The lumbar spinal cord glial cells actively modulate subcutaneous formalin induced hyperalgesia in the rat

• Published in: Neuroscience research Vol. 55; no. 4; pp. 442 - 450
• Main Authors: Qin, Ming, Wang, Jing-Jie, Cao, Rong, Zhang, Hui, Duan, Li, Gao, Bei, Xiong, Ying-Fei, Chen, Liang-Wei, Rao, Zhi-Ren
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01-08-2006
• Subjects: Afferent Pathways - drug effects; Afferent Pathways - physiology; Animals; Astrocytes - metabolism; Astrocytes - ultrastructure; Biomarkers - metabolism; Carbenoxolone - pharmacology; CD11b Antigen; Cell Communication - drug effects; Cell Communication - physiology; Citrates - pharmacology; Connexins - metabolism; Disease Models, Animal; Formalin; Gap Junctions - drug effects; Gap Junctions - metabolism; Gap Junctions - ultrastructure; Glial cell; Glial Fibrillary Acidic Protein - metabolism; Glial–neuronal interaction; Hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - physiopathology; Male; Microglia - metabolism; Microglia - ultrastructure; Nerve Tissue Proteins - metabolism; Neuron; Nociceptors - drug effects; Nociceptors - physiology; Nuclear Proteins - metabolism; Pain - chemically induced; Pain - physiopathology; Pain Measurement - drug effects; Posterior Horn Cells - metabolism; Posterior Horn Cells - ultrastructure; Proto-Oncogene Proteins c-fos - metabolism; Rat; Rats; Rats, Sprague-Dawley; Glial–neuronal interaction; Formalin; Glial cell; Neuron; Rat; Hyperalgesia
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2006.04.017

We investigated the response and relationship of glial cells and neurons in lumbar spinal cord to hyperalgesia induced by the unilateral subcutaneous formalin injection into the hindpaw of rats. It was demonstrated that Fos/NeuN immunoreactive (-IR) neurons, glial fibrillary acidic protein (GFAP)-IR astrocytes and OX42-IR microglia were distributed in dorsal horn of lumbar spinal cord, predominantly in the superficial layer. In the time-course studies, GFAP-IR astrocytes were firstly detected, OX42-IR microglia were sequentially observed, Fos/NeuN-IR neurons were found slightly late. Immunoelectron microscopy studies established that many heterotypic gap junctions (HGJs), which consisting of Cx43-IR astrocytic process on one side and Cx32-IR dendrite on the other side, were present in superficial layer of dorsal horn. Ninety-one HGJs were found in 100 areas of experimental rats and occupied 91%, while only 39% HGJs were found in control rats. In experimental rats pretreated with intrathecal (i.t.) application of the carbenoxolone (a gap junction blocker) or fluorocitrate (a glial metabolic inhibitor), the paw withdrawal thermal latency was prolonged than those application of the sterile saline (i.t.). It suggests that spinal cord glial cells may play an important role for modulation of hyperalgesia induced by noxious stimuli through HGJs which located between astrocytes and neurons.