title: Inflammation-susceptible Lewis rats show less sensitivity than resistant Fischer rats in the formalin inflammatory pain test and with repeated thermal testing.
abstract: Comparisons between Lewis and Fischer inbred strains of rats are used frequently to study the effect of inherent differences in function of the hypothalamic-pituitary-adrenal axis on pain-relevant traits, including differential susceptibility to chronic inflammatory disease and differential responsiveness to analgesic drugs. Increasing use of genetic models including transgenic knockout mice and inbred strains of rodents has raised our awareness of, and the importance of, thorough characterization (or phenotyping) of the strains of rodents being compared. Furthermore, genetic variability in analgesic sensitivity is correlated with, and may be caused by, genetically determined baseline sensitivity. Thus in this study, baseline inflammatory and thermal nociceptive sensitivities were measured in awake male and female Lewis and Fischer rats to examine whether the results could explain relevant strain differences reported in the literature. The effect of maternal separation was also examined and no effect was found on nociceptive sensitivity, corticosterone responses, or the development of adjuvant-induced arthritis, a model of rheumatoid arthritis. Lewis rats and female rats were more sensitive to thermal nociception in the tail withdrawal test (mean of 3 trials) than Fischer rats and male rats, respectively. Unexpectedly, the more inflammation-susceptible Lewis rats were less sensitive in the formalin inflammatory nociception test, and showed a significant decrease in sensitivity with repeated thermal nociceptive testing, whereas Fischer rats did not. These results affect the interpretation of previously observed results. Further study of the underlying mechanisms and the relevance to differential susceptibility to chronic inflammation is warranted.
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, Suite A 1305 Scaife Hall, 3550 Terrace St., Pittsburgh, PA 15261, USA. william.lariviere@elf.mcgill.ca
authors.forename: William R
authors.initials: WR
authors.lastname: Lariviere
authors.forename: M Abdus
authors.initials: MA
authors.lastname: Sattar
authors.forename: Ronald
authors.initials: R
authors.lastname: Melzack
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001522:Behavior, Animal; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005557:Formaldehyde / Q000009:adverse effects*; D005620:Freund's Adjuvant / Q000031:analogs & derivatives; D006358:Hot Temperature / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011930:Reaction Time / Q000502:physiology; D012737:Sex Factors; D013997:Time Factors
chemical_list: D005557:Formaldehyde; D005620:Freund's Adjuvant; D003345:Corticosterone