A rat model of postthoracotomy pain: Behavioural and spinal cord NK-1 receptor assessment

Abstract

Purpose: To develop a new rat model of postthoracotomy pain for investigating its mechanisms and clarifying neurochemical changes. Methods: Male Wistar rats were randomly assigned to three groups that underwent either fourth and fifth intercostal nerve ligation, cutting of the fourth and fifth ribs, or a sham operation in which only pleura was cut. For behavioural response assessment during the following month, pinch and touch were used as mechanical stimuli, and acetone was used as a cold thermal stimulus. In addition, 125I-substance P autoradiography was used to determine neurokinin (NK) receptor density in spinal cord laminae I and II at one to six weeks after surgery. Results: In rats with nerve ligation, hypersensitivity to noxious and non-noxious stimuli continued throughout the month. The "mirror phenomenon" was observed. The lowest threshold was obtained in the dorsomedial portion of the T4 dermatome on the side of surgery. In rats with rib cutting, a lowered threshold to noxious and non-noxious stimuli was observed for two weeks. In rats with sham operations, hypersensitivity was seen only at postoperative day one. NK-I receptor density on the side of operation increased significantly in rats with nerve ligation from day seven to 28. Receptor density was highest on day 14 (22.97 ± 1.04 fmol·mg-1 tissue vs control, 16.22 ± 0.43), representing a 50% receptor excess on the side of ligation compared to the contralateral side. Conclusion: Intercostal nerve damage induces long-term postthoracotomy pain and an increase of spinal NK-I receptors in rats. This model may be useful for investigation of postthoracotomy pain.