Oxcarbazepine antinociception in animals with inflammatory pain or painful diabetic neuropathy.
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.
Kiguchi
Sumiyoshi
S
Pharmacology Research, R&D, Kissei Pharmaceutical Co. Ltd., 4365-1 Kashiwabara, Hotaka, Minamiazumi, Nagano 399-8304, Japan. sumiyoshi_kiguchi@pharm.kissei.co.jp
Imamura
Takahiro
T
Ichikawa
Kiyoshi
K
Kojima
Masami
M
D000700:Analgesics; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002351:Carrageenan; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000150:complications* / Q000503:physiopathology; D005557:Formaldehyde; D006358:Hot Temperature; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D000078330:Oxcarbazepine; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
D000700:Analgesics; D000701:Analgesics, Opioid; D000889:Anti-Arrhythmia Agents; D005557:Formaldehyde; D008801:Mexiletine; D002220:Carbamazepine; D009020:Morphine; D002351:Carrageenan; D000078330:Oxcarbazepine