Spinal astrocytic activation is involved in a virally-induced rat model of neuropathic pain

• Published in: PloS one 2011-09, Vol.6 (9), p.e23059-e23059
• Main Authors: Zhang, Gui-He, Lv, Miao-Miao, Wang, Shuang, Chen, Lei, Qian, Nian-Song, Tang, Yu, Zhang, Xu-Dong, Ren, Peng-Cheng, Gao, Chang-Jun, Sun, Xu-De, Xu, Li-Xian
• Format: Article
• Language: English
• Subjects: Activation; Analgesics; Anesthesiology; Animals; Aspartate; Aspartic acid; Astrocytes; Astrocytes - cytology; Astrocytes - pathology; Biology; Bone cancer; Chicken pox; Chronic pain; Complications and side effects; Cytokines; Disease Models, Animal; Dorsal horn; Electrophysiology - methods; Gene Expression Regulation; Glutamate receptors; Glutamic acid receptors; Growth factors; Herpes zoster; Herpes Zoster - pathology; Herpesvirus 3, Human - metabolism; Hyperalgesia - pathology; Infection; Infections; Inflammation; Inhibitors; Interleukin-1beta - metabolism; Interleukins; Male; Medicine; Microglia; Microscopy, Fluorescence - methods; Minocycline; N-Methyl-D-aspartic acid receptors; Neuralgia; Neuralgia - pathology; Neuropathy; Nitric oxide; Nitric Oxide - metabolism; Nitric-oxide synthase; Pain; Pain perception; Phosphorylation; Prostate cancer; Protein expression; Quality of life; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - metabolism; Rheumatoid arthritis; Rheumatology; Rodents; Spinal cord; Studies; Time Factors; Tumor necrosis factor-TNF; Varicella; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023059

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and "NO-Astrocyte-Cytokine-NMDAR-Neuron" pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN.