Abstract
Aim. To document the influence of diet composition on the incidence and temporal progression of the diabetic neuropathy parameters, tactile allodynia and opioid hyposensitivity, in the ZDF rat model of Type 2 diabetes. Methods. Following baseline measurements of blood glucose levels (BGLs), 24 h water intake and von Frey paw withdrawal thresholds (PWTs) in ZDF rats (n = 24), rats were randomly assigned to one of four groups (n = 6 per gp) with each group administered a different diet from 7-weeks of age as follows: (i) the Purina 5008 diet, (ii) a locally-produced diet of similar composition to Purina 5008, (iii) a diabetogenic diet, and (iv) standard rat chow. The temporal development and maintenance of tactile allodynia was assessed using calibrated von Frey filaments. The anti-allodynic efficacy and potency of single bolus s.c. doses of morphine or oxycodone were assessed at 10, 20, 26 and 28 weeks of age using von Frey filaments. Results. ZDF rats developed hyperglycaemia between 9 and 14 weeks of age. Persistently high BGLs (>20 mM) resulted in the development of tactile allodynia and opioid hyposensitivity in all ZDF rats and there was a temporal development of hyposensitivity to both morphine and oxycodone in all ZDF rats irrespective of the administered diet. Conclusions. Sustained hyperglycaemia for a period of >16 weeks resulted in the development of tactile allodynia, the defining symptom of painful diabetic neuropathy, as well as opioid hyposensitivity in ZDF rats irrespective of the administered diet.
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