The impact of bodyweight and body condition on behavioral testing for painful diabetic neuropathy in the streptozotocin rat model.
The streptozotocin (STZ)-induced diabetes model is widely used for the induction of neuropathy in the rat. In this model, diabetic animals often display chronic illness, which raises objections not only on ethical but also on scientific grounds. In this study, the investigators set out to determine the impact of bodyweight and body condition (BC) on behavioral testing in the rat. Animals were allocated to four different groups as a function of their bodyweight, in particular one control group and three experimental groups with different starting weights (low bodyweight [LBW], medium bodyweight [MBW] and high bodyweight [HBW]), the groups having been rendered diabetic with an intraperitoneal injection of STZ (65mg/kg). Bodyweight, blood glucose, body condition and thresholds for mechanical hyperalgesia and tactile allodynia were measured or evaluated over a 68-day period. Animals with a LBW at the start of the experiment showed a gradual increase in BW with a decrease in mechanical nociceptive thresholds, while MBW and HBW animals presented a decrease in both thresholds and BW. The body condition score (BCS) decreased in all STZ-treated groups over time. Since correlations between mechanical thresholds and BW were similar between the control group and the HBW and MBW groups, the loss in BW clearly contributed to the decrease in thresholds. In the LBW group, thresholds and BW correlated negatively, so that the decrease in thresholds was mainly caused by the development of a painful neuropathy. From an ethical and a scientific point of view, in the STZ-induced diabetic neuropathy model, animals should be chosen on the basis of bodyweight and it must also be ensured that STZ is correctly dosed.
Hoybergs
Yves M J J
YM
CNS Discovery Research, Johnson & Johnson Pharmaceutical Research & Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. yhoyberg@prdbe.jnj.com
Biermans
Ria L V
RL
Meert
Theo F
TF
D032761:Animal Experimentation / Q000941:ethics*; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley