Inhibiting astrocytic activation: a novel analgesic mechanism of ketamine at the spinal level?
Although ketamine is widely used as an analgesic agent and has an anti-allodynic effect on neuropathic pain, the underlying analgesic mechanisms are not fully explained by the modern 'neuronal-based' theories. As emerging studies have focused on the critical role of spinal astrocytes in the pathological pain states, we have hypothesized that there exist some 'astrocytes-related' mechanisms in the analgesic function of ketamine. In the present study, using the spinal nerve ligation (SNL) pain model, we investigated the anti-nociceptive effects of intraperitoneal or intrathecal ketamine on SNL-induced neuropathic pain response, meanwhile, we investigated the astrocytic activation after ketamine administration on SNL rats. Behavioral data showed that either intraperitoneal or intrathecal ketamine inhibited SNL-induced allodynia, however, immunohistochemistry showed that SNL induced astrocytic activation was suppressed by intrathecal but not intraperitoneal ketamine. Using quantitative Western blot analysis, our report showed that intrathecal ketamine down-regulated glial fibrillary acidic protein expression, suggesting inhibition of SNL-induced astrocytic activation, which wasn't influenced by intraperitoneal administration. We conclude that intraperitoneal ketamine could alleviate SNL-induced neuropathic pain via the classical 'neuronal-based' mechanisms, but in addition, 'astrocytes-related' mechanisms were also important underlying the anti-allodynic effect of intrathecal ketamine.
Mei
Xiaopeng
X
Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an, China.
Wang
Wei
W
Wang
Wen
W
Li
Yunming
Y
Zhang
Hui
H
Wu
Shengxi
S
Li
Yunqing
Y
Xu
Lixian
L
D000700:Analgesics / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008026:Ligation / Q000379:methods; D008297:Male; D010146:Pain / Q000209:etiology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000150:complications*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000700:Analgesics; D005904:Glial Fibrillary Acidic Protein; D007649:Ketamine