Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia.
OBJECTIVE
In the present study, we sought to develop/characterize the pain profile of a rat model of surgically induced osteoarthritis (OA).


METHODS
OA was surgically induced in male Lewis rats (200-225 g) by transection of the medial collateral ligament and medial meniscus of the femoro-tibial joint. In order to characterize the pain profile, animals were assessed for a change in hind paw weight distribution (HPWD), development of mechanical allodynia, and the presence of thermal and mechanical hyperalgesia. Rofecoxib and gabapentin were examined for their ability to decrease change in weight distribution and tactile allodynia.


RESULTS
Transection of the medial collateral ligament and medial meniscus of male Lewis rats resulted in rapid (<3 days) changes in hind paw weight bearing and the development of tactile allodynia (secondary hyperalgesia). There was, however, no appreciable effect on thermal hyperalgesia or mechanical hyperalgesia. Treatment with a single dose of rofecoxib (10 mg/kg, PO, day 21 post surgery) or gabapentin (100mg/kg, PO, day 21 post surgery) significantly attenuated the change in HPWD, however, only gabapentin significantly decreased tactile allodynia.


CONCLUSIONS
The rat medial meniscal tear (MMT) model mimics both nociceptive and neuropathic OA pain and is responsive to both a selective cylooxygenase-2 (COX-2) inhibitor commonly utilized for OA pain (rofecoxib) and a widely prescribed drug for neuropathic pain (gabapentin). The rat MMT model may therefore represent a predictive tool for the development of pharmacologic interventions for the treatment of the symptoms associated with OA.
Bove
S E
SE
Department of Inflammation Biology, Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. susan.bove@pfizer.com
Laemont
K D
KD
Brooker
R M
RM
Osborn
M N
MN
Sanchez
B M
BM
Guzman
R E
RE
Hook
K E
KE
Juneau
P L
PL
Connor
J R
JR
Kilgore
K S
KS
D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D018771:Arthralgia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D000077206:Gabapentin; D006614:Hindlimb; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D007783:Lactones / Q000627:therapeutic use; D008297:Male; D020370:Osteoarthritis, Knee / Q000150:complications / Q000473:pathology*; D051381:Rats; D013450:Sulfones / Q000627:therapeutic use; D016474:Weight-Bearing / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin