Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological
mechanisms are unknown, and the therapy is unresolved. Since the involvement of interleukin-1
(IL-1) has been described in stress and inflammatory pain but no data are available
regarding stress-induced pain, we studied its role in a chronic restraint stress (CRS)
mouse model. Female and male C57Bl/6J wild-type (WT) and IL-1αβ-deficient (knock-out:
IL-1 KO) mice were exposed to 6 h of immobilization/day for 4 weeks. Mechanonociception,
cold tolerance, behavioral alterations, relative thymus/adrenal gland weights, microglia
ionized calcium-binding adaptor molecule 1 (IBA1) and astrocyte glial fibrillary acidic
protein (GFAP) integrated density, number and morphological transformation in pain-related
brain regions were determined. CRS induced 15–20% mechanical hyperalgesia after 2
weeks in WT mice in both sexes, which was significantly reduced in female but not
in male IL-1 KOs. Increased IBA1+ integrated density in the central nucleus of amygdala,
primary somatosensory cortex hind limb representation part, hippocampus cornu ammonis
area 3 (CA3) and periaqueductal gray matter (PAG) was present, accompanied by a cell
number increase in IBA1+ microglia in stressed female WTs but not in IL-1 KOs. CRS
induced morphological changes of GFAP+ astrocytes in WT but not in KO mice. Stress
evoked cold hypersensitivity in the stressed animals. Anxiety and depression-like
behaviors, thymus and adrenal gland weight changes were detectable in all groups after
2 but not 4 weeks of CRS due to adaptation. Thus, IL-1 mediates chronic stress-induced
hyperalgesia in female mice, without other major behavioral alterations, suggesting
the analgesic potentials of IL-1 in blocking drugs in stress-related pain syndromes.
