Activation of spinal P2X7 receptor and analgesic effect of tramadol on neuropathic pain in rats / 医学研究生学报

ABSTRACT

Objective The mechanisms underlying neuropathic pain are complicated and the clinical effect of analgesia therap on this condition is not quite satisfactory.In this study, we observed the analgesic effects of the different doses of tramadol (T ) on neuropathic pain in rats and explored its action mechanisms . Mehtods The model of chronic sciatic nerve constriction injury (CC)I was established in male SD rats.The rats were randomly divided into five groups , sham operation ,CCI model control, low-dose T, mediumdose T, and high-dose T ,those in the latter three groups injected intraperitoneally with T at 5 , 15,and 25mg /kg qd ,respectively ,from the 7th to the 14th day after modeling.The mechanical and thermal pain thresholds of the nerve -injured hindleg were measured pre-operatively and at1 ,5 , 7, 10, 12and 14 days post-operatively.At 14 days after modeling, the expression of the P2X7receptor in the spinal dorsal horn was detected by immunohistochemistry and Western blot . Results At 5, 7,10 , 12 and 14 days after modeling,the mechanical pain threshold values were significantly decreased in the rats of the CCI model control group ([34.97±3.86 ],[34.06 ±3.79], [ 33.27±3.65], [29.03±3 . 54], and [17.90±2.34] g) and high-dose Tgroup([ 34.87±3.85], [33.47±3.66],[34 .50±3. 78 ], [29.43±3.64], and [18.63±2.42] g) as compared with the animals of the sham operation group ([39.73±5.55],[39.50±5.51], [40.97±5. 58], [41.87±5.60], and [42.97±6.75] g) (all P<0.01), and so were the thermal pain threshold valuesin the CCI model control group ([35 .21±3.94], [35.16±3.80], [29.74±2. 76], [ 20. 47±2.16], and[12.08±1.48] s) and high -dose T group ([35.76±3.76], [33.27±3.52], [31.22±3.05], [19.41±2.08], and [10.35±1.34] s) in comparison with the shamoperation group ([39.69±4.86], [39.21±4.82], [39.42±5.08], [41.17±4.88], and [42.53±5.12] s) (all P<0. 01 ).The number of the P2X7receptor positive cells and the ROD value of the P 2X7 receptor protein in the spinal dorsal horn were remarkably higher in the CCI model control than in the sham operation , low-dose T and medium-dose T groups (all P<0.01). Conclusion Intraperitoneal injection of low-dose tramadol has an analgesic effect on neuropathic pain in rats , which may be related to its decreasing effect on theexpression of the P2X7 receptor in the spinal dorsal horn.