiographic study of pain modulating systems. J Comp Neurol. 1978;178:209-224.
Bernard JF, Villanueva L, Carroue J, Le Bars D. Efferent projections from the subnucleus reticularis dorsalis (SRD): a Phaseolus vulgaris leucoagglutinin study in the rat. Neurosci Lett. 1990;122:257-262.
Bing Z, Villanueva L, Le Bars D. Ascending pathways in the spinal cord involved in the activation of subnucleus reticularis dorsalis neurons in the medulla of the rat. J Neurophysiol. 1990;63:424-438.
Bouhassira D, Villanueva L, Bing Z, Le Bars D. Involvement of the subnucleus reticularis dorsalis in diffuse noxious inhibitory controls in the rat. Brain Res. 1992;595:353-357.
Budai D, Sergey G, Khasabov SG, Mantyh PW, Simone DA. NK-1 receptors modulate the excitability of ON cells in the rostral ventromedial medulla. J Neurophysiol. 2007;97:1388-1395.
Burton H. Somatic sensory properties of caudal bulbar reticular neurons in the cat (Felis domestica). Brain Res. 1968;11:357-372.
Canedo A, Aguilar J. Spatial and cortical influences exerted on cuneothalamic and thalamocortical neurons of the cat. Eur J Neurosci. 2000;12:2515-2533.
Carlson JD, Maire JJ, Martenson ME, Heinricher MM. Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. J Neurosci. 2007;27:13222-13231.
Cope DW, Hughes SW, Crunelli V. GABAa receptor-mediated tonic inhibition in thalamic neurons. J Neurosci. 2005;25:11553-11563.
Cramer NP, Li Y, Keller A. The whisking rhythm generator: a novel mammalian network for the generation of movement. J Neurophysiol. 2007;97:2148-2158.
Davies SN, Lodge D. Evidence for involvement of N-methylaspartate receptors in “wind-up” of class 2 neurones in the dorsal horn of the rat. Brain Res. 1987;424:402-406.
Del Negro CA, Morgado-Valle C, Feldman JL. Respiratory rhythm: an emergent network property? Neuron. 2002;34:821-830.
Dickenson AH, Sullivan AF. Evidence for a role of the NMDA receptors in the frequency dependent potentiation of dorsal horn nociceptive neurones following C fibre stimulation. Neuropharmacology. 1987;26:1235-1238.
Dugast C, Almeida A, Lima D. The medullary dorsal reticular nucleus enhances the responsiveness of spinal nociceptive neurons to peripheral stimulation in the rat. Eur J Neurosci. 2003;18:580-588.
Farrant M, Nusser Z. Variations on an inhibitory theme: phasic and tonic activation of GABAa receptors. Nat Rev Neurosci. 2005;6:215-229.
Fossat P, Sibon I, Le Masson G, Landry M, Nagy F. l-type calcium channels and NMDA receptors: a determinant duo for short-term nociceptive plasticity. Eur J Neurosci. 2007;25:127-135.
Fujino Y, Koyama N, Yokota T. Differential distribution of three types of nociceptive neurons within the caudal bulbar reticular formation in the cat. Brain Res. 1996;715:225-229.
Guilbaud G, Peschanski M, Gautron M. Functional changes in ventrobasal thalamic neurones responsive to noxious and non-noxious cutaneous stimuli after chloralose treatment: new evidence for the presence of pre-existing “silent connections” in the adult nervous system? Pain. 1981;11:9-19.
Herrero JF, Laird JMA, López-García JA. Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol. 2000;61:169-203.
Huang Q, Zhou D, DiFiglia M. Neurobiotin, a useful neuroanatomical tracer, retrograde and transneuronal tract-tracing and for in vitro labelling of neurons. J Neurosci Methods. 1992;41:31-43.
Jones MW, Hodge CJ, Apkarian AV, Stevens RTA. Dorsolateral spinothalamic pathway in the cat. Brain Res. 1985;335:188-193.
Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA. Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci. 2002;22:9086-9098.
Khasabov SG, Ghilardi JR, Mantyh PW, Donald A, Simone DA. Spinal neurons that express NK-1 receptors modulate descending controls that project through the dorsolateral funiculus. J Neurophysiol. 2005;93:998-1006.
Klop EM, Mouton LJ, Hulsebosch R, Boers J, Holstege G. In cat four times as many lamina I neurons project to the parabrachial nuclei and twice as many to the periaqueductal gray as to the thalamus. Neuroscience. 2005;134:189-197.
Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC). Part I: Effects on dorsal horn convergent neurons in the rat. Pain. 1979;6:283-304.
Lima D. A spinomedullary projection terminating in the dorsal reticular nucleus of the rat. Neuroscience. 1979;34:577-589.
Lima D. A spinomedullary projection terminating in the dorsal reticular nucleus of the rat. Neuroscience. 1990;34:577-589.
Martin RJ, Apkarian AV, Hodge CJ Jr. Ventrolateral and dorsolateral ascending spinal cord pathway influence on thalamic nociception in cat. J Neurophysiol. 1990;64:1400-1412.
Mendell LM, Wall PD. Responses of single dorsal cells to peripheral cutaneous unmyelinated fibers. Nature. 1965;206:97-99.
Morisset V, Nagy F. Plateau potential-dependent wind-up of the response to primary afferent stimuli in rat dorsal horn neurons. Eur J Neurosci. 2000;12:3087-3095.
Newman DB. Distinguishing rat brainstem reticulospinal nuclei by their neuronal morphology. I: Medullary nuclei. J Hirnforsch. 1985;26:187-226.
Pace RW, Mackay DD, Feldman JL, Del Negro CA. Role of persistent sodium current in mouse preBötzinger complex neurons and respiratory rhythm generation. J Physiol. 2007;580:485-496.
Porreca F, Ossipov MH, Gebhart GF. Chronic pain and medullar descending facilitation. Trends Neurosci. 2002;25:319-325.
Price DD, Hull CD, Buchwald NA. Intracellular responses of dorsal horn cells to cutaneous and sural nerve A and C fiber stimuli. Exp Neurol. 1971;33:291-309.
Ptak K, Zummo GG, Alheid GF, Tkatch T, Surmeier DJ, McCrimmon DR. Sodium currents in medullary neurons isolated from the pre-Bötzinger complex region. J Neurosci. 2005;25:5159-5170.
Raboisson P, Dallel R, Bernard JF, Le Bars D, Villanueva L. Organization of efferent projections from the spinal cervical enlargement to the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: a PHA-L study in the rat. J Comp Neurol. 1996;367:503-517.
Reboreda A, Sánchez E, Romero M, Lamas JA. Intrinsic spontaneous activity and subthreshold oscillations in neurons of the rat dorsal column nuclei in culture. J Physiol. 2003;551:191-205.
Russo RE, Hounsgaard RJ. Short-term plasticity in turtle dorsal horn neurons mediated by l-type Ca2+ channels. Neuroscience. 1994;61:191-197.
Schouenborg J, Dickenson AH. 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. 1985;328:23-32.
Schouenborg J, Sjölund BH. Activity evoked by A- and C-afferent fibers in the rat dorsal horn neurons and its relation to a flexion reflex. J Neurophysiol. 1983;50:1108-1121.
Suzuki R, Morcuende S, Webber M, Hunt S, Dickenson A. Superficial NK1 expressing neurons control spinal excitability by activation of descending pathways. Nat Neurosci. 2002;5:1319-1326.
Tavares I, Lima D. Descending projections from the caudal medulla oblongata to the superficial or deep dorsal horn of the rat spinal cord. Exp Brain Res. 1994;99:455-463.
Thompson SWN, Dray A, Urban L. Injury-induced plasticity of spinal reflex activity: NK1 neurokinin receptor activation and enhanced A- and C-fiber mediated responses in the rat spinal cord in vitro. J Neurosci. 1994;14:3672-3687.
Todd AJ, McGill MM, Shehab SA. Neurokinin 1 receptor expression by neurons in lamina I, III and IV of the rat spinal dorsal horn that project to the brain stem. Eur J Neurosci. 2000;12:689-700.
Urbani A, Belluzzi O. Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur J Neurosci. 2000;12:3567-3574.
Valverde F. Reticular formation of the pons and medulla oblongata. A Golgi study. J Comp Neurol. 1961;116:71-99.
Van Drongelen W, Koch H, Elsen FP, Lee HC, Mrejeru A, Doren E, et al. Role of persistent sodium current in bursting activity of mouse neocortical networks in vitro. J Neurophysiol. 2006;96:2564-2577.
Villanueva L, Le Bars D. The activation of bulbo-spinal controls by peripheral nociceptive inputs: diffuse noxious inhibitory controls. Biol Res. 1995;28:113-125.
Villanueva L, Bernard JF, Le Bars D. Distribution of spinal cord projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol. 1995;353:11-32.
Villanueva L, Bing Z, Bouhassira D, Le Bars D. Encoding of electrical, thermal and mechanical noxious stimuli by subnucleus reticularis dorsalis neurons in the rat medulla. J Neurophysiol. 1989;61:391-402.
Villanueva L, Bouhassira D, Bing Z, Le Bars D. Convergence of heterotopic nociceptive information onto subnucleus reticularis dorsalis neurons in the rat medulla. J Neurophysiol. 1988;60:980-1009.
Villanueva L, Cliffer KD, Sorkin D, Le Bars D, Willis WD. Convergenge of heterotopic nociceptive information onto neurons of the caudal medullary reticular formation in the monkey. J Neurophysiol. 1990;63:1118-1127.
Villanueva L, De Pommery J, Menétrey D, Le Bars D. Spinal afferent projections to subnucleus reticularis dorsalis in the rat. Neurosci Lett. 1991;134:98-102.
Wei F, Dubner R, Ren K. Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain. 1999;80:127-141.
Woolf CJ. Windup and central sensitisation are not equivalent. Pain. 1996;66:105-108.
Wu N, Enomoto A, Tanaka S, Hsiao CF, Nykamp DQ, Izhikevich E, et al. Persistent sodium currents in mesencephalic v neurons participate in burst generation and control of membrane excitability. J Neurophysiol. 2005;93:2710-2722.