title: Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia.
abstract: Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund's Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression. And, microglia were also significantly activated with the presence of increased Iba-1 expression. Intrathecal administration of c-fos antisense oligodeoxynucleotides (ASO) or minocycline (a specific microglia inhibitor) attenuated mechanical allodynia. Moreover, intrathecal administration of c-fos ASO significantly suppressed the activation of neurons and microglia. Interestingly, inhibition of microglia activation by minocycline significantly suppressed the activation of both neurons and microglia in spinal dorsal horn. P38 inhibitor SB203580 suppressed IL-6 production, and inhibition of IL-6 receptor (IL-6R) activation by tocilizumab suppressed Fos expression. Together, our data suggest that the presence of a "crosstalk" between activated microglia and neurons in the spinal dorsal horn, which might contribute to the stress-induced hyperactivated state, leading to an increased pain sensitivity.
authors.affiliation: Department of Spinal Cord Injury and Rehabilitation, The General Hospital of Jinan Military Command, Jinan, 250031, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Pharmacy, The Second Hospital of Shandong University, Jinan, 250031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Spinal Cord Injury and Rehabilitation, The General Hospital of Jinan Military Command, Jinan, 250031, China.
authors.forename: Qing-Xi
authors.initials: QX
authors.lastname: Meng
authors.affiliation: Department of Neurobiology, Institute of Basic Medical Sciences, Beijing, 100850, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurobiology, Institute of Basic Medical Sciences, Beijing, 100850, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Spinal Cord Injury and Rehabilitation, The General Hospital of Jinan Military Command, Jinan, 250031, China.
authors.forename: Ting-Bao
authors.initials: TB
authors.lastname: Zhao
mesh_terms: D000818:Animals; D016762:Genes, fos / Q000235:genetics; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008911:Minocycline / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D007093:Imidazoles; D015850:Interleukin-6; D011725:Pyridines; D008911:Minocycline; C093642:SB 203580