Effect of astaxanthin on neuropathic pain in rats and role of spinal heme oxygenase-1 / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of astaxanthin on neuropathic pain in rats and the role of spinal heme oxygenase-1 (HO-1).Methods:Seventy-two SPF-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, in which intrathecal catheters were successfully implanted, were divided into 6 groups ( n=12 each) by a random number table method: blank control group (group C), sham operation group (Sham group), neuropathic pain (NP) group, NP plus dimethyl sulfoxide (DMSO) group (NP + DMSO group), NP plus astaxanthin group (NP + AST group) and NP plus zinc protoporphyrin plus astaxanthin group (NP+ ZnPP+ AST group). NP was induced by chronic constriction injury in anesthetized rats.In Sham group, the sciatic nerve was only isolated without ligation.At 5 days after establishing the model, 0.5% DMSO 10 μl was intrathecally injected in NP+ DMSO group, astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ AST group, HO-1 inhibitor zinc protoporphyrin 24 μg (dissolved in 10 μl DMSO) was intrathecally injected, and 3 h later astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ ZnPP+ AST group.Injection was given once a day for 10 consecutive days in the 3 groups mentioned above.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 3, 7 and 14 days after establishing the model.The rats were sacrificed at 14 days after establishing the model, and the L 4-6 lumbar segments of the spinal cord were removed for determination of the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD) and glutathione peroxidase (GHS-PX)(by enzyme-linked immunosorbent assay) and expression of HO-1 (by Western blot). Results:Compared with group C and group Sham, the MWT was significantly decreased and TWL was shortened at each time point after establishing the model, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was up-regulated in the other four groups, the SOD and GSH-PX contents were significantly decreased in NP group, NP+ DMSO group and NP+ ZnPP+ AST group, and the SOD and GSH-PX contents were significantly increased in NP+ AST group ( P<0.05). Compared with NP group, the MWT was significantly increased and TWL was prolonged at 7 and 14 days after establishing the model, the contents of TNF-α and IL-1β were decreased, and the expression of HO-1 was up-regulated in NP+ AST group, the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05), and no significant change was found in the parameters mentioned above in NP+ DMSO group ( P>0.05). Compared with NP+ AST group, the MWT was significantly decreased and TWL was shortened at 7 and 14 days after establishing the model, the contents of SOD and GSH-PX were decreased, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05). Conclusion:Astaxanthin can reduce NP in rats, and the mechanism is related to up-regulating the expression of HO-1 in the spinal cord and inhibiting oxidative stress and inflammatory responses.