Neuroscience letters
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Neuroscience letters · Jan 2006
Comparative StudyEffect of betamethasone on neuropathic pain and cerebral expression of NF-kappaB and cytokines.
Glucocorticoids have been used to treat neuropathic pain for many years, but the underlying mechanisms are still unknown. Recent studies indicate that pathological pain states may be mediated by cytokines. We, therefore, examined the effect of betamethasone on neuropathic pain and the relationship between pain behavior and the expression of cytokines in the brain. ⋯ We found that spinal nerve injury caused long-lasting mechanical and thermal hyperalgesia in the hind paw and stimulated the expression of NF-kappaB, TNFalpha, IL-1beta and IL-10 in the brain. A single epidural injection of betamethasone at the time of nerve injury partially inhibited the development of neuropathic hyperalgesia and reduced the subsequent elevated levels of pro-inflammatory cytokines in the brain, while stimulating the expression of the anti-inflammatory cytokine IL-10. These data support our hypothesis that pro-inflammatory cytokines in the brain may mediate the hyperalgesic effects of spinal nerve injury and that the long-acting anti-hyperalgesic effects of epidural glucocorticoid treatment are due to an inhibitory effect on pro-inflammatory cytokine levels and a stimulatory effect on anti-inflammatory cytokine levels in the brain.
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Neuroscience letters · Jan 2006
Comparative StudyEvidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain.
Descending modulation of spinal processing plays an important role in chronic pain states. Monoamine pathways comprise a major component of descending controls from the brainstem to the spinal cord. Recent emphasis has been on facilitatory actions mediated by the 5-HT3 receptor. ⋯ Spinally administered ondansetron (10, 50, and 100 microg) had no effect on electrical-evoked neuronal responses, but significantly reduced mechanical- and thermal-evoked responses in both the groups of animals. Furthermore, the effects of ondansetron were significantly greater in cancer animals compared to shams. These results therefore suggest a role for descending serotonergic facilitation in CIBP.
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Neuroscience letters · Jan 2006
Comparative StudyEarly increase in mRNA levels of pro-inflammatory cytokines and their interactions in the mouse hippocampus after transient global ischemia.
There is convincing evidence that cytokines are involved in the inflammatory response following cerebral ischemia, but the interactions among the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in the early stage of ischemic reperfusion are not yet completely understood. In this study, we examined the early mRNA expressions of pro-inflammatory cytokines in the ischemic hippocampus after 30 min of bilateral common carotid artery occlusion in C57BL/6J wild-type (WT) and TNF-alpha, IL-1alpha/beta or IL-6 gene knockout (KO) mice utilizing real-time polymerase chain reaction. The mRNA expressions of the pro-inflammatory cytokines TNF-alpha, IL-6 and IL-1beta were significantly induced in ischemic WT mice compared with in the sham-operated mice. ⋯ The IL-1beta mRNA level was very low in ischemic TNF-alpha KO mice and IL-6 KO mice in spite of a small peak observed in both at 24 h. The IL-6 mRNA level was significantly upregulated at all time points in both ischemic WT and TNF-alpha KO mice; however, the peak was delayed by 12-h in IL-1alpha/beta KO mice. In conclusion, the present study indicates that the rapid increases in cytokine levels are interdependent, interactive, and possibly modulate each other in the mouse hippocampus after transient global ischemia.
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Neuroscience letters · Jan 2006
Comparative StudyImpaired hippocampal long-term potentiation in melatonin MT2 receptor-deficient mice.
The pineal product melatonin that acts on specific melatonin receptors has been implicated in pathobiological mechanisms of neuropsychiatric disorders including Alzheimer's disease. We used mice lacking melatonin MT(2) receptors (MT(2) knockouts) to investigate the role of these receptors in synaptic plasticity and learning-dependent behavior. ⋯ Tested in an elevated plus-maze on two consecutive days, wild-type mice showed shorter transfer latencies to enter a closed arm on the second day; this experience-dependent behavior did not occur in MT(2) knockouts. These results suggest that MT(2) receptors participate in hippocampal synaptic plasticity and in memory processes.
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Neuroscience letters · Jan 2006
Comparative StudyAnalgesic effects of capsazepine and resiniferatoxin on bone cancer pain in mice.
In the present paper, we describe the analgesic effects induced by the transient receptor potential vanilloid type 1 (TRPV1) antagonist, capsazepine, and the TRPV1 agonist, resiniferatoxin, on the thermal hyperalgesia induced by the presence of a tibial osteosarcoma or an inflammatory process in mice. The administration of capsazepine abolished the osteosarcoma-induced hyperalgesia at a dose range (3-10 mg/kg; s.c.) ineffective to inhibit the hyperalgesia elicited by the intraplantar administration of complete Freund's adjuvant (CFA). ⋯ Remarkably, a single dose of resiniferatoxin abolished the osteosarcoma-induced hyperalgesia for several days and completely prevented the instauration of thermal hyperalgesia when administered at the initial stages of osteosarcoma development. The potential of drugs acting through TRPV1 for the management of some types of bone cancer pain is proposed.