18. Repeated morphine enhances peripheral nerve injury-induced allodynia via central immune mechanisms

Glial activation occurs after morphine and peripheral nerve injury alone, but the behavioral and molecular impact in tandem is unknown. We predicted that sciatic chronic constriction injury (CCI)-allodynia would be enhanced by subsequent repeated morphine, in a Toll-like Receptor 4 [TLR4]-dependent fashion. Mild (1 sciatic constriction) and classic (4 sciatic constrictions) CCI was performed on male Sprague Dawley (SD) and Fischer 344 (F344) rats, respectively. Beginning 10–14 days after CCI surgery, s.c. morphine (5 mg/kg or equivolume saline b.i.d.) was administered for 5 consecutive days. This morphine protocol potentiated the magnitude of mild CCI-induced allodynia (von Frey test) in SD rats ( n  = 10/group; p n  = 6/group; p n  = 6/group; p n  = 4/group; p n  = 4/group; p