The activation of spinal astrocytes contributes to preoperative anxiety-induced persistent post-operative pain in a rat model of incisional pain.

Abstract

Preoperative anxiety, a clinically significant problem for many patients undergoing surgery, is associated with prolonged and exacerbated post-operative pain. To date, the mechanisms of preoperative anxiety-induced persistent post-operative pain remain unclear. The present study aimed to provide a rat model of preoperative anxiety-induced persistent post-operative pain using the single-prolonged stress (SPS) procedure to induce preoperative anxiety-like behaviours, and to explore the role of spinal astrocytes in this phenomenon. Rats were exposed to the SPS procedure to induce preoperative anxiety-like behaviours. Subsequently, acute post-operative pain was developed using a 1-cm longitudinal incision through skin and fascia of the plantar aspect of the right hindpaw. Mechanical allodynia was measured before and after the incision. Immunofluorescence assay was used to assess the expression of glial fibrillary acidic protein and the activation of astrocytes in spinal dorsal horn. The SPS performed before the incision resulted in (1) enhanced preoperative anxiety-like behaviours as revealed by the elevated plus maze tests; (2) exacerbated and prolonged mechanical allodynia that lasted for at least 28 post-operative days; and (3) activation of astrocytes in the lumbar spinal dorsal horn. The data suggest that this rat model, which could mimic the clinical persistent post-operative pain induced by preoperative anxiety, may be a useful tool to explore the mechanisms as well as effective prevention and treatment for this problem. Furthermore, spinal astrocytes activation may contribute to the development of post-operative hyperalgesia in this model.