Single Intraperitoneal Injection of Low-Dose Ketamine Pretreatment Alleviates Mechanical Hyperalgesia and Downregulates the Expression of Inflammatory Cytokines in Spinal Dorsal Horn of Rats

Abstract

Single intraperitoneal injection of low-dose ketamine pretreatment alleviates mechanical hyperalgesia and downregulates the expression of inflammatory cytokines in spinal dorsal horn of rats after skin/muscle incision and retraction. J Anesth Perioper Med 2015; 2: 236-43.Background: Various common surgeries, such as thoracotomy and inguinal hernia repair which involve essential prolonged tissue retraction, often evoke chronic postoperative pain (CPOP). They bring great pain to patients, and make the qualities of their lives lower. The concrete mechanism of CPOP has still been unclear, and lacks effective research methods. To solve this problem, a new rat model was developed, whereby skin/muscle incision and retraction (SMIR) in the medial thigh of rat evoked CPOP to simulate clinical scene. Many studies provided evidence that CPOP often is accompanied with a large number of inflammatory cytokines releasing, and these cytokines induce or facilitate inflammatory hyperalgesia. In the present study, we investigated the expression of inflammatory cytokines in a SMIR rat model and examined the effects of low-dose ketamine pretreatment. Methods: Paw withdrawal mechanical threshold (PWMT) was used to assess mechanical hyperalgesia 1 day before and 1, 3, 7, 10, 14, 21, and 28 days after a SMIR operation. Western blotting was used to investigate the expression of interleukin (IL)-1, IL-6, IL-17, and tumor necrosis factor (TNF)-α at the spinal level. Results: SMIR rats developed long-lasting mechanical hyperalgesia, companied with the upregulation of inflammatory cytokines at the spinal level. A single intraperitoneal injection of low-dose ketamine before SMIR surgery could alleviate mechanical hyperalgesia significantly and downregulate the expression of IL-1, IL-6, IL-17, and TNF-α at the spinal level. Conclusions: Our data suggested that the expression of IL-1, IL-6, IL-17, and TNFα at the spinal level in the rats of SMIR-induced CPOP were upregulated, and a single pre-intraperitoneal injection of low-dose ketamine could alleviate mechanical hyperalgesia and downregulate the expression of inflammatory cytokines in spinal dorsal horn. This might be a novel target for CPOP therapy.