There is no effective treatment for intractable postherpetic neuralgia. Because there is evidence that postherpetic neuralgia has an inflammatory component, we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder.

Nuclear factor-κB (NF-κB) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1β (IL-1β), tumor necrosis factor-α, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-κB activation would attenuate sleep. A NF-κB cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 μg for rats, 100 μg 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-μg dose of IP in rats and the 100-μg 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 μg of the IP 12 h before intracerebroventricular injection of IL-1β (10 ng) significantly attenuated IL-1β-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-κB is a crucial factor in physiological sleep regulation.

Central noradrenergic neurones have a role in alertness, analgesia, and thermoregulation; these neurones are also involved in the mechanism of anaesthesia. Locus coeruleus neurones innervate various central nervous regions including the cerebral cortex and hippocampus, and are responsible for wakefulness and analgesia. We hypothesized that these neurones are also involved in both activation of the γ-aminobutyric acid type A (GABA(A)) receptor and inhibition of N-methyl-d-aspartate (NMDA) receptor-mediated anaesthesia. Forty-seven male rats were used to compare duration of anaesthesia before and 10 days after noradrenergic neurone depletion after intraperitoneal (i.p.) administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 0, 5, and 50 mg kg(-1)). The animals received i.p. thiopental (GABA anaesthetic, 45 mg kg(-1)) or ketamine (NMDA anaesthetic, 100 mg kg(-1)). We also tested the effects of coerulean noradrenergic neurone depletion on i.p. ketamine analgesia (15 mg kg(-1)) using the hot-plate test in a further 21 male rats. At the end of each experiment, norepinephrine contents in the cerebral cortex and hippocampus were measured. I.P. DSP-4 5 and 50 mg kg(-1) significantly decreased ketamine anaesthesia duration by 12.7% and 22.4%, increased thiopental anaesthesia duration by 10.8% and 24.5%, and reduced ketamine-increased hot-plate latency by 55.2% and 68.1%, respectively. In addition, i.p. DSP-4 5 and 50 mg kg(-1) significantly reduced norepinephrine contents in coerulean brain regions by ∼20% and ∼75%, respectively. There were significant correlations between norepinephrine contents in coerulean brain regions and anaesthesia durations and ketamine analgesia. The present data indicate that coerulean noradrenergic neurones may be responsible for both GABA- and NMDA-mediated anaesthetic actions.

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.