Various forms of mild stress may exacerbate pain in patients with chronic pain disorders, though the underlying mechanism remains unclear. Astrocyte activation in the spinal dorsal horn plays a predominant role in stress and pain. The present study investigated the neuron-astrocyte interactions in the spinal dorsal horn in post-traumatic stress disorder (PTSD)-induced hyperalgesia using a single-prolonged stress (SPS) model, a Complete Freund's Adjuvant (CFA) model and an SPS + CFA model. Animals were tested for mechanical withdrawal threshold (MWT) of the paw after SPS, CFA and SPS + CFA. SPS + CFA group induced significantly increased mechanical allodynia compared with the SPS or CFA group. We tested the hypothesis that IL-1β contributes to signaling between astrocytes and neurons in stress-induced hyperalgesia (SIH). Immunohistochemical data showed that there was an upregulation of glial fibrillary acidic proteins (GFAPs, a marker of astrocyte) and Fos (a marker of neuron) in SIH. Immunohistochemical data showed specific localization of IL-1β to astrocyte, but not to microglia and neurons and a neuronal localization of the IL-1β receptor (IL-1RI) with NMDAR2B (NR2B). Enzyme immunoassay analysis showed that IL-1β release was dependent on c-Jun N-terminal kinase (JNK) activation in astrocyte. The JNK inhibitor SP600125 suppressed IL-1β release. SP600125 and IL-1RI blockade with IL-1ra resulted in a restoration of behavioral nociceptive thresholds. Our results showed that the IL-1β-dependent, JNK-regulated astrocyte-neuron signaling pathway mediated the astroglia component of pain maintenance in SIH.
Qi et al. (Thu,) studied this question.