PPADS

C57BL/6J (male, 20-25 g, chronic constriction injury of sciatic nerve)^[1]

6.25-25 mg/kg (chronic administration); 25 mg/kg (acute administration)

i.p.; once daily, 11 days (chronic); single dose (acute, day 3 or 14 post-injury)

Dose-dependently reduced thermal hyperalgesia and mechanical allodynia.
Completely abolished both hypersensitivity and restored physiological thresholds at 25 mg/kg (chronic).
Reduced overexpression of IL-1β mRNA and protein in ipsilateral sciatic nerve, L4-L6 dorsal root ganglia, and L4-L6 spinal cord dorsal horn at 25 mg/kg (chronic).
Reduced IL-6 mRNA overexpression in ipsilateral sciatic nerve (day 14 post-injury only) at 25 mg/kg (chronic).
Normalized increased nNOS and iNOS protein levels in ipsilateral sciatic nerve, L4-L6 dorsal root ganglia, and L4-L6 spinal cord dorsal horn at 25 mg/kg (chronic).
Abolished doubled nNOS protein level in contralateral thalamus relative to ipsilateral thalamus at 25 mg/kg (chronic).
Reversed NF-κB activation in ipsilateral sciatic nerve at 25 mg/kg (chronic).
Restored reduced P0 myelin protein mRNA levels in ipsilateral sciatic nerve to physiological levels at 25 mg/kg (chronic).
Reversed mechanical allodynia at 1 hour post-administration (effect absent by 24 hours) without modifying thermal hyperalgesia when given at day 3 post-injury (acute 25 mg/kg).
Produced identical effects on mechanical allodynia and thermal hyperalgesia as day 3 acute dose when given at day 14 post-injury (acute 25 mg/kg).