Emerging Role of Astroglia in Pain Hypersensitivity

Overview

Journal Jpn Dent Sci Rev

Publisher Elsevier

Specialty Dentistry

Date 2010 Feb 18

PMID 20161683

Citations 22

Authors

Ke Ren

Affiliations

Soon will be listed here.

Abstract

Recent studies suggest that astroglia, a major non-neuronal cell type in the central nervous system, actively participate in synaptic activity and potentially contribute to neurological disorders including chronic pain. Astroglia exhibit a hyperactive phenotype, also referred to as reactive astrocytosis, in response to peripheral injury. This process is often referred to as astroglial activation. By immunostaining against glial fibrillary acidic proteins, an intermediate cytoskeleton filament protein selectively localized to matured astrocytes, hypertrophy of astrocytes are clearly visible in the spinal cord dorsal horn and spinal trigeminal nucleus following a variety of injuries. Injury-related astroglial activation correlates with behavioral hyperalgesia and conversely, astroglial inhibition attenuates pain hypersensitivity. Astrocytes have a close anatomical relationship with neurons. Interactions between astrocytes and neurons contribute to the mechanisms of chronic pain. Astroglial activation is accompanied by initiation of cellular signal transduction pathways that lead to transcriptional gene regulation and release of a variety of chemical mediators or gliotransmitters, down-regulation of glutamate transporter activity that directly affects synaptic transmission, changes in gap junction proteins by which calcium waves spread, and alterations of the blood brain barrier. These coordinated changes in astroglial functions in turn modulate neuronal activity and facilitate pain transmission.

Citing Articles

Optogenetic inhibition of ventrolateral orbitofrontal cortex astrocytes facilitates ventrolateral periaqueductal gray glutamatergic activity to reduce hypersensitivity in infraorbital nerve injury rat model.

Islam J, Rahman M, Ali M, Kim H, Kc E, Park Y J Headache Pain. 2025; 26(1):41.

PMID: 39994518 PMC: 11854010. DOI: 10.1186/s10194-025-01977-6.

Post-Traumatic Trigeminal Neuropathy: Neurobiology and Pathophysiology.

Eliav T, Benoliel R, Korczeniewska O Biology (Basel). 2024; 13(3).

PMID: 38534437 PMC: 10967710. DOI: 10.3390/biology13030167.

GFAP-NpHR mediated optogenetic inhibition of trigeminal nucleus caudalis attenuates hypersensitive behaviors and thalamic discharge attributed to infraorbital nerve constriction injury.

Kc E, Islam J, Kim H, Park Y J Headache Pain. 2023; 24(1):137.

PMID: 37821818 PMC: 10566148. DOI: 10.1186/s10194-023-01669-z.

Anti-Inflammatory Activity of Synaptamide in the Peripheral Nervous System in a Model of Sciatic Nerve Injury.

Starinets A, Tyrtyshnaia A, Manzhulo I Int J Mol Sci. 2023; 24(7).

PMID: 37047247 PMC: 10093792. DOI: 10.3390/ijms24076273.

Mechanisms of Transmission and Processing of Pain: A Narrative Review.

Di Maio G, Villano I, Ilardi C, Messina A, Monda V, Iodice A Int J Environ Res Public Health. 2023; 20(4).

PMID: 36833753 PMC: 9964506. DOI: 10.3390/ijerph20043064.

References

Meller S, Dykstra C, Grzybycki D, Murphy S, Gebhart G . The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat. Neuropharmacology. 1994; 33(11):1471-8. DOI: 10.1016/0028-3908(94)90051-5. View

Ji R, Kawasaki Y, Zhuang Z, Wen Y, Decosterd I . Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway. Neuron Glia Biol. 2007; 2(4):259-69. PMC: 1949390. DOI: 10.1017/S1740925X07000403. View

Fiacco T, Agulhon C, Taves S, Petravicz J, Casper K, Dong X . Selective stimulation of astrocyte calcium in situ does not affect neuronal excitatory synaptic activity. Neuron. 2007; 54(4):611-26. DOI: 10.1016/j.neuron.2007.04.032. View

Menetski J, Mistry S, Lu M, Mudgett J, Ransohoff R, DeMartino J . Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses. Neuroscience. 2007; 149(3):706-14. DOI: 10.1016/j.neuroscience.2007.08.014. View

Halassa M, Fellin T, Takano H, Dong J, Haydon P . Synaptic islands defined by the territory of a single astrocyte. J Neurosci. 2007; 27(24):6473-7. PMC: 6672436. DOI: 10.1523/JNEUROSCI.1419-07.2007. View

Kuzumaki N, Narita M, Narita M, Hareyama N, Niikura K, Nagumo Y . Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice. Neurosci Lett. 2007; 415(1):22-7. DOI: 10.1016/j.neulet.2006.12.057. View

Ledeboer A, Gamanos M, Lai W, Martin D, Maier S, Watkins L . Involvement of spinal cord nuclear factor kappaB activation in rat models of proinflammatory cytokine-mediated pain facilitation. Eur J Neurosci. 2005; 22(8):1977-86. DOI: 10.1111/j.1460-9568.2005.04379.x. View

Diatchenko L, Nackley A, Slade G, Bhalang K, Belfer I, Max M . Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain. 2006; 125(3):216-224. DOI: 10.1016/j.pain.2006.05.024. View

Hashizume H, DeLeo J, Colburn R, Weinstein J . Spinal glial activation and cytokine expression after lumbar root injury in the rat. Spine (Phila Pa 1976). 2000; 25(10):1206-17. DOI: 10.1097/00007632-200005150-00003. View

10.

Leite M, Galland F, de Souza D, Guerra M, Bobermin L, Biasibetti R . Gap junction inhibitors modulate S100B secretion in astrocyte cultures and acute hippocampal slices. J Neurosci Res. 2009; 87(11):2439-46. DOI: 10.1002/jnr.22083. View

11.

Gao Y, Zhang L, Abdel Samad O, Suter M, Yasuhiko K, Xu Z . JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J Neurosci. 2009; 29(13):4096-108. PMC: 2682921. DOI: 10.1523/JNEUROSCI.3623-08.2009. View

12.

Lampe P, Lau A . Regulation of gap junctions by phosphorylation of connexins. Arch Biochem Biophys. 2001; 384(2):205-15. DOI: 10.1006/abbi.2000.2131. View

13.

Chiang C, Wang J, Xie Y, Zhang S, Hu J, Dostrovsky J . Astroglial glutamate-glutamine shuttle is involved in central sensitization of nociceptive neurons in rat medullary dorsal horn. J Neurosci. 2007; 27(34):9068-76. PMC: 6672204. DOI: 10.1523/JNEUROSCI.2260-07.2007. View

14.

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

15.

Ping Dai R, He B, Dheen S, Tay S . Acute cardiac injury induces glial cell response and activates extracellular signaling-regulated kinase-1 and -2 in the spinal cord of Wistar rats. Neurosci Lett. 2004; 366(1):34-8. DOI: 10.1016/j.neulet.2004.05.018. View

16.

Zhang J, Cheng H, Chen J, Yi F, Li W, Luan R . Involvement of activated astrocyte and microglia of locus coeruleus in cardiac pain processing after acute cardiac injury. Neurol Res. 2009; 31(4):432-8. DOI: 10.1179/174313208X355486. View

17.

Nesic O, Lee J, Johnson K, Ye Z, Xu G, Unabia G . Transcriptional profiling of spinal cord injury-induced central neuropathic pain. J Neurochem. 2005; 95(4):998-1014. DOI: 10.1111/j.1471-4159.2005.03462.x. View

18.

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

19.

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

20.

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