Glial cell activation in the spinal cord and dorsal root ganglia induced by surgery in mice

In rodents, surgery and/or remifentanil induce postoperative pain hypersensitivity together with glial cell activation. The same stimulus also produces long-lasting adaptative changes resulting in latent pain sensitization, substantiated after naloxone administration. Glial contribution to postoperative latent sensitization is unknown. In the incisional pain model in mice, surgery was performed under sevoflurane+remifentanil anesthesia and 21 days later, 1 mg/kg of (-) or (+) naloxone was administered subcutaneously. Mechanical thresholds (Von Frey) and glial activation were repeatedly assessed from 30 min to 21 days. We used ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) to identify glial cells in the spinal cord and dorsal root ganglia by immunohistochemistry. Postoperative hypersensitivity was present up to 10 days, but the administration of (-) but not (+) naloxone at 21 days, induced again hyperalgesia. A transient microglia/macrophage and astrocyte activation was present between 30 min and 2 days postoperatively, while increased immunoreactivity in satellite glial cells lasted 21 days. At this time point, (-) naloxone, but not (+) naloxone, increased GFAP in satellite glial cells; conversely, both naloxone steroisomers similarly increased GFAP in the spinal cord. The report shows for the first time that surgery induces long-lasting morphological changes in astrocytes and satellite cells, involving opioid and toll-like receptors, that could contribute to the development of latent pain sensitization in mice.