when interpreting these findings, particularly when drugs are delivered systemically. The extreme metabolic profile of diabetic rodents, with raging polydypsia, polyphagia, polyuria, and attendant changes to the digestive and urinary systems and the blood-brain and blood-nerve barriers can alter many aspects of pharmacokinetics and drug distribution, so that simplistic interpretations of shifts in dose-effect curves of systemically delivered drugs between control and diabetic animals can be misleading and need not reflect changes in receptor number or function (82,83). Direct intrathecal delivery of drugs overcomes some of these issues, but agents delivered in this manner still distribute to the higher CNS (84) and can be subject to altered access and clearance mechanisms. Although pharmacological studies have value for assessing potential efficacy of drugs in altering behavioral indices of nociception and neuropathic pain in animals, their value for investigating aetiological mechanisms is tied to concurrent use of other techniques for assessing spinal receptor number and function.
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