[Peripheral anti-hyperalgesic effect and neurotoxicologic screening of amitriptyline and bupivacaine on sciatic nerve blockade chronically on neuropathic pain in rats].

Objective: To investigate whether the peripheral administration of amitriptyline 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 (amitriptyline), group B (bupivacaine) and group C (normal saline). 0.5 mL 0.5% amitriptyline, 0.5% bupivacaine or normal saline 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 light microscope.

Results: Twenty-four CCI rats were all survival without infection, palsy and catheter falling off. Compared with group C, the rats of group A and group B both produced significant ambulation deficits after every administration (P < 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 < 0.05). There was no significant difference (P > 0.05) in light microscopic neuropathological examination among three groups. Epineurial tissue and endoneurium tissue integrity, tidy arrangement of fibers, less inflammatory cell and no marked degeneration of myelinated fibers were observed.

Conclusion: Repeated sciatic nerve blockade with 0.5% amitriptyline 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% amitriptyline.