Abstract
Atomoxetine is a selective noradrenaline reuptake inhibitor drug. Based on the knowledge that agents increasing monoamine levels in the central nervous system have therapeutic potential for neuropathic pain, it is planned to investigate the possible efficacy of atomoxetine on diabetes-induced hyperalgesia, in this study. Randall-Selitto (mechanical noxious stimuli) and Hargreaves (thermal noxious stimuli) tests were used to evaluate nociceptive perception of rats. Obtained data indicated that streptozotocin-induced diabetes causes significant decreases in the paw withdrawal threshold and paw withdrawal latency values of the animals, respectively. However, atomoxetine administered at 3 mg/kg/day for 7 and 14 days improved these diabetes-induced hyperalgesia responses. Furthermore, antihyperalgesic activity was antagonized with α-methyl-para-tyrosine methyl ester, phentolamine, propranolol, and sulpiride pre-treatments. The same effect was not reversed, however, by SCH 23390. These findings demonstrated, for the first time, that atomoxetine possesses significant antihyperalgesic activity on diabetes-induced neuropathic pain and this effect seems to be mediated by α- and β-adrenergic and D2/D3 dopaminergic receptors. Results of this present study seem to offer a new indication for an old drug; atomoxetine, but these preclinical data should first be confirmed with further well-designed clinical trials.
Highlights
Chronic exposure to hyperglycemia is known to cause serious damage to the nervous system of patients with diabetes mellitus
Results acquired from the Bonferroni multiple comparison tests demonstrated that in all of the diabetic groups “paw withdrawal threshold” values of rats measured at 4th weeks were significantly lower than those measured before the induction of diabetes (Week 0) (Figure 1.)
No significant interaction was detected between the “atomoxetine treatment” and antihyperalgesic responses in the Randall-Selitto tests =(p 2.06
Summary
Chronic exposure to hyperglycemia is known to cause serious damage to the nervous system of patients with diabetes mellitus. Atomoxetine (Strattera® ) is the first non-stimulant drug approved by FDA for the management of attention deficit hyperactivity disorder (ADHD) It is classified as a “selective noradrenaline reuptake inhibitor” and its mechanism of action has been associated with the enhancement in the levels of intra-synaptic noradrenaline in the central nervous system. Drugs increasing noradrenaline levels in the central nervous system may have a therapeutic potential for patients suffering from the neuropathic pain disorders. In this context, it can be hypothesized that atomoxetine, as a selective noradrenaline reuptake inhibitory drug, may be effective in the treatment of neuropathic pain. In this study, it was planned to investigate promising efficacy of atomoxetine on mechanical and thermal hyperalgesia developing in diabetic rats, and to elucidate the possible pharmacological mechanisms underlying the effect
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