Usefulness of antidepressants for improving the neuropathic pain-like state and pain-induced anxiety through actions at different brain sites.
Clinically, it is well known that chronic pain induces depression, anxiety, and a reduced quality of life. There have been many reports on the relationship between pain and emotion. We previously reported that chronic pain induced anxiety with changes in opioidergic function in the central nervous system. In this study, we evaluated the anxiolytic-like effects of several types of antidepressants under a chronic neuropathic pain-like state and searched for the brain site of action where antidepressants show anxiolytic or antinociceptive effects. Sciatic nerve-ligated mice exhibited thermal hyperalgesia and tactile allodynia from days 7 to 28 after nerve ligation. At 4 weeks after ligation, these mice showed a significant anxiety-related behavior in the light-dark test and the elevated plus-maze test. Under these conditions, repeated administration of antidepressants, including the tricyclic antidepressant (TCA) imipramine, the serotonin noradrenaline reuptake inhibitor (SNRI) milnacipran, and the selective serotonin reuptake inhibitor (SSRI) paroxetine, significantly prevented the anxiety-related behaviors induced by chronic neuropathic pain. These antidepressants also produced a significant reduction in thermal hyperalgesia and tactile allodynia. Moreover, the microinjection of paroxetine into the basolateral amygdala or cingulate cortex reduced anxiety-related behavior, and microinjection into the primary somatosensory cortex significantly attenuated thermal hyperalgesia. These findings suggest that serotonergic antidepressants are effective for treating anxiety associated with chronic neuropathic pain and may be useful for treating neuropathic pain with emotional dysfunction such as anxiety. Furthermore, SSRIs show anxiolytic and antinociceptive effects by acting on different brain regions.
Matsuzawa-Yanagida
Kiyomi
K
Department of Anesthesiology, Faculty of Medicine, University of Toyama, Toyama, Japan.
Narita
Minoru
M
Nakajima
Mayumi
M
Kuzumaki
Naoko
N
Niikura
Keiichi
K
Nozaki
Hiroyuki
H
Takagi
Tomoe
T
Tamai
Eiko
E
Hareyama
Nana
N
Terada
Mioko
M
Yamazaki
Mitsuaki
M
Suzuki
Tsutomu
T
D000700:Analgesics; D000818:Animals; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology*; D001921:Brain / Q000187:drug effects*; D003624:Darkness; D006358:Hot Temperature; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000150:complications / Q000473:pathology / Q000523:psychology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology
D000700:Analgesics; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D017367:Selective Serotonin Reuptake Inhibitors