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Recent advances in optical imaging techniques have made it possible to monitor neural activity and provided powerful tools to reveal the spatiotemporal patterns of neural activity. We used optical imaging to determine whether nerve injury affects excitability of the sensory cortex. Male Sprague-Dawley rats were subjected to neuropathic surgery consisting of a tight ligation and transection of the left tibial and sural nerves while under pentobarbital anesthesia. The rats were reanesthetized with urethane two weeks post-operatively, and the exposed cortex surfaces were stained with a voltage-sensitive dye (di-2-ANEPEQ). After electrical stimulation of the receptive field, optical signals from the cerebral cortex were recorded using an optical imaging system. Increased optical intensity and an enlarged area of activation were observed in the cerebral cortex of neuropathic rats during electrical stimulation compared to normal or sham-operated rats. Higher electric stimulation resulted in more intensity and a larger area of activation in neuropathic rats. These results suggest that cortical excitability, resulting from peripheral stimulation, may be affected by nerve injury, which indicates a degree of neural plasticity.

As imaging technology develops, magnetic resonance imaging (MRI) has furthered our understanding of brain function by clarifying the anatomical structure and generating functional imaging data related to information processing in pain conditions. Recent studies have reported that manganese (Mn(2+))-enhanced MRI (MEMRI) provides valuable information about the functions of the central nervous system. The aim of this study was to identify specific brain regions activated during noxious electric stimulation using high-resolution MEMRI. Male Sprague Dawley rats were divided into three groups: naive, sham electrical stimulation, and noxious electric stimulation. Under urethane with α-chloralose mixture anesthesia, a catheter was placed in the external carotid artery to administrate 20% mannitol and manganese chloride (25mM MnCl2). Noxious electric stimulation (2Hz, 10V) was applied to the hind paw with a needle electrode. Stimulation-induced neuronal activation was detected using 4.7-T MRI. In response to noxious electrical stimulation, remarkable Mn(2+)-enhanced signals were observed in the agranular insular cortex, auditory cortex, primary somatosensory cortex of the hind limb, and granular and dysgranular insular cortex, which correspond to sensory tactile electric stimulus to the hindpaws. These results indicate that the combination of MEMRI with activity-induced Mn(2+)-dependent contrast can delineate functional areas in the rat brain.

It has been well documented that there is opioid resistance in neuropathic pain. This indicates that the endogenous opioid system may not be involved effectively in modulating neuropathic pain. The present study sought to determine if activation of the descending pain inhibition system might produce analgesia in the animal neuropathic model we developed. Under ketamine anesthesia, male Sprague-Dawley rats were chronically implanted with stimulating electrodes in the ventral periaqueductal gray matter (PAG) and both the tibial and sural nerves of the sciatic nerve branches were severed. Pain sensitivity was measured with a von Frey filament and acetone applied to the sensitive area for 1 week postoperatively. Rats with neuropathic pain syndrome after transection of the tibial and sural nerves were tested as to the analgesic effects of ventral PAG stimulation for an additional two weeks. Electrical stimulation of the ventral PAG turned out to be highly effective in alleviating neuropathic pain. Mechanical allodynia and cold allodynia were reduced by PAG stimulation. Naloxone reversed the antiallodynic effects of ventral PAG stimulation. These results suggest that activation of the descending pain inhibition system including the ventral PAG reduces neuropathic pain syndrome and that opiates are involved in this system.

FK506 has been originally classified as an immunosuppressant and is known to exhibit neurotrophic actions in vitro and protective effects on some neurological conditions. We investigated the neuroprotective effects of FK506 on kainic acid (KA)-induced neuronal death in organotypic hippocampal slice cultures (OHSCs). After an 18 h KA (5 microM) treatment, significantly neuronal death was detected in the CA3 region using propidium iodide staining. However, neuronal death was significantly prevented at 24 and 48 h after treatment with 0.1 microM FK506. Using cresyl violet staining, we also observed that an increased number of CA3 neurons survived in the 0.1 microM FK506 group compared to the KA only group. Based on the results of the Western blot analysis, the expressions of 5-lipoxygenase and caspase-3 were reduced 24h after 0.1 microM FK506 treatment. The levels of superoxide dismutase (SOD) and phospho-Akt expression were increased by treatment with 0.1 microM FK506. These results suggest that FK506 may have a positive role in protecting neurons against cell death in the KA injury model of OHSCs.

Single unit responses of the primary somatosensory (SI) cortical neurons to the stimulation of the forepaw single digit were monitored in anesthetized rats before and after subcutaneous injection of lidocaine to an ipsilateral homologous receptive field (IHRF). Quantitative determination of the temporal changes of afferent sensory transmission was done by analyzing poststimulus time histograms of unit responses. Temporary deafferentation to the IHRF induced immediate, but reversible suppression of afferent sensory transmission in the SI cortex and this suppression lasts up to 35 min post-deafferentation period (during 10-15 min, -21.81 +/- 5.9%, P < 0.01). This result suggests that temporary absence of afferent inflow from the digit to the SI cortex may exert interhemispheric modulation of afferent sensory transmission in the opposite somatosensory cortex of anesthetized rats.