TY - JOUR
T1 - Inhibiting astrocytic activation
T2 - A novel analgesic mechanism of ketamine at the spinal level?
AU - Mei, Xiaopeng
AU - Wang, Wei
AU - Wang, Wen
AU - Li, Yunming
AU - Zhang, Hui
AU - Wu, Shengxi
AU - Li, Yunqing
AU - Xu, Lixian
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Astrocytes
KW - N-methyl-d-aspartate
KW - Neuropathic pain
KW - Spinal cord
KW - Spinal nerve ligation
UR - http://www.scopus.com/inward/record.url?scp=65949086600&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65949086600&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2009.06087.x
DO - 10.1111/j.1471-4159.2009.06087.x
M3 - Article
C2 - 19383087
AN - SCOPUS:65949086600
SN - 0022-3042
VL - 109
SP - 1691
EP - 1700
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 6
ER -