Objective To investigate whether the peri pheral administration of amitri ptyl ine and bupivacaine produces anti-hyperalgesic effect and to screen the neurotoxicological effect on sciatic nerve blockade in a rat model of neuropathic pain. Methods Twenty-four adult male SD rats [weighing (200 ± 20) g] were made the models of chronic constriction injury (CCI) and randomly divided into 3 groups (n=8) 5 days after operation: group A (amitriptyl ine), group B (bupivacaine) and group C (normal sal ine). 0.5 mL 0.5% amitriptyl ine, 0.5% bupivacaine or normal sal ine were given in group A, group B, and group C, respectively through implanted cannulas after 5, 7 and 9 days of CCI once a day for successive 3 days. The motor function was measured before administration and 1, 2, 4, 8, 12 and 24 hours after every administration. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured before administration and 1, 3, 5 and 7 days after the third administration. The operated sciatic nerve samples were obtained for neuropathological examination under l ight microscope. Results Twenty-four CCI rats were all survival without infection, palsy and catheter fall ing off. Compared with group C, the rats of group A and group B both produced significant ambulation deficits after every administration (P lt; 0.05). The ambulation deficits lasted 2 hours (group B) and 8 hours (group A) respectively. But the ambulation deficits of CCI rats were all reversible. The MWT and TWL of group A 1 and 3 days after the third administration increased when compared with those before administration and 5 and 7 days after the third administration, and when compared with group B and group C (P lt; 0.05). There was no significant difference (P gt; 0.05) in l ight microscopic neuropathological examination among three groups. Epineurial tissue and endoneurium tissue integrity, tidy arrangement of fibers, less inflammatory cell and no marked degeneration of myel inated fibers were observed. Conclusion Repeated sciatic nerve blockade with 0.5% amitriptyl ine has peripheral anti-hyperalgesic effects on neuropathic pain of rats. No morphological evidence of neurotoxicity in the sciatic nerve of rats is observed in 0.5% amitriptyl ine.
Objective To investigate whether the peri pheral administration of amitri ptyl ine produces antihyperalgesiceffect following the chronic constriction injury (CCI) of the sciatic nerve in rats. Methods Forty-eight maleCCI 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 Aip. 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 sal ine, and 2.5, 5.0, 10.0, 15.9 mmol/L amitriptyl ine respectively through implanted cannulas on the 7th day after operation. In the group Aip, amitriptyl ine (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 fall ing off. The rats of group A2.5, group NS and group Aip didn’t produce ambulation deficits. There were no significant difference in these 3 groups (P gt; 0.05). However compared with group A2.5, group NS and group Aip, the rats of group A5, group A10, group A15.9 all produced significant ambulation deficits (P lt; 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 amitriptyl ine increased when conpared with group NS, group Aip and those of before injection (P lt; 0.05). Sciatic nerve blockade with amitriptyl ine 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 gt; 0.05). There were no significant difference between group NS and group Aip (P gt; 0.05). Conclusion The peri pheral anti-hyperalgesic effects can be found in sciatic nerve blockade of amitri ptyl ine on CCI rats. And this effect of amitri ptyl ine has concentration dependent and ceil ing effect. Amitri ptyl ine of 5.0-15.9 mmol/L can produce significantambulation deficits which are reversible.