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

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 mechanicallyinduced
pain remains unchanged.