P2Y Receptor Upregulation in Satellite Glial Cells is Involved in Neuropathic Pain Induced by HIV Glycoprotein 120 and 2',3'-dideoxycytidine

Overview

Journal Purinergic Signal

Publisher Springer

Date 2017 Nov 22

PMID 29159762

Citations 16

Authors

Zhihua Yi

Lihui Xie

Congfa Zhou

Huilong Yuan

Shuai Ouyang

Zhi Fang

Shanhong Zhao

Tianyu Jia

Lifang Zou

Shouyu Wang

Yun Xue

Bing Wu

Yun Gao

Guilin Li

Shuangmei Liu

Hong Xu

Changshui Xu

Chunping Zhang

Shangdong Liang

Affiliations

Soon will be listed here.

Abstract

The direct neurotoxicity of HIV and neurotoxicity of combination antiretroviral therapy medications both contribute to the development of neuropathic pain. Activation of satellite glial cells (SGCs) in the dorsal root ganglia (DRG) plays a crucial role in mechanical and thermal hyperalgesia. The P2Y receptor expressed in SGCs of the DRG is involved in pain transmission. In this study, we explored the role of the P2Y receptor in neuropathic pain induced by HIV envelope glycoprotein 120 (gp120) combined with ddC (2',3'-dideoxycytidine). A rat model of gp120+ddC-induced neuropathic pain was used. Peripheral nerve exposure to HIV-gp120+ddC increased mechanical and thermal hyperalgesia in gp120+ddC-treated model rats. The gp120+ddC treatment increased expression of P2Y receptor mRNA and protein in DRG SGCs. In primary cultured DRG SGCs treated with gp120+ddC, the levels of [Ca] activated by the P2Y receptor agonist 2-(Methylthio) adenosine 5'-diphosphate trisodium salt (2-MeSADP) were significantly increased. P2Y receptor shRNA treatment inhibited 2-MeSADP-induced [Ca] in primary cultured DRG SGCs treated with gp120+ddC. Intrathecal treatment with a shRNA against P2Y receptor in DRG SGCs reduced the release of pro-inflammatory cytokines, decreased phosphorylation of p38 MAPK in the DRG of gp120+ddC-treated rats. Thus, downregulating the P2Y receptor relieved mechanical and thermal hyperalgesia in gp120+ddC-treated rats.

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References

Blum E, Procacci P, Conte V, Sartori P, Hanani M . Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia. Exp Cell Res. 2016; 350(1):236-241. DOI: 10.1016/j.yexcr.2016.11.026. View

Tu G, Li G, Peng H, Hu J, Liu J, Kong F . P2X(7) inhibition in stellate ganglia prevents the increased sympathoexcitatory reflex via sensory-sympathetic coupling induced by myocardial ischemic injury. Brain Res Bull. 2013; 96:71-85. DOI: 10.1016/j.brainresbull.2013.05.004. View

Takeda M, Tanimoto T, Kadoi J, Nasu M, Takahashi M, Kitagawa J . Enhanced excitability of nociceptive trigeminal ganglion neurons by satellite glial cytokine following peripheral inflammation. Pain. 2006; 129(1-2):155-66. DOI: 10.1016/j.pain.2006.10.007. View

Keswani S, Jack C, Zhou C, Hoke A . Establishment of a rodent model of HIV-associated sensory neuropathy. J Neurosci. 2006; 26(40):10299-304. PMC: 6674617. DOI: 10.1523/JNEUROSCI.3135-06.2006. View

Suadicani S, Cherkas P, Zuckerman J, Smith D, Spray D, Hanani M . Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia. Neuron Glia Biol. 2009; 6(1):43-51. PMC: 2897940. DOI: 10.1017/S1740925X09990408. View

Schutz S, Robinson-Papp J . HIV-related neuropathy: current perspectives. HIV AIDS (Auckl). 2013; 5:243-51. PMC: 3775622. DOI: 10.2147/HIV.S36674. View

Katagiri A, Shinoda M, Honda K, Toyofuku A, Sessle B, Iwata K . Satellite glial cell P2Y12 receptor in the trigeminal ganglion is involved in lingual neuropathic pain mechanisms in rats. Mol Pain. 2012; 8:23. PMC: 3386019. DOI: 10.1186/1744-8069-8-23. View

Joseph E, Chen X, Khasar S, Levine J . Novel mechanism of enhanced nociception in a model of AIDS therapy-induced painful peripheral neuropathy in the rat. Pain. 2004; 107(1-2):147-58. DOI: 10.1016/j.pain.2003.10.010. View

Zhang X, Chen Y, Wang C, Huang L . Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia. Proc Natl Acad Sci U S A. 2007; 104(23):9864-9. PMC: 1887586. DOI: 10.1073/pnas.0611048104. View

10.

Fields R, Burnstock G . Purinergic signalling in neuron-glia interactions. Nat Rev Neurosci. 2006; 7(6):423-36. PMC: 2062484. DOI: 10.1038/nrn1928. View

11.

Horvath G, Goloncser F, Csolle C, Kiraly K, Ando R, Baranyi M . Central P2Y12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents. Neurobiol Dis. 2014; 70:162-78. PMC: 4148180. DOI: 10.1016/j.nbd.2014.06.011. View

12.

Ceruti S, Fumagalli M, Villa G, Verderio C, Abbracchio M . Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures. Cell Calcium. 2007; 43(6):576-90. DOI: 10.1016/j.ceca.2007.10.003. View

13.

Oshinaike O, Akinbami A, Ojo O, Ogbera A, Okubadejo N, Ojini F . Influence of Age and Neurotoxic HAART Use on Frequency of HIV Sensory Neuropathy. AIDS Res Treat. 2012; 2012:961510. PMC: 3337556. DOI: 10.1155/2012/961510. View

14.

Yuan S, Shi Y, Chen J, Zhou X, Li G, Gelman B . Gp120 in the pathogenesis of human immunodeficiency virus-associated pain. Ann Neurol. 2014; 75(6):837-50. PMC: 4077969. DOI: 10.1002/ana.24139. View

15.

Zhang Z, Liu X, Lu S, Yu A, Fu Z . Increased pain in response to mechanical or thermal stimulation in a rat model of incision-induced pain with nicotine dependence and withdrawal. Exp Ther Med. 2013; 5(4):1063-1066. PMC: 3627443. DOI: 10.3892/etm.2013.963. View

16.

Castillo C, Norcini M, Martin Hernandez L, Correa G, Blanck T, Recio-Pinto E . Satellite glia cells in dorsal root ganglia express functional NMDA receptors. Neuroscience. 2013; 240:135-46. DOI: 10.1016/j.neuroscience.2013.02.031. View

17.

Sachs D, Cunha F, Poole S, Ferreira S . Tumour necrosis factor-alpha, interleukin-1beta and interleukin-8 induce persistent mechanical nociceptor hypersensitivity. Pain. 2002; 96(1-2):89-97. DOI: 10.1016/s0304-3959(01)00433-x. View

18.

Costa F, Neto F . [Satellite glial cells in sensory ganglia: its role in pain]. Rev Bras Anestesiol. 2014; 65(1):73-81. DOI: 10.1016/j.bjan.2013.07.013. View

19.

Pinheiro A, Paramos-de-Carvalho D, Certal M, Costa C, Magalhaes-Cardoso M, Ferreirinha F . Bradykinin-induced Ca2+ signaling in human subcutaneous fibroblasts involves ATP release via hemichannels leading to P2Y12 receptors activation. Cell Commun Signal. 2013; 11:70. PMC: 3848849. DOI: 10.1186/1478-811X-11-70. View

20.

Nasirinezhad F, Jergova S, Pearson J, Sagen J . Attenuation of persistent pain-related behavior by fatty acid amide hydrolase (FAAH) inhibitors in a rat model of HIV sensory neuropathy. Neuropharmacology. 2014; 95:100-9. PMC: 4457709. DOI: 10.1016/j.neuropharm.2014.11.024. View