The Relationship of Cyanocobalamin and Cyanocobalamin+Morphine Effects with Thrombospondin 4 (TSP 4) Tissue Levels in Rat Neuropathic Pain Model
Project no. 20111 · Status: Kapanmış · 2018
Summary
It can benefit to use drugs in combination in the treatment of neuropathic pain due to insufficient effectiveness and side effects. The importance of thrombospondin 4 (TSP4), which has increased expression in the spinal cord in peripheral nerve injury, has been demonstrated in neuropathic pain, however, there are few studies showing its relationship with drugs used in neuropathic pain treatment. In our study, the effects of cyanocobalamin and morphine, alone and in combination, on pain thresholds and spinal cord TSP4 expression in rats with neuropathy were investigated. Wistar rats were administered intraperitoneal cyanocobalamin (5-10 mg/kg/day) or saline (5 ml/kg/day) preoperatively for 15 days. Saline administration was continued to control, sham and neuropathic pain groups, while neuropathic pain treatment groups were administered 2.5-5 mg/kg/day morphine, 5-10 mg/kg/day cyanocobalamin and 5 mg/kg/day morphine+10 mg/kg/day cyanocobalamine for 4 and 14 days postoperatively. Pain thresholds measured by aesthesiometer, analgesimeter and plantar test. Spinal cord TSP4 expressions were evaluated on the postoperative 4th and 14th days, and TSP4 immunoreactivity (only in high-dose groups) on the postoperative 14th day. On the 4th postoperative day, pain thresholds decreased in three tests, while TSP4 expression increased in the drug-free neuropathy group. On the 14th day, the decrease in esthesiometer and analgesimeter persisted even though TSP4 expression returned to sham measures. Of the drug-treated neuropathic groups, cyanocobalamin and low-dose morphine did not increase pain thresholds, while high-dose morphine only improved the thresholds measured in the aesthesiometer and the combination in all tests. While TSP4 expression and immunreactivity increased with cyanocobalamin and morphine, the amount of this increase was less in combination. Our findings show that the increase in spinal TSP4 expression accompanying the decrease in pain thresholds is in the early postoperative period. The increase of the TSP4 detected with cyanocobalamin suggests that TSP4 may mediate the regenerative effects of B12 vitamins and the absence of a prominent analgesia with morphine attributed to the development of tolerance. The co-administration of the two drugs together with increased pain thresholds and less TSP4 expression/reactivity demonstrated that cyanocobalamin is improved the antinociceptive effect of morphine. Keywords: Thrombospondin 4; Neuropathic Pain; Cyanocobalamin; Morphine.