Behavioural assessment of the effects of tumour growth in rats and the influence of the analgesics carprofen and meloxicam.
Very little is known concerning the occurrence of pain in cancer research models. We wished to establish whether a behaviour-based approach, originally developed to assess postoperative pain, could be used to determine positive effects of the analgesics carprofen and meloxicam in rats that might be experiencing pain during tumour development in an orthotopic model of bladder cancer. An invasive but non-metastatic rat bladder cancer cell line was surgically implanted into the bladder wall of 57 inbred Fisher344 rats. The rats underwent daily clinical assessments. When clinical signs consistent with chronic pain were apparent, behavioural data were collected from 44 animals during 2 x 10 min periods, immediately before and one hour after a subcutaneous injection of either physiological saline (0.9%; 0.2 ml/100 g), carprofen (5 mg/kg) or meloxicam (2 mg/kg). Treatment-associated behaviour changes were then compared between groups. The lack of active behaviour, both before and after each treatment, was consistent with established clinical signs of pain. The rats were so inactive following the treatment that the behavioural technique we had previously developed was of comparatively little use in determining either pain severity or analgesic efficacy. One very prominent effect, however, was an increase in ventral abdominal licking in the control (saline) group. As this was absent in rats given meloxicam or carprofen, and has previously been considered to indicate pain emanating from damaged tissue, it was concluded that the analgesic-treated rats gained at least some benefit from the drug treatments, but it was not possible to gauge the extent of this. Handling for examination or treatment may have intensified pain in rats in the control group, and so this should be avoided whenever possible. It is likely that post-surgical pain differs markedly from cancer pain, so a different set of behavioural markers may be needed to assess it effectively. More intensive behaviour monitoring may help to develop a suitable technique for detecting the onset of, and assess the severity of pain that may occur during tumour development.
Roughan
John V
JV
Comparative Biology Centre, The Medical School, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK. j.v.roughan@newcastle.ac.uk
Flecknell
Paul A
PA
Davies
Barry R
BR
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002227:Carbazoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D000077239:Meloxicam; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy; D051381:Rats; D011916:Rats, Inbred F344; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000150:complications*
D002227:Carbazoles; D013843:Thiazines; D013844:Thiazoles; C007005:carprofen; D000077239:Meloxicam