Background:Diabetic neuropathy is a complication of diabetes mellitus that develops in about 50% of people with diabetes. Despite its widespread occurrence and devastating effects, this complication is still not fully understood, and there is no treatment available to prevent its development.Methods:In this study, immunocytochemistry for activating transcription factor 3, a marker for cell injury, was used to investigate the stress response in dorsal root ganglion neurons in both in vitro and ex vivo models of diabetic neuropathy.Results:Our findings showed increased activating transcription factor 3 expression in hyperglycemic culture conditions and in dorsal root ganglion neurons isolated from diabetic rats. Glial cell line-derived neurotrophic factor, a substance with known neuroprotective properties, was able to reduce diabetes mellitus-induced neuronal stress in vitro, while gabapentin and carbamazepine, currently used to treat neuropathic pain, showed only limited effects.Conclusion:Growth factors may have a therapeutic benefit as neurotrophic agents in the treatment of diabetic peripheral neuropathy, but gabapentin and carbamazepine have no direct protective effect on sensory neurons. This research also indicates that immunocytochemistry for activating transcription factor 3 is a valuable tool for evaluation of pharmacological substances in dorsal root ganglion cultures.

Rats that had received 3% alcohol, 0.01% cocaine, or 0.002% fentanyl as the only beverage over 10 days showed marked preference for the drug solution when water was made available as a second fluid in a separate bottle. Treatment with low doses of ritanserin, a specific central serotonin 5-HT2 antagonist, rapidly reversed drug preference without changing total fluid intake. Quantitatively, the reduction in drug consumption was greater for alcohol than for cocaine and greater for cocaine than for fentanyl. This is probably related to differences in the reinforcing potential of the three drugs.

The clinically available opioids have different physicochemical properties, resulting in differences in clinical profile with regard to potency, onset, and duration of activity. However, they all have comparable side-effects after acute systemic application. Several approaches can be used to overcome these side-effects. The following approaches, with special emphasis on the perioperative use of the opioids, are discussed: (1) the use of alternative routes of administration, such as via the spine (epidurally and intrathecally); (2) optimization of opioid delivery by means of slow-release preparations, chronic infusions with indwelling catheters, and transdermal delivery systems; (3) use of additional agents to potentiate the analgesic properties of the opioids so that the dose of opioid can be reduced; and (4) searching for new analgesics on the basis of knowledge of the pain-transmission system and the different opioid receptors with their functional interactions.

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