Effects of intrathecal administration of newer antidepressants on mechanical allodynia in rat models of neuropathic pain.

Abstract

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.

• Authors: Tetsuya Ikeda, Yasushi Ishida, Rumi Naono, Ryuichiro Takeda, Hiroshi Abe, Tadashi Nakamura, Toshikazu Nishimori
• Journal: Neuroscience research (Neurosci Res) Vol. 63 Issue 1 Pg. 42-6 (Jan 2009) ISSN: 0168-0102 [Print] Ireland
• PMID: 18992286 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Antidepressive Agents
• Cyclopropanes
• Serotonin Uptake Inhibitors
• Serotonin
• Paroxetine
• Milnacipran
• Fluvoxamine

Topics

• Analgesics (administration & dosage, therapeutic use)
• Animals
• Antidepressive Agents (administration & dosage, therapeutic use)
• Cyclopropanes (administration & dosage, therapeutic use)
• Diabetes Mellitus, Experimental (complications)
• Diabetic Neuropathies (drug therapy, metabolism, physiopathology)
• Disease Models, Animal
• Fluvoxamine (administration & dosage, therapeutic use)
• Hyperalgesia (drug therapy, metabolism, physiopathology)
• Injections, Spinal
• Male
• Milnacipran
• Pain Threshold (drug effects, physiology)
• Paroxetine (administration & dosage, therapeutic use)
• Peripheral Nervous System Diseases (drug therapy, metabolism, physiopathology)
• Rats
• Rats, Sprague-Dawley
• Sciatic Neuropathy (drug therapy, metabolism, physiopathology)
• Serotonin (metabolism)
• Selective Serotonin Reuptake Inhibitors (administration & dosage, therapeutic use)
• Spinal Cord (drug effects, physiopathology)