Expression Of Vanilloid Receptor In Spinal Cord And Dorsal Ganglion Of Arthritic Rats With Morphine Tolerance

Objective:Opioids are one of the most effective analgesics for treating many forms of chronic pain. Besides the known side effects, long term using of opioids frequently developed to opoid tolerance, the patients need more doses to relieve pain and could appear abnormal hyperalgesia. Though there are so many relavent articles on the research about the mechanism of opoid tolerance, the cellular and molecular mechanism of opoid tolerance is still not known well yet. The common causes of chronic pain is the inflammation, but previous studies seldom concerned about the mechanisms of the relationship between inflammation with opioids tolerance. So we use the chronic inflammatory rat model to investigate the alteration of vanilloid receptor in the spinal dorsal horn and dorsal root ganglion after administration of morphine intrathecally, and try to explain the mechanism of motphine tolerance, thereby we wish to find a new way of clinic care.Methods:Forty adult SD rats weighting 250±20g were randomal divided into five groups with 8 animals in each group. Group A:blank control group, the rats were injected normal saline 50ul into ankle joint cavity,3 days later administered intrathecally normal saline lOul, twice daily for 7 days; group B:arthritic control group, the rats were injected CFA 50ul into ankle joint cavity,3 days later administered intrathecally normal saline lOul, twice daily for 7 days; group C: arthritic morphine 10μg group, the rats were injected CFA 50ul into ankle joint cavity, 3 days later administered intrathecally morphine lOug; group D:arthritic morphine 20μg group, the rats were injected CFA 50ul into ankle joint cavity,3 days later administered intrathecally morphine 20ug; group E:morphine control group, the rats were injected normal saline 50ul into ankle joint cavity,3 days later administered intrathecally morphine 20ug, twice daily for 7 days. To evaluate the behavioral changes, paw withdrawal mechanical threshold (PWT) and paw withdrawl thermal latency (PWL) were measured every other day. Immunofluorescent marking technology and computer image analysis system were used to observe the changes of expression of TRPV-1 in the spinal dorsal horn and dorsal root ganglion. Results:1. The paw withdrawal latency of group B-D was shortened three days after injection of CFA; Compared with the 3rd day after CFA injection and group B, the withdrawal latency of group C-D increased at the 4th day after CFA, and began to decrease at the 8th day, and stayed at low level at the 10th day; the withdrawal latency of group A did not change at the 7th day after injection of morphine; the withdrawal latency of group E decreased at the 5th and 7th day after medication, compared with the basal line.2. At the 7th day after intrathecal morphine injection, compared with group A, the expression of TRPV-1 were significantly increased in spinal dorsal horn and dorsal root ganglion in group B-E; compared with group B, it increased in group C-E; compared with E, it increased in group D.Conclusion:1. On the basis of inflammation, the morphine tolerance rat model with chronic arthritis can be produced with morphine intrathecally injection for 7days.2. Chronic morphine using may be related to upregulation of vanilloid receptor in the spinal dorsal horn and dorsal root ganglion. The upregulation of vanilloid receptor may contribute to one of the molecular mechanism of opoid tolerance.Innovation:1.The morphine tolerant rat model with chronic arthritis is more comparable with the clinical condition than the previous models.2. Investigation the alteration of vanilloid receptor provides a new way to explain the mechanism of morphine tolerance.