The brain activity changes of tactile allodynia and the analgesic effect of gabapentin in the neuropathic rats
Date Issued
2015
Date
2015
Author(s)
Lin, Hsiao-Chun
Abstract
Neuropathic pain is caused by injury or disease of the somatosensory system. Treating neuropathic pain is difficult because its pathophysiological mechanisms are understood limitedly. Tactile allodynia, the innocuous touch-evoked pain, is one of the major symptoms of neuropathic pain patients. So far the studies of tactile allodynia are focused on the functional alterations in the primary afferents and the spinal dorsal horn neurons, however, the role of brain in the tactile allodynia is still unclear. Gabapentin (GBP) is a first-line analgesic to treat neuropathic pain, but its action sites in the brain remains to be disclosed. In this thesis, we used positron emission tomography (PET) and immunohistochemical methods to investigate the functional alterations in the brain of neuropathic rats under allodynic state, and the action sites of GBP in the brain. We used the spared nerve injury (SNI) model of neuropathic pain. In the SNI model, the tibia and common peroneal nerves of the sciatic nerve were ligated and cut, and leaving the sural nerve intact. The nerve-injured rats developed spontaneous pain, tactile allodynia and thermal hyperalgesia. Then we compared the glucose metabolic rate and neuronal activation markers in the brain of neuropathic rats under allodynic state, and the effect of GBP. The PET results showed glucose metabolic rates increased in the anterior insular cortex (IC), thalamus and cerebellum after nerve-injury, and GBP treatment reversed the increases in the thalamus and cerebellum, and decreased the glucose metabolism in the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). The immunostaining results showed an abundant expression of pERK and c-Fos in the mPFC, ACC and anterior IC. For pERK study, the pERK-positive cells in the neuropathic rats increased significantly in the mPFC and IC than control rats. For c-Fos study, the c-Fos-positive cells in the neuropathic rats increased significantly in the mPFC than control rats. After GBP treatment, the increased expression of pERK and c-Fos decreased significantly. We also demonstrated the pERK- or c-Fos-positive cells were neurons, not the astrocytes. According to our studies, the tactile allodynia affect the neuronal activities in the limbic cortices of neuropathic rats, and the effect of GBP was to suppress the activation of limbic cortices.
Subjects
allodynia
gabapentin
medial prefrontal cortex
anterior cingulate cortex
insular cortex
Type
thesis
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