Pain is a major symptom in cancer patients, and most cancer patients with advanced or terminal cancers suffer from chronic pain related to treatment failure and/or tumor progression. In the present study, we examined the development of cancer pain in mice. Murine hepatocarcinoma cells, HCa-1, were inoculated unilaterally into the thigh or the dorsum of the foot of male C3H/HeJ mice. Four weeks after inoculation, behavioral signs were observed for mechanical allodynia, cold allodynia, and hyperalgesia using a von Frey filament, acetone, and radiant heat, respectively. Bone invasion by the tumor commenced from 7 days after inoculation of tumor cells and was evident from 14 days after inoculation. Cold allodynia but neither mechanical allodynia nor hyperalgesia was observed in mice that received an inoculation into the thigh. On the contrary, mechanical allodynia and cold allodynia, but not hyperalgesia, were developed in mice with an inoculation into the foot. Sometimes, mirror-image pain was developed in these animals. These results suggest that carcinoma cells injected into the foot of mice may develop severe chronic pain related to cancer. This animal model of pain would be useful to elucidate the mechanisms of cancer pain in humans.
Animals ; *Behavior, Animal ; Bone and Bones/pathology ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cold ; Disease Models, Animal ; Foot ; Liver Neoplasms/pathology ; Male ; Mice ; Mice, Inbred C3H ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Neoplasms/*complications ; Pain/*etiology/physiopathology/*psychology ; Pain Threshold ; Physical Stimulation ; Research Support, Non-U.S. Gov't ; Thigh

Ascorbic acid (AA) and dehydroascorbic acid (DHA) are known to have protective effects in experimental central nerve system disorder models such as stroke, ischemia, and epileptic seizures. The present study was conducted to examine the protective effect of AA and DHA on kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures (OHSC). Protective effects of AA and DHA on KA-induced cell death were evaluated by analyzing caspase-3. In addition, to determine if the prooxidant effect of AA is related to iron, the effect of AA on cell death was examined using desferrioxamine (DFO), an iron chelator. After 12h-KA treatment, significant delayed neuronal death was detected in CA3 region, but not in CA1. The AA (500 micrometer) and DHA (100 and 500 micrometer) pretreatments significantly prevented cell death by inhibiting caspase-3 activation in CA3 region. In the concentration of 1,000 micrometer, however, AA pretreatment might have prooxidant effect, but AA-induced oxidative reaction is mainly not related to transition metal ions. These data showed that the pretreatments of intermediate-dose AA and DHA protected KA-induced neuronal damage in OHSCs and co-pretreatment of AA and DFO did not affect cell death except for a few cases. These data suggest that both AA and DHA pretreatment have antioxidant or prooxidant effect depending on doses treated on KA-induced neuronal injury and the possible prooxidant effect of AA may not depend on the Fenton reaction.
Ascorbic Acid ; Caspase 3 ; Cell Death ; Deferoxamine ; Dehydroascorbic Acid ; Epilepsy ; Ions ; Iron ; Ischemia ; Kainic Acid ; Neurons ; Stroke

The spontaneous axon regeneration of damaged neurons is limited after spinal cord injury (SCI). Recently, mesenchymal stem cell (MSC) transplantation was proposed as a potential approach for enhancing nerve regeneration that avoids the ethical issues associated with embryonic stem cell transplantation. As SCI is a complex pathological entity, the treatment of SCI requires a multipronged approach. The purpose of the present study was to investigate the functional recovery and therapeutic potential of human MSCs (hMSCs) and polymer in a spinal cord hemisection injury model. Rats were subjected to hemisection injuries and then divided into three groups. Two groups of rats underwent partial thoracic hemisection injury followed by implantation of either polymer only or polymer with hMSCs. Another hemisection-only group was used as a control. Behavioral, electrophysiological and immunohistochemical studies were performed on all rats. The functional recovery was significantly improved in the polymer with hMSC-transplanted group as compared with control at five weeks after transplantation. The results of electrophysiologic study demonstrated that the latency of somatosensory-evoked potentials (SSEPs) in the polymer with hMSC-transplanted group was significantly shorter than in the hemisection-only control group. In the results of immunohistochemical study, beta-gal-positive cells were observed in the injured and adjacent sites after hMSC transplantation. Surviving hMSCs differentiated into various cell types such as neurons, astrocytes and oligodendrocytes. These data suggest that hMSC transplantation with polymer may play an important role in functional recovery and axonal regeneration after SCI, and may be a potential therapeutic strategy for SCI.
Animals ; Astrocytes ; Axons ; Electrophysiology ; Embryonic Stem Cells ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Nerve Regeneration ; Neurons ; Oligodendroglia ; Polymers ; Rats ; Regeneration ; Spinal Cord ; Spinal Cord Injuries ; Transplants

Methylprednisolone (MP), a glucocorticoid steroid, has an anti-inflammatory action and seems to inhibit the formation of oxygen free radicals produced during lipid peroxidation in a spinal cord injury (SCI). However, the effects of MP on the functional recovery after a SCI is controversial. The present study was conducted to determine the effects of MP on the recovery of neural conduction following a SCI. A SCI was produced using the NYU spinal cord impactor. A behavioral test was conducted to measure neurological disorders, and motor evoked potentials (MEPs) were recorded. According to the behavioral test, using BBB locomotor scaling, MP-treated animals showed improved functional recoveries when compared to salinetreated animals. MEP latencies in the MP-treated group were shortened when compared to those in the control group. Peak amplitudes of MEPs were larger in the MP-treated group than those in the control group. The thresholds of MEPs tended to be lower in the MP-treated group than those in the control group. These results suggest that MP may improve functional recovery after a SCI.
Animals ; Disease Models, Animal ; Electrophysiology ; Evoked Potentials, Motor/*drug effects ; Free Radicals ; Glucocorticoids/metabolism ; Male ; Methylprednisolone/*pharmacology ; Neurons/*drug effects ; Oxygen/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid/metabolism ; Research Support, Non-U.S. Gov't ; Sodium Chloride/pharmacology ; Spinal Cord/pathology ; Spinal Cord Injuries/*drug therapy ; Time Factors