Differential activation of spinal cord glial cells in murine models of neuropathic and cancer pain

Abstract

Activation of spinal cord microglia and astrocytes is a common phenomenon in nerve injury pain models and is thought to exacerbate pain perception. Following a nerve injury, a transient increase in the presence of microglia takes place while the increased numbers of astrocytes stay elevated for an extended period of time. It has been proposed that activated microglia are crucial for the development of neuropathic pain and that they lead to activation of astrocytes which then play a role in maintaining the long term pathological pain sensation. In the present report, we examined the time course of spinal cord glial activation in three different murine pain models to investigate if microglial activation is a general prerequisite for astrocyte activation in pain models. We found that two different types of cancer induced pain resulted in severe spinal astrogliosis without activation of microglia. In contrast, sciatic nerve injury led to a transient activation of microglia and sustained astrogliosis. These results show that development of hypersensitivity and astrocyte activation in pain models can take place independent of microglial activation.

Spinal Astrocytes as Therapeutic Targets for Pathological Pain

“…It has been shown using OX-42, a microglial activation marker, and GFAP, an astrocytic activation marker, that early spinal microglial activation and delayed spinal astrocytic activation follow nerve injury/ inflammation (9,11,12). Even after microglial activation begins to decrease, astrocytic activation persists, as does neuropathic pain (13). This temporal pattern is further confirmed by sequential activation of mitogen-activated protein kinase (MAPK) / extracellular signal-regulated kinase (ERK) in microglia and then in astrocytes following spinal nerve ligation (SNL) (14).…”

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

“…The concept of "functional islands of synapses" highlights the vital roles astrocytes play in the modulation of neuronal function by synchronizing neuronal firing and coordinating synaptic networks [41] . A study using mice demonstrated that the activation of astrocytes, but not microglia, was a prerequisite in two types of cancer-induced pain models [42] . Therefore, reactive astrocytes play a crucial role in BCP.…”

Microarchitectural adaptations in aging and osteoarthrotic subchondral bone issues

“…Micro-CT in vitro scanning has been widely used for bone samples obtained from all sizes of animal, such as mouse [2,[75][76][77], rat [175], guinea pig [44], rabbit [52,149], dog [28,46,85,101,102], pig [106,107] sheep [7,37], and human [29,51,[64][65][66][67]. In vivo micro-CT imaging can now also be applied to all sizes of animals depending on the location to be scanned.…”