Pharmacological characterisation of a rat model of incisional pain.
1. Both clinical and preclinical models of postsurgical pain are being used more frequently in the early evaluation of new chemical entities. In order to assess the validity and reliability of a rat model of postincisional pain, the effects of different classes of clinically effective analgesic drugs were evaluated against multiple behavioural end points. 2. Following surgical incision, under general anaesthesia, of the plantar surface of the rat hind paw, we determined the time course of mechanical hyperalgesia, tactile allodynia and hind limb weight bearing using the Randall-Selitto (paw pressure) assay, electronic von Frey and dual channel weight averager, respectively. Behavioural evaluations began 24 h following surgery, and were continued for 9-14 days. 3. Mechanical hyperalgesia, tactile allodynia and a decrease in weight bearing were present on the affected limb within 1 day of surgery with maximum sensitivity 1-3 days postsurgery. Accordingly, we examined the effect of nonsteroidal antiinflammatory drugs (NSAIDs), morphine and gabapentin, on established hyperalgesia and allodynia, 1 day following plantar incision.4. In accordance with previous reports, both systemic morphine and gabapentin administration reversed mechanical hyperalgesia and tactile allodynia in the incised rat hind paw. Both drugs were more potent against mechanical hyperalgesia than tactile allodynia. 5. All of the NSAIDs tested, including cyclooxygenase 2 selective inhibitors, reversed mechanical hyperalgesia and tactile allodynia in the incised rat hind paw. The rank order of potency for both hyperalgesia and allodynia was indomethacin > celecoxib > etoricoxib > naproxen. 6. We have investigated the potency and efficacy of different classes of analgesic drugs in a rat model of postincisional pain. The rank order of potency for these drugs reflects their utility in treating postoperative pain in the clinic. As these compounds showed reliable efficacy across two different behavioural end points, the Randall-Selitto (paw pressure) assay and electronic von Frey, these methods may prove useful in the study of postsurgical pain and the assessment of novel treatments.
Whiteside
Garth T
GT
Neuropharmacology, Purdue Pharma LP, 6 Cedar Brook Drive, Cranbury, NJ 08512, USA. garth.whiteside@pharma.com
Harrison
James
J
Boulet
Jamie
J
Mark
Lilly
L
Pearson
Michelle
M
Gottshall
Susan
S
Walker
Katharine
K
D000588:Amines / Q000494:pharmacology; D000700:Analgesics / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000068579:Celecoxib; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D000077613:Etoricoxib; D005528:Foot / Q000601:surgery; D000077206:Gabapentin; D006614:Hindlimb; D006930:Hyperalgesia / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000293:injuries; D009288:Naproxen / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010149:Postoperative Pain / Q000188:drug therapy*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D016474:Weight-Bearing / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; D005680:gamma-Aminobutyric Acid; D009288:Naproxen; D000077206:Gabapentin; D009020:Morphine; D000068579:Celecoxib; D000077613:Etoricoxib; D007213:Indomethacin