ORIGINAL RESEARCH published: 09 May 2017 doi: 10.3389/fnbeh.2017.00070 Chronic Social Stress Time-Dependently Affects Neuropathic Pain-Related Cold Allodynia and Leads to Altered Expression of Spinal Biochemical Mediators Glenn-Marie Le Coz , Julien Genty, Fernand Anton and Ulrike Hanesch* Laboratory of Neurophysiology and Psychobiology, Institute for Health and Behavior, University of Luxembourg, Luxembourg, Luxembourg Edited by: Oliver T. Wolf, Ruhr University Bochum, Germany Reviewed by: Martin Hadamitzky, Essen University Hospital, Germany Nikita Burke, University of Calgary, Canada *Correspondence: Ulrike Hanesch ulrike.hanesch@uni.lu Received: 01 January 2017 Accepted: 07 April 2017 Published: 09 May 2017 Citation: Le Coz G-M, Genty J, Anton F and Hanesch U (2017) Chronic Social Stress Time-Dependently Affects Neuropathic Pain-Related Cold Allodynia and Leads to Altered Expression of Spinal Biochemical Mediators. Front. Behav. Neurosci. 11:70. doi: 10.3389/fnbeh.2017.00070 Clinical data have shown that chronic exposure to stress may be accompanied by an enhancement of inflammation-related pain sensitivity. In this context, little is however known on the impact of stress on neuropathic pain. In the present study we addressed this issue by combining the chronic constriction injury (CCI) model with an ongoing social stress (OSS) paradigm. Cold plate and von Frey tests were performed in 48 rats divided into four groups: OSS exposed to OSS, CCI subjected to chronic nerve constriction, OSS+CCI with a combination of neuropathy and stress and CON, a control group lacking any manipulation. While we did not observe any stress-related differences in mechanical sensitivity throughout the observation period, CCI rats were more sensitive to cold stimulation than OSS+CCI in the initial phase of neuropathy. A switch was observed at a later stage, leading to a hypersensitivity of the OSS+CCI compared to the CCI rats. At this time point we investigated the spinal mRNA expression of neuron and glia related molecules potentially involved in neuropathic pain and stress. The combination of psychosocial stress and neuropathic pain seemed to enhance glial cell activation, pro-inflammatory cytokine and neurotrophic factor mRNA levels, rather than glutamatergic transmission. Our data show that long lasting social stress may lead to time-dependent alteration of neuropathy-related cold pain sensitivity while mechanically- induced pain remains unchanged. Keywords: neuropathy, social stress, cold sensitivity, mechanical sensitivity, biochemical pathways INTRODUCTION While exposure to stress may lead to the classically described phenomenon of stress-induced analgesia (SIA, for review see Butler and Finn, 2009), increasing amounts of data suggest that it may under certain conditions also lead to an enhancement of pain, denominated as stress-induced hyperalgesia (SIH, see Jennings et al., 2014). In this context, research has laid a more pronounced emphasis on inflammatory as compared to neuropathic pain, a clinical entity that remains difficult to treat (Finnerup et al., 2010). In this context comorbidities Frontiers in Behavioral Neuroscience | www.frontiersin.org 1 May 2017 | Volume 11 | Article 70