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.
Etsuko
E
Nakazato-Imasato
Yoichi
Y
Kurebayashi
D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D000077206:Gabapentin; D006614:Hindlimb / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009408:Nerve Compression Syndromes / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D016474:Weight-Bearing; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin