Objective: To investigate whether the peripheral administration of amitriptyline produces antihyperalgesic effect following the chronic constriction injury (CCI) of the sciatic nerve in rats.
Methods: Forty-eight male CCI rats weighing (220 +/- 20) g were randomly divided into 6 groups (n = 8): group NS, group A2.5, group A5, group A10, group A15.9 and group A(ip). In the group NS, group A2.5, group A5, group A10 and group A15.9, sciatic nerve blockade was locally performed with 0.5 mL normal saline, and 2.5, 5.0, 10.0, 15.9 mmol/L amitriptyline respectively through implanted cannulas on the 7th day after operation. In the group A(ip), amitriptyline (2.5 mg) was administered by intraperitoneal injection. The mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL) and motor function were measured before and 1, 2, 4, 8, 12, 24 and 48 hours after sciatic nerve blockade.
Results: Forty-eight CCI rats were all survival without infection, palsy and catheter falling off. The rats of group A2.5, group NS and group A(ip) didn't produce ambulation deficits. There were no significant difference in these 3 groups (P > 0.05). However compared with group A2.5, group NS and group A(ip), the rats of group A5, group A10, group A15.9 all produced significant ambulation deficits (P < 0.05). The ambulation deficits lasted 2 hours (group A5), 4 hours (group A10), 8 hours (group A15.9) respectively. But the ambulation deficits of CCI rats were all reversible. The MWT and TWL of groups with local injection of amitriptyline increased when compared with group NS, group A(ip) and those of before injection (P < 0.05). Sciatic nerve blockade with amitriptyline significantly suppressed mechanical hyperalgesia and thermal hyperalgesia in neuropathic rats. The peripheral anti-hyperalgesic effects lasted 2 hours (A2.5 group), 4 hours (group A5), 24 hours (group A10), 24 hours (group A15.9) respectively. But there were no significant difference between A10 group and A15.9 group (P > 0.05). There were no significant difference between group NS and group A(ip) (P > 0.05).
Conclusion: The peripheral anti-hyperalgesic effects can be found in sciatic nerve blockade of amitriptyline on CCI rats. And this effect of amitriptyline has concentration dependent and ceiling effect. Amitriptyline of 5.0-15.9 mmol/L can produce significant ambulation deficits which are reversible.
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