Oxcarbazepine antinociception in animals with inflammatory pain or painful diabetic neuropathy

Abstract

1. Diabetic neuropathy is one of the most frequent complications of diabetes mellitus. However, the mechanisms underlying these disorders are not yet well defined and it has been reported that currently available analgesics have hardly any ameliorating effect on painful diabetic neuropathy. 2. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine (OCBZ), a keto derivative of carbamazepine (CBZ), in animal models generally used in pain research and in rats and mice with streptozotocin (STZ)-induced diabetes. In addition, we compared the effect of OCBZ with those of CBZ, mexiletine and morphine. 3. Diabetes was induced by injection of STZ at a dose of 300 mg/kg (i.p.) in mice and 50 mg/kg (i.v.) in rats. Experiments were conducted 2 weeks after STZ injection and those animals with a serum glucose level above 400 mg/dL were used for data analysis. Antinociceptive effects of the drugs were evaluated by the paw withdrawal test (normal, STZ-induced diabetic and carrageenin-injected rats), tail-flick test (normal and STZ-induced diabetic mice) and nociceptive behaviour (formalin-injected mice). 4. In the present study, diabetic mice showed thermal hyperalgesia and diabetic rats exhibited mechanical hyperalgesia. From these results, the STZ-induced diabetic animals used in the present study were found to be suitable for research on painful diabetic neuropathy. In STZ-induced diabetic animals, the antinociceptive effects of OCBZ, CBZ and mexiletine were facilitated, whereas the effect of morphine was attenuated, compared with effects in normal animals. 5. Oxcarbazepine inhibited the formalin-induced biphasic pain responses and increased the nociceptive threshold in the case of carrageenin-induced hyperalgesia. In view of these results, inhibition of substance P-mediated pain transmission may be involved in the antinociceptive action of OCBZ. 6. These results indicate that OCBZ has an analgesic action and is a possible therapeutic agent for the treatment of neuropathic pain, such as occurs in painful diabetic neuropathy.

Regression of diabetic complications by islet transplantation in the rat

“…Our data confirm previous reports that streptozotocin-induced diabetes in rats is associated with mechanical hyperalgesia [14]. This result is clinically relevant because it correlates with reports by diabetic patients [9]. In contrast, conflicting data have been reported about thermal perception in experimental DPN, with † † † Fig.…”

“…Patients often have excessive sensitivity to nociceptive stimuli (hyperalgesia) or may perceive normal stimuli as painful (allodynia) [9].…”

Review article: The role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective

“…39 Of relevance to this review, the antinociceptive effects of several anticonvulsants have been evaluated in the rodent formalin pain model (Table I). While both phases 1 and 2 formalin-induced nociception were shown to be reduced by ethosuximide 40,41 and vigabatrin, 42 only phase 2 was reduced by carbamazepine, 43 gabapentin, 44 lamotrigine, 45 oxcarbazepine 46 and pregabalin. 44 Equivocal results were reported for tiagabine 41,45 and valproic acid, 41,47 possibly due to species differences.…”

Pharmacology of 2-[4-(4-Chloro-2-fluorophenoxy)phenyl]-pyrimidine-4-carboxamide: A Potent, Broad-Spectrum State-Dependent Sodium Channel Blocker for Treating Pain States

“…Therefore, it is not surprising that drugs with Na ϩ channel-blocking activity, such as carbamazepine (CBZ), lamotrigine (LTG), mexiletine, and lidocaine, show efficacy in animal pain models (Hunter et al, 1997;De Vry et al, 2004;Kiguchi et al, 2004) and, moreover, have utility in treating pain states in humans (e.g., Mao and Chen, 2000;Jensen, 2002;Petersen et al, 2003). However, these drugs were developed as anticonvulsants, antiarrhythmics, and anesthetics, with no attempt to optimize the Na ϩ channel-blocking activity for treating chronic pain.…”