Many diabetic patients experience chronic neuropathic pain leading to a reduced quality of life which poses a huge economic burden to the health system and society. There is a dire need to develop more efficacious analgesics as the majority of patients respond poorly to available treatments. The predictive validity of animal models for analgesia may be improved by looking to reinstate specific innate rodent well-being behaviours suppressed by pain (e.g. burrowing, hoarding, nesting). Streptozocin (STZ) given systemically to rats induces rapid and sustained changes that are seen in diabetic patients i.e. hyperglycaemia, polydypsia and frequently neuropathic pain. In this study we investigated whether the development of STZ induced diabetes reduces burrowing, hoarding and nesting behaviours of rats and whether these behaviours are improved by housing with a control (CTRL) or STZ partner. This work was conducted in accordance with guidelines established by the Animals (Scientific Procedures) Act 1986 / ASPA Amendment Regulations 2012. Male Wistar rats (325-425g) were administered a single i.p. injection of 65mgkg STZ or 20mM citrate buffer (pH4.5, CTRL). In one batch of animals; CTRL (N=8) or STZ (N=32) evoked static allodynia was measured. In a second batch of animals; CTRL (N=12) or STZ (N=16) were pair housed into 4 CTRL/CTRL , 4 mixed STZ/CTRL or 5 STZ/STZ. Out of the 48 STZ animals, 2 failed to develop diabetes (day 7 blood glucose <16mmol/L) and 2 approached a moderate severity weight loss (20%) and were euthanized. Evoked static allodynia was evaluated using Dixon’s up-down method (1) and burrowing behaviour in the home cage measured the amount of pea shingle (2.5kg) displaced from hollow plastic tubes (320 mm long x 100 mm diameter), as previously described (2). STZ diabetic pairs showed significant polydipsia and polyphagia as early as 2 and 6 days post injection and by day 13 were consuming 30% more food and drinking 6 times more water than CTRL pairs. STZ pairs showed a progressive decrease in 2 hour burrowing compared to CTRL pairs (CTRL: 2296.8±69.5g; STZ: 1268.6±289.4g, ***p<0.001 by day 9) but not mixed pairs (STZ/CTRL: 1611.3 ± 382.9g). By day 9, 64% of STZ diabetic rats had developed static allodynia that was significantly reversed by Pregabalin (30mgkg p.o. over days 14 to 18, ***p<0.001 versus vehicle group). Furthermore it was clear that social grouping of an STZ rat with a CTRL or STZ partner can have a positive impact on individual burrowing. If a STZ diabetic rat was paired with a CTRL rat it burrowed significantly more than a STZ diabetic rat that was paired with another STZ diabetic rat (*p<0.05). Similarly, if a CTRL rat was paired with another CTRL rat it burrowed significantly more than a CTRL rat that was paired with an STZ diabetic rat (*p<0.05). This housing alteration of burrowing behaviour suggests burrowing is measuring affective chronic well-being of both CTRL and STZ diabetic rats. Nesting and hoarding produced no significant trends in this study. Unlike mice, rats do not build nests and therefore this was not a useful measure even for our diabetic rats that needed to thermoregulate. Measurement of hoarding of dry food in the home cage was confounded in the STZ pairs due to their increased polydipsia. Encouragingly, impairment in the naturalistic burrowing response seen in our STZ diabetic rats correlates with the time course development of neuropathic pain and offers a simple, objective way of assessing the impact of pain on well-being in diabetic rats as well as analgesia. Furthermore it is clear that social grouping of an STZ rat with a CTRL partner can have a positive impact on its welfare. (1) Dixon WJ. (1980) Ann Rev Pharmacol Toxicol. 20, 441-62. (2) Deacon RMJ (2006) Nat Protoc;1:1117–9.
|Title of host publication||pA2 online|
|Place of Publication||pA2 online|
|Publication status||Published - Dec 2014|