Neuroscience Letters 569 (2014) 59–62 Contents lists available at ScienceDirect Neuroscience Letters jo ur nal ho me page: www.elsevier.com/locate/neulet Satellite glial cells in dorsal root ganglia are activated in experimental autoimmune encephalomyelitis Rebekah A. Warwick a,∗ , Craig J. Ledgerwood a , Talma Brenner b , Menachem Hanani a a Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel b Department of Neurology, and the Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel h i g h l i g h t s • Ten days post EAE induction, mice had reduced pain thresholds. • GFAP expression was increased in SGCs in DRG of 10-day EAE mice. • Coupling among SGCs was increased in DRG of 10-day EAE mice. a r t i c l e i n f o Article history: Received 12 November 2013 Received in revised form 5 March 2014 Accepted 20 March 2014 Keywords: Multiple sclerosis Experimental autoimmune encephalomyelitis Dorsal root ganglia Satellite glial cell Pain a b s t r a c t Pain is a serious and common problem with patients suffering from multiple sclerosis (MS). Very little has been done to investigate the peripheral mechanisms of pain in MS. Here we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to investigate the possible contribution of satellite glial cells (SGCs) to pain in MS. EAE mice had reduced pain thresholds 10 days after disease induction. We examined dorsal root ganglia and found increased expression of glial fibrillary acidic protein in SGCs, a marker of SGC activation, and increased coupling among SGCs, a known component of activated SGCs. Activated SGCs have previously been shown to contribute to pain in other classical neuropathic pain models, suggesting that pain in multiple sclerosis has a peripheral component. © 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system (CNS). Pain is a common problem for MS patients, with reported prevalence of between 43% and 92% [1,2], and in 23% of MS patients, pain was present even at the onset of the disease [3]. Pain in MS patients has been classified into three groups; central neuropathic pain (which includes trigeminal neu- ralgia, Lhermitte’s sign and dysesthetic pain in the extremities), musculoskeletal pain and headaches [4]. Experimental autoimmune encephalomyelitis (EAE) is the ani- mal model used for the study of MS, which shares many Abbreviations: CNS, central nervous system; CFA, complete Freund’s adjuvant; DAPI, 4,6-diamidino-2-phenylindole dihydrochloride; DRG, dorsal root ganglia; GFAP, glial fibrillary acidic protein; GFAP-IR, GFAP-immunoreactive; EAE, experi- mental autoimmune encephalomyelitis; LY, Lucifer yellow; MS, multiple sclerosis; PNS, peripheral nervous system; SGC, satellite glial cell. ∗ Corresponding author. Tel.: +972 2 5844720; fax: +972 2 5844080. E-mail address: rawarwick87@gmail.com (R.A. Warwick). pathological features of the disease, such as inflammation, demyeli- nation, and impaired locomotor activity [5,6]. A small number studies have utilised the EAE model for investigating pain in MS. Mechanical hyperalgesia and thermal cold allodynia was shown in a rat EAE model [7] and in a mouse EAE model [8]. MS is considered a CNS disease, however recent research using the EAE animal models has shown that the peripheral nervous system (PNS) is also affected. Expression of brain-derived neu- rotrophic factor (BDNF) and the cytokine, tumour necrosis factor alpha (TNF), were both significantly increased in dorsal root ganglia (DRG) of EAE models, and this increase was positively cor- related with neurological disability [9,10]. Ectopic neuronal activity originating from the sensory ganglia has long been implicated in the initiation and maintenance of chronic pain [11]. More recently, satellite glial cells (SGCs), which surround neurons in the sensory ganglia, have also been shown to contribute to pain in nerve injury and in other neuropathic pain models [12–14]. Gap junctional coupling among SGCs was found to be increased in pain models. Administration of gap junction blockers to ani- mal pain models reduced pain behaviour [12,14]; suggesting that http://dx.doi.org/10.1016/j.neulet.2014.03.033 0304-3940/© 2014 Elsevier Ireland Ltd. All rights reserved.