Chronic Social Stress Time-Dependently Affects Neuropathic Pain-Related Cold Allodynia and Leads to Altered Expression of Spinal Biochemical Mediators

Abstract

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.

The combination of postnatal maternal separation and social stress in young adulthood does not lead to enhanced inflammatory pain sensitivity and depression-related behavior in rats

“…The present study confirms prior results [ 10 , 51 ] as we do not see differences in thermal and mechanical sensitivity between any of the groups before inflammation. However the measurement of noxious sensitivity during periods of ongoing inflammation may generate misleading results.…”

“…Interestingly, the MS group displayed decreased mechanical thresholds at day 21 after CFA injection. A similar shift from analgesia in the early phase to hyperalgesia in the late phase was previously observed around day 21 [ 51 ]. In that particular study, SS rats displayed an enhanced cold allodynia at day 28 after chronic constriction injury (CCI) while being less sensitive shortly after CCI.…”

“…The lack of difference between the CON and SS groups before and throughout the SS period is surprising but could be related to the timing of the SS. Indeed, SS performed during adolescence has been shown to cause lasting alterations of behavioral [ 51 ] and neuroendocrine [ 27 ] features. However, in our experiments rats underwent SS during the late adolescence/beginning of adulthood, thus possibly after the high adolescence-related vulnerability window and consequently may have displayed lower alterations of their HPA axis.…”

“…Spinal NGF has been shown to mediate neuronal plasticity involved in visceral hypersensitivity [ 100 ]. Also, socially stressed rats undergoing CCI displayed higher NGF levels and enhanced pain sensitivity than rats only undergoing CCI [ 51 ]. In our hands, MS and SS only had a tendency to increase NGF mRNA levels after 21 days of inflammation.…”

Social dynamics modeling of chrono-nutrition

“…In our work, we include the two concepts of micro-inequities and micro-affirmations acting in opposite directions, representing two manifestations of this bias [28]. Since chronic stress facilitates the inflammatory action of bacteria [29], this suggests the importance of these psychological biases in influencing nodes’ or clusters’ behaviors. As well as considering the gut similarity, we also include the concept of homophily, namely the principle for which similarity breeds connection [30–32], as a similarity measure depending on interactions between nodes.…”