ORIGINAL PAPER Microglial activation in different models of peripheral nerve injury of the rat Stanislava Jergova ´ Æ Da ´s ˇa C ˇ ı ´z ˇkova ´ Received: 20 November 2006 / Accepted: 18 April 2007 / Published online: 15 May 2007 Ó Springer Science+Business Media B.V. 2007 Abstract Pain and pain modulation has been viewed as being mediated entirely by neurons. However, new research implicates spinal cord glia as key players in the creation and maintenance of pathological pain. Sciatic nerve lesions are one of the most commonly studied pain- related injuries. In our study we aimed to characterize changes in microglial activation in the rat spinal cord after axotomy and chronic constriction injury of the sciatic nerve and to evaluate this activation in regard to pain behavior in injured and control groups of rats. Microglial activation was observed at ipsilateral side of lumbar spinal cord in all experimental groups. There were slight differences in the level and extent of microglial activation between nerve injury models used, however, differences were clear between nerve-injured and sham animals in accordance with different level of pain behavior in these groups. It is known that activated microglia release various chemical mediators that can excite pain-responsive neurons. Robust microglial activation observed in present study could therefore contribute to pathological pain states observed following nerve injury. Keywords Peripheral nerve injury Á Neuropathic pain Á Allodynia Á Microglia Introduction A number of rat peripheral neuropathy models have been developed to simulate human neuropathic pain conditions. Sciatic nerve lesions are one of the most commonly studied injuries. The most obvious form of neuropathy is complete transection of the peripheral nerve, where neuroma at the site of injury and dorsal root ganglion proximal to the trauma are the source of spontaneous ectopic activity, resulted in development of abnormal pain sensations (Wall and Devor 1983). A commonly used partial nerve injury technique is the chronic constriction injury (CCI), devel- oped in rat by Bennett and Xie (Bennett and Xie 1988). In this model the sciatic nerve is loosely ligated with four chromic gut sutures and animals develop spontaneous pain- related behavior, allodynia and hyperalgesia to thermal and mechanical stimuli. Significance of the role of glial cells in the pathology of the central nervous system (CNS) is changing in recent years. Glial cells were thought to be passive cells with weak responses to synaptic activation (Haydon 2001). However, growing body of evidences implicates spinal cord glia not only as supporting cells for CNS neurons but also as an important modulator of neuronal functions under physiological and pathophysiological conditions (Watkins et al. 2001a; Watkins et al. 2001b). Glial cells are well positioned to influence neuronal functioning as they encapsulating neurons and express receptors for many neurotransmitters and transporters (Bruce-Keller 1999; Kommers et al. 1998; Palma et al. 1997). Microglia represent 5–10% of glia in CNS (Kreutzberg 1996; Stoll and Jander 1999). In adults, microglia are distributed throughout CNS and have a small soma bearing thin and branched processes under normal conditions. Microglial cells act as sensors for a range of stimuli that threaten physiological homeostasis, including CNS trauma, ischemia and infection. Activation of microglia by one or more of these stimuli results in progressive series of changes in microglial cells morphology, gene expression, S. Jergova ´(&) Á D. C ˇ ı ´z ˇkova ´ Institute of Neurobiology, Slovak Academy of Sciences, 04001 Kosice, Slovak Republic e-mail: jergova@saske.sk 123 J Mol Hist (2007) 38:245–251 DOI 10.1007/s10735-007-9094-5