Alleviating neuropathic pain mechanical allodynia by increasing Cdh1 in the anterior cingulate cortex

نویسندگان

  • Wei Tan
  • Wen-Long Yao
  • Rong Hu
  • You-You Lv
  • Li Wan
  • Chuan-Han Zhang
  • Chang Zhu
چکیده

BACKGROUND Plastic changes in the anterior cingulate cortex (ACC) are critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. Cdh1, a co-activator subunit of anaphase-promoting complex/cyclosome (APC/C) regulates synaptic differentiation and transmission. Based on this, we hypothesised that the APC/C-Cdh1 played an important role in long-term plastic changes induced by neuropathic pain in ACC. RESULTS We employed spared nerve injury (SNI) model in rat and found Cdh1 protein level in the ACC was down-regulated 3, 7 and 14 days after SNI surgery. We detected increase in c-Fos expression, numerical increase of organelles, swollen myelinated fibre and axon collapse of neuronal cells in the ACC of SNI rat. Additionally, AMPA receptor GluR1 subunit protein level was up-regulated on the membrane through a pathway that involves EphA4 mediated by APC/C-Cdh1, 3 and 7 days after SNI surgery. To confirm the effect of Cdh1 in neuropathic pain, Cdh1-expressing lentivirus was injected into the ACC of SNI rat. Intra-ACC treatment with Cdh1-expressing lentivirus vectors elevated Cdh1 levels, erased synaptic strengthening, as well as alleviating established mechanical allodynia in SNI rats. We also found Cdh1-expressing lentivirus normalised SNI-induced redistribution of AMPA receptor GluR1 subunit in ACC by regulating AMPA receptor trafficking. CONCLUSIONS These results provide evidence that Cdh1 in ACC synapses may offer a novel therapeutic strategy for treating chronic neuropathic pain.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The Analgesic and Anxiolytic Activity of Resveratrol Mediated by Different Sub-Types of α-Adrenoceptors of Anterior Cingulate Cortex Following Neuropathic Pain in Male Rats

Background and Objective: The mechanism of analgesic and anxiolytic activity of resveratrol in neuropathic pain conditions remains obscure. The present study was conducted to examine whether the analgesic and anxiolytic activities of resveratrol are associated with α1- and α2-adrenoceptors of the anterior cingulate cortex (ACC), which is a key area of the cortex in the pain process, following n...

متن کامل

Electrical stimulation of the anterior cingulate cortex in a rat neuropathic pain model.

BACKGROUND Electrical stimulation is currently employed to treat several neurological conditions, including pain and Parkinson's disease. It is one of several minimally invasive alternatives to drug treatments for painful conditions. A number of studies have shown that the anterior cingulate cortex (ACC) plays an important role in the processing of pain and pain modulation. The purpose of this ...

متن کامل

Alleviation of neuropathic pain by regulating T-type calcium channels in rat anterior cingulate cortex

BACKGROUND It has been demonstrated that administration of T-type calcium channel (TCC) inhibitors could relieve the neuropathic pain by intraperitoneally or intrathecally. TCCs are not only expressed in dorsal root ganglia or dorsal horn, but also in some of the pain associated brain regions. In the present study, we sought to investigate whether modulating TCCs in the anterior cingulate corte...

متن کامل

Electrolytic lesion of the anterior cingulate cortex decreases inflammatory, but not neuropathic nociceptive behavior in rats.

The present study investigated the effect of lesions of the anterior cingulate cortex (ACC) on mechanical allodynia/hyperalgesia after L5 ligation or on inflammatory nociceptive responses following formalin injection in the rat. For both the neuropathic and inflammatory pain models, three groups of animals were used. The control groups consisted of a group of sham lesioned animals and a group o...

متن کامل

Long non-coding RNA CCAT1 modulates neuropathic pain progression through sponging miR-155

Neuropathic pain is caused by dysfunction or primary injury of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) play important roles in the development of neuropathic pain. However, the effects of lncRNA colon cancer associated transcript-1 (CCAT1) in neuropathic pain have not been reported. The model of bilateral sciatic nerve chronic constriction injuries (bCCI) is regarded as ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2015