Effects of intrathecal administration of newer antidepressants on mechanical allodynia in rat models of neuropathic pain.
Antidepressants, especially tricyclic antidepressants (TCAs) are widely used for the treatment of various types of chronic and neuropathic pain. The antinociceptive effects of TCAs are, however, complicated. Therefore, two kinds of newer antidepressants whose functions have been more fully clarified were selected, milnacipran, a serotonin and noradrenaline reuptake inhibitor (SNRI) and paroxetine and fluvoxamine, which are selective serotonin reuptake inhibitors (SSRIs). The antiallodynic effects of intrathecal administration of these newer antidepressants were examined in two rat models of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve and streptozotocin (STZ)-induced diabetic neuropathy. The antiallodynic effect of these antidepressants was evaluated using the von Frey test. The intrathecal administration of milnacipran had an antiallodynic effect in both CCI and STZ-induced diabetic rats in a dose-dependent manner. On the other hand, the intrathecal administration of either paroxetine or fluvoxamine elicited little antiallodynic effect in CCI rats, while both SSRIs had antiallodynic effects in the STZ-induced diabetic rats in a dose-dependent manner. These results indicate a considerable difference to exist in the development and/or maintenance between these two animal models of neuropathic pain and suggest that each of these three antidepressants may be effective for the treatment of diabetic neuropathic pain.
Ikeda
Tetsuya
T
Division of Neurobiology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
Ishida
Yasushi
Y
Naono
Rumi
R
Takeda
Ryuichiro
R
Abe
Hiroshi
H
Nakamura
Tadashi
T
Nishimori
Toshikazu
T
D000700:Analgesics / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003521:Cyclopropanes / Q000008:administration & dosage / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D016666:Fluvoxamine / Q000008:administration & dosage / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D000078764:Milnacipran; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D017374:Paroxetine / Q000008:administration & dosage / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology
D000700:Analgesics; D000928:Antidepressive Agents; D003521:Cyclopropanes; D016666:Fluvoxamine; D000078764:Milnacipran; D017374:Paroxetine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors