| Popis: |
Objective To observe the changes in opioid induced hyperalgesia (OIH) after subcutaneous administration of dexmedetomidine, and explore the corresponding mechanism. Methods A hundred and thirty male SD rats were randomly divided into 5 groups (26 each): saline group (NS group), 5 times of subcutaneous injection of saline 1ml; fentanyl group (F group), subcutaneous injection of saline once, and 4 times injection of fentanyl 60μg/kg; dexmedetomidine + fentanyl mixture group (DF1, DF2 and DF3 group), hypodermic dexmedetomidine once with 12.5μg/kg, 25μg/kg and 50μg/kg, respectively, and then 4 times injection of fentanyl 60μg/kg, with an interval of 15min. Rats in each group were undergone the tests of tail flick threshold (TFT) and paw withdrawal latency (PWL) 30 minutes before injection and 2, 3, 4h and 1 to 5 days after injection. Twenty rats were randomly sacrificed from each group one day after drug administration to obtain the inflated spinal lumbar region. Eight samples were used to determine the expression of alpha-2A adrenergic-receptor (α2A-AR) and inducible nitric oxide synthase (iNOS) by Western blotting, 4 were measured the expression of substance P by ELISA, and 8 were used to observe the expression of astrocytes and microglia markers glial fibrillary acidic protein (GFAP) and Iba-1 by immunofluorescence. Results The behavioral results showed that the TFT and PWL were higher at 2h to 4h after injection in F group and DF groups than in NS group, but were lower at 1 to 3 days in F group and DF1 group than in NS group, the most significant difference appeared in the 1st day and returned to the NS level at the 4th day, while no statistical difference existed when compared between NS group with DF2 and DF3 groups at 1 to 5 days. Western blotting showed that compared with NS group, the expression of α2A-AR decreased and iNOS increased in F and DF1 groups;compared with F group, the expression of α2A-AR increased and iNOS decreased in DF2 and DF3 groups; ELISA results showed that compared with the F group, the expression of substance P decreased in the three DF groups; immunofluorescence showed that the number of GFAP and Iba-1 positive cells were higher in F group than in NS and three DF groups. Conclusion Dexmedetomidine can reduce fentanyl-induced hyperalgesia by promoting α2A-AR expression, inhibiting the activation of astrocytes and microglia, thus reducing the expression of iNOS and substance P. DOI: 10.11855/j.issn.0577-7402.2018.12.06 |
