Supraspinal Glial-neuronal Interactions Contribute to Descending Pain Facilitation

Overview

Journal J Neurosci

Specialty Neurology

Date 2008 Oct 17

PMID 18923025

Citations 137

Authors

Feng Wei

Wei Guo

Shiping Zou

Ke Ren

Ronald Dubner

Affiliations

Soon will be listed here.

Abstract

Spinal glial reaction and proinflammatory cytokine induction play an important role in the development of chronic pain states after tissue and nerve injury. The present study investigated the cellular and molecular mechanisms underlying descending facilitation of neuropathic pain with an emphasis on supraspinal glial-neuronal relationships. An early and transient reaction of microglia and prolonged reaction of astrocytes were found after chronic constriction injury (CCI) of the rat infraorbital nerve in the rostral ventromedial medulla (RVM), a major component of brainstem descending pain modulatory circuitry. There were prolonged elevations of cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) after CCI, and they were expressed in RVM astrocytes at 14 d after injury. Intra-RVM injection of microglial and astrocytic inhibitors attenuated mechanical hyperalgesia and allodynia at 3 and 14 d after CCI, respectively. Moreover, TNFR1 and IL-1R, receptors for TNF-alpha and IL-1beta, respectively, were expressed primarily in RVM neurons exhibiting immunoreactivity to the NMDA receptor (NMDAR) subunit NR1. CCI increased TNFR1 and IL-1R levels and NR1 phosphorylation in the RVM. Neutralization of endogenous TNF-alpha and IL-1beta in the RVM significantly reduced CCI-induced behavioral hypersensitivity and attenuated NR1 phosphorylation. Finally, intra-RVM administration of recombinant TNF-alpha or IL-1beta upregulated NR1 phosphorylation and caused a reversible and NMDAR-dependent allodynia in normal rats, further suggesting that TNF-alpha and IL-1beta couple glial hyperactivation with NMDAR function. These studies have addressed a novel contribution of supraspinal astrocytes and associated cytokines as well as central glial-neuronal interactions to the enhancement of descending facilitation of neuropathic pain.

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References

Hirose S, Umetani Y, Amitani M, Hosoi R, Momosaki S, Hatazawa J . Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate. Neurosci Lett. 2007; 415(3):259-63. DOI: 10.1016/j.neulet.2007.01.031. View

Scholz J, Broom D, Youn D, Mills C, Kohno T, Suter M . Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. J Neurosci. 2005; 25(32):7317-23. PMC: 6725303. DOI: 10.1523/JNEUROSCI.1526-05.2005. View

Raghavendra V, Tanga F, DeLeo J . Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci. 2004; 20(2):467-73. DOI: 10.1111/j.1460-9568.2004.03514.x. View

Sweitzer S, Schubert P, DeLeo J . Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain. J Pharmacol Exp Ther. 2001; 297(3):1210-7. View

Dubner R, Ren K . Brainstem mechanisms of persistent pain following injury. J Orofac Pain. 2005; 18(4):299-305. View

Yang S, Liu Z, Wen L, Qiao H, Zhou W, Zhang Y . Interleukin-1beta enhances NMDA receptor-mediated current but inhibits excitatory synaptic transmission. Brain Res. 2005; 1034(1-2):172-9. DOI: 10.1016/j.brainres.2004.11.018. View

Sommer C, Kress M . Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004; 361(1-3):184-7. DOI: 10.1016/j.neulet.2003.12.007. View

Imamura Y, Kawamoto H, Nakanishi O . Characterization of heat-hyperalgesia in an experimental trigeminal neuropathy in rats. Exp Brain Res. 1997; 116(1):97-103. DOI: 10.1007/pl00005748. View

Pertovaara A, Wei H, Hamalainen M . Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats. Neurosci Lett. 1996; 218(2):127-30. DOI: 10.1016/s0304-3940(96)13136-0. View

10.

Ren K, Dubner R . Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008; 21(5):570-9. PMC: 2735048. DOI: 10.1097/ACO.0b013e32830edbdf. View

11.

Guo W, Robbins M, Wei F, Zou S, Dubner R, Ren K . Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J Neurosci. 2006; 26(1):126-37. PMC: 6674294. DOI: 10.1523/JNEUROSCI.3686-05.2006. View

12.

Nutile-McMenemy N, Elfenbein A, DeLeo J . Minocycline decreases in vitro microglial motility, beta1-integrin, and Kv1.3 channel expression. J Neurochem. 2007; 103(5):2035-46. DOI: 10.1111/j.1471-4159.2007.04889.x. View

13.

Paulsen R, Contestabile A, Villani L, Fonnum F . An in vivo model for studying function of brain tissue temporarily devoid of glial cell metabolism: the use of fluorocitrate. J Neurochem. 1987; 48(5):1377-85. DOI: 10.1111/j.1471-4159.1987.tb05674.x. View

14.

Guo W, Wang H, Watanabe M, Shimizu K, Zou S, Lagraize S . Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J Neurosci. 2007; 27(22):6006-18. PMC: 2676443. DOI: 10.1523/JNEUROSCI.0176-07.2007. View

15.

Tawfik V, Regan M, Haenggeli C, LaCroix-Fralish M, Nutile-McMenemy N, Perez N . Propentofylline-induced astrocyte modulation leads to alterations in glial glutamate promoter activation following spinal nerve transection. Neuroscience. 2008; 152(4):1086-92. PMC: 2423012. DOI: 10.1016/j.neuroscience.2008.01.065. View

16.

Tanga F, Raghavendra V, Nutile-McMenemy N, Marks A, DeLeo J . Role of astrocytic S100beta in behavioral hypersensitivity in rodent models of neuropathic pain. Neuroscience. 2006; 140(3):1003-10. DOI: 10.1016/j.neuroscience.2006.02.070. View

17.

Wei F, Vadakkan K, Toyoda H, Wu L, Zhao M, Xu H . Calcium calmodulin-stimulated adenylyl cyclases contribute to activation of extracellular signal-regulated kinase in spinal dorsal horn neurons in adult rats and mice. J Neurosci. 2006; 26(3):851-61. PMC: 6675366. DOI: 10.1523/JNEUROSCI.3292-05.2006. View

18.

Viviani B, Gardoni F, Bartesaghi S, Corsini E, Facchi A, Galli C . Interleukin-1 beta released by gp120 drives neural death through tyrosine phosphorylation and trafficking of NMDA receptors. J Biol Chem. 2006; 281(40):30212-22. DOI: 10.1074/jbc.M602156200. View

19.

Burgess S, Gardell L, Ossipov M, Philip Malan Jr T, Vanderah T, Lai J . Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain. J Neurosci. 2002; 22(12):5129-36. PMC: 6757729. View

20.

Sun S, Cao H, Han M, Li T, Zhao Z, Zhang Y . Evidence for suppression of electroacupuncture on spinal glial activation and behavioral hypersensitivity in a rat model of monoarthritis. Brain Res Bull. 2007; 75(1):83-93. DOI: 10.1016/j.brainresbull.2007.07.027. View