Pharmacological characteristics of the hind paw weight bearing difference induced by chronic constriction injury of the sciatic nerve in rats.
OBJECTIVE
We examined the possible involvement of spontaneous on-going pain in the rat chronic constriction injury (CCI) model of neuropathic pain.


METHODS
The development of weight bearing deficit, as an index of spontaneous on-going pain, was investigated in comparison to that of mechanical allodynia in CCI rats. We also examined the effects of morphine and a gabapentin analogue (1S, 3R)-3-methyl-gabapentin (3-M-gabapentin) on both the CCI-induced weight bearing deficit and mechanical allodynia.


RESULTS
Rats with CCI demonstrated a significant reduction in weight bearing of the injured limb with a peak at a week post-operation, which was followed by a gradual recovery for over 7 weeks. The time course of development and recovery of CCI-induced weight bearing deficit appeared to follow that of foot deformation of the affected hind limb. CCI also evoked mechanical allodynia that was fully developed on a week post-operation, but showed no recovery for at least 8 weeks. 3-M-gabapentin significantly inhibited CCI-induced mechanical allodynia, but not weight bearing deficit, at 100 mg/kg p.o. Likewise, morphine was without significant effect on CCI-induced weight bearing deficit at the dose (3 mg/kg, s.c.) that could almost completely inhibit mechanical allodynia, whereas it inhibited both mechanical allodynia and weight bearing deficit at 6 mg/kg, s.c.


CONCLUSIONS
The present findings suggest that CCI-induced weight bearing deficit is not a consequence of mechanical allodynia, but is attributable to spontaneous on-going pain. The rat CCI model of neuropathic pain thus represents both spontaneous on-going pain and mechanical allodynia.
Nakazato-Imasato
Etsuko
E
Discovery Research, Nagoya Laboratories, Pfizer Global Research and Development, 5-2 Taketoyo, Chita-gun, Aichi 470-2393, Japan.
Kurebayashi
Yoichi
Y
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D006614:Hindlimb / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries*; D016474:Weight-Bearing
C420103:3-methylgabapentin; D000085:Acetates; D009020:Morphine