Objective To investigate the analgesic effect of a specific p38MAPK inhibitor SB203580 in a rat model of chronic constriction injury (CCI) to sciatic nerve. Methods Male SD rats weighing 220-250 g were used in this study. The neuropathic pain model was established by CCI to sciatic nerve. The rats were anesthetized with intraperitoneal (i.p.) pentobarbital 40 mg?kg-1. Left sciatic nerve was exposed and 4 loose ligatures were placed on left sciatic nerve at 1 mm intervals with 4-0 silk suture. The animals were allowed 7 days to recover from surgery. Intrathecal (IT) SB203S80 was given through a needle inserted at L5,6 interspace. In experiment A, 40 rats wee randomly divided into 5 groups (n = 8 each): control group and 4 SBgroups (SB203580 0.1, 0.5, 2.5 and 5.0 ?g were given respectively) . Response of the hindpaw to mechanical stimulation with von Frey filament (MWT) was measured before (T0,baseline) and at 0.5, 3, 6, 12 and 24 h (T1-5) after IT SB203580 injection. In experiment B, 36 animals were randomly divided into 6 groups (n = 6 each): (1) sham operation group; (2) CCI group; (3) DMSO group; (4) SB 0.1 ?g group; (5) SB 0.5 ?g group and (6) SB 5.0 ?g group. The animals were lulled at 6h after IT SB203580 administration and L5,6 lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal horn by immuno-cytochemistry. Results The rats developed hyperalgesia after CCI and IT SB203580 administration significantly increased MWT in a dose dependent manner. The number of pCREB positive neurons in the L4,5 spinal dorsal horn was significantly increased after CCI. Interthecal administration of SB203580 0.5 or 5.0 ?g significantly inhibited the CCI-induced increase in pCREB expression. Conclusion Intrathecal administration of SB203580 can attenuate the hyperalgesia induced by CCI and inhibition of CREB phosphorylation in the spinal dorsal horn is involved in the mechanism.

AIM: To investigate the effects of hypobaric hypoxia in plateau on tear indexes and related anatomical structures in rabbits.METHODS: A total of 18 healthy New Zealand rabbits were selected and randomly divided into plateau group and control group, with 9 rabbits(18 eyes)in each group. The plateau group was housed in the Simulated Climate Cabin for Special Environment of Northwest of China, simulating hypobaric hypoxia at an altitude of 6 000 m. The control group was housed in a clean animal room with atmospheric pressure and oxygen. Changes in the tear meniscus height and non-invasive tear break-up time were detected by using RHCT-1 corneal topographer dry eye comprehensive analysis system, changes in tear secretion was measured by Schirmer Ⅰ test, before intervention and on the 3, 7 d, 2 and 4 wk. Meanwhile, the changes in tear composition before and after intervention in the plateau environment were analyzed using Raman Spectroscopy. The histopathological changes of the lower lid conjunctiva, cornea, lacrimal gland, and Hardarian gland were observed by hematoxylin-eosin(HE)staining after 4 wk of intervention, and the expression of mucin 5AC(MUC5AC)in conjunctiva was detected by immunohistochemistry.RESULTS: Compared with the control group, Schirmer Ⅰ test, tear meniscus height, first and average non-invasive tear break-up time in the plateau group decreased significantly since 3 d, and the difference was significant with the extension of observation time(P<0.05). The above indexes increased from 2 wk. After 4 wk of intervention, the protein and lipid content of the tear composition of rabbits in the plateau group increased, and the nucleic acid content decreased compared with the pre-intervention period. Compared with the control group, rabbits in the plateau group showed thickening of corneal stromal edema, an increase in the number of conjunctival cup cells, increase in the level of expression of MUC5AC, an increase in the level of expression of MUC5AC, an atrophy and flattening of cytoplasm in lacrimal epithelial cells, an enlargement of glandular lumen, and no obvious destructive changes in the Hardarian glands.CONCLUSION: Acute plateau environment can destroy the homeostasis of rabbit ocular surface, so that the tear secretion and the tear film stability decreases, but within a certain period of time, rabbits undergo compensation with the habituation to the hypobaric hypoxia environment, which can increase the tear secretion to a certain extent and restore the tear film stability.