The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are involved in physiologic sleep regulation. Administration of exogenous IL-1 beta or TNF-alpha induces increased non-rapid eye movement sleep (NREMS). Inhibition of IL-1 or TNF reduces spontaneous sleep. There is a diurnal rhythm of TNF-alpha mRNA and IL-1 beta mRNA in brain with highest levels occurring during peak sleep periods. Mice lacking either the TNF 55-kD receptor or the IL-1 type I receptor sleep less than do strain controls. IL-1 beta and TNF-alpha are part of a larger biochemical cascade involved in sleep regulation; other somnogenic substances in this cascade include growth hormone-releasing hormone and nitric oxide. Several additional substances are involved in inhibitory feedback mechanisms, some of which inhibit IL-1 and TNF. A major challenge to sleep research is to define how and where these molecular steps produce sleep.

No abstract

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-kappaB activation would attenuate sleep. A NF-kappaB cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 microg for rats, 100 microg for rabbits). On a separate day, time-matched control injections of a cell-permeable inactive control peptide were done in the same animals. The 50-microg dose of IP in rats and the 100-microg dose in rabbits significantly inhibited non-rapid eye movement sleep and rapid eye movement sleep if administered during the light period. Moreover, pretreatment of rabbits with 100 microg of the IP 12 h before intracerebroventricular injection of IL-1beta (10 ng) significantly attenuated IL-1beta-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-kappaB is a crucial factor in physiological sleep regulation.

Our data suggest that insertion of intradermal needles into painful points is a remarkably effective treatment for intractable abdominal scar pain. Analgesia presumably results from inactivation of painful points, through a yet to be elucidated mechanism.

Several well-defined sleep regulatory substances, e.g., interleukin-1β, activate the heterodimeric transcription factor nuclear factor-κB (NF-κB). Several substances that inhibit sleep, e.g., interleukin-4, inhibit NF-κB activation. NF-κB activation promotes production of several additional substances thought to be involved in sleep regulation, e.g., nitric oxide. We investigated, therefore, whether there are diurnal rhythms of NF-κB activation in brain and changes in the activation after sleep deprivation. Mice were kept on a 12:12-h light-dark cycle. In one experiment, groups of mice were killed every 3 h across the 24-h cycle. In another experiment, mice were killed at 1500 after 6 h of sleep deprivation, and a group of control mice were killed at the same time. Nuclear proteins were extracted from each brain tissue sample, and NF-κB-like activity was determined with an electrophoretic mobility shift assay. In cerebral cortex, but not other areas of brain, there was a diurnal rhythm in NF-κB-like activation; highest levels were found during the light period. NF-κB-like activation was higher in cerebral cortex after sleep deprivation compared with values obtained from control mice. The results are consistent with the hypothesis that sleep regulation involves multiple gene events, some of which include enhanced production of sleep regulatory substances, the actions of which involve NF-κB activation.

Proinflammatory cytokines, including interleukin-1beta(IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are involved in sleep regulation. IL-10 is an anti-inflammatory cytokine that inhibits proinflammatory cytokine production. We hypothesized that IL-10 could attenuate sleep. Thirty-one male rabbits were used. Three doses of IL-10 (5 ng, 50 ng, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-10 (250 ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were given to the same rabbits on different days. The two highest doses of IL-10 significantly inhibited spontaneous nonrapid eye movement sleep if IL-10 was given during the light cycle. The highest dose of IL-10 (250 ng) also significantly decreased rapid eye movement sleep. IL-10 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-10 provide additional evidence for the hypothesis that a brain cytokine network is involved in regulation of physiologic sleep.

Various growth factors are involved in sleep regulation. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family; it and its receptors are found in normal brain. Furthermore, cerebral cortical levels of BDNF mRNA have a diurnal variation and increase after sleep deprivation. Therefore, we investigated whether BDNF would promote sleep. Twenty-four male Sprague-Dawley rats (320–380 g) and 25 male New Zealand White rabbits (4.5–5.5 kg) were surgically implanted with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and, on a separate day, one of the following doses of BDNF: 25 or 250 ng in rabbits; 10, 50, or 250 ng in rats. The EEG, brain temperature, and motor activity were recorded for 23 h after the intracerebroventricular injections. BDNF increased time spent in non-rapid eye movement sleep (NREMS) in rats and rabbits and REMS in rabbits. Current results provide further evidence that various growth factors are involved in sleep regulation.