Aino Alila

Dexamethasone attenuates exercise-induced dental analgesia in man

The effect of dexamethasone on exercise-induced adrenocorticotropin (ACTH) secretion and dental analgesia was studied in healthy human subjects. Different levels of exercise (100-200 W) were produced by a cycle ergometer. Dental pain thresholds were tested with a constant current stimulator. Dental pain thresholds were elevated with increasing work loads, and the elevation was still significant 30 min after the end of the exercise. Dexamethasone produced a significant reversal of exercise-induced pain threshold elevations concomitantly with the suppression of exercise-induced ACTH release. The results suggest that the corticotropin releasing factor-ACTH axis is involved in the exercise-induced analgesia.

One-hour exposure to moderate illuminance (500 lux) shifts the human melatonin rhythm

Abstract: Salivary melatonin levels were measured in 12 healthy volunteers in order to determine whether a moderate light intensity, which suppresses the nocturnal rise of melatonin, was able to shift the melatonin rhythm. The samples were collected at 1‐hr intervals under lighting of < 100 lux (experiment 1) or < 10 lux (experiment 2). The control melatonin profiles were determined during the first night. In the second night the subjects were exposed to light of 500 lux for 60 min during the rising phase of melatonin synthesis. The third series of samples was collected during the third night. The mean decrease of melatonin levels by the exposure to light was 56% of the prelight concentrations. The melatonin onset times were delayed significantly (about 30 min) the night after the exposure to light. The melatonin offset times tended to be delayed in experiment 2. The shifts of the melatonin offset correlated positively with the amount of the melatonin suppression. The results suggest that a relatively small and short lasting light‐induced interruption of melatonin synthesis may affect the melatonin rhythm in humans.

Twenty-Four-Hour Rhythms in Relation to the Natural Photoperiod: A Field Study in Humans

The daily rhythms of salivary melatonin, salivary cortisol, and axillary body temperature were measured in nine healthy volunteers in midsummer, around the autumn equinox, and in midwinter, at a latitude of 60°N. The aim was to find out whether these rhythms were dependent on variations of the natural daylength. The samples were collected every 2 hr during 24-hr periods in everyday conditions. The individual rhythms were characterized with the acrophase estimates of the best-fitting cosine curve models and with the half-rise and half-decline times calculated from the raw data. The melatonin and cortisol rhythms were delayed significantly (about 1 hr) in midwinter as compared with summer and autumn. The most advanced rhythms were found in autumn. The shifts of the melatonin and cortisol rhythms could be explained as a result of the changes of natural illumination. The overt temperature rhythms did not differ significantly among the sampling months. The lack of seasonal patterns in temperature rhythms probably primarily reflected the socially determined rest-activity cycles of the subjects.

Melatonin, cortisol and body temperature rhythms in Lennox-Gastaut patients with or without circadian rhythm sleep disorders.

The daily rhythms of melatonin, cortisol and body temperature were studied in 16 institutionalized subjects with the Lennox-Gastaut syndrome. The results of 9 subjects with normal daily rhythms of sleep and wakefulness (group 1) were compared with those of 7 subjects with disordered sleep (group 2). Salivary samples were collected and axillary temperature was measured every 2 h during two or three separate 26-h periods. The hormones were measured by radioimmunoassays. The rhythms were characterized with single cosinor analysis. Two subjects in group 1 and six subjects in group 2 had abnormalities in their rhythms of temperature, cortisol or melatonin. All three rhythms were disrupted in two subjects of group 2. These two subjects were the only ones with disrupted cortisol rhythm. The diversity of rhythm pathologies suggested partly separate regulatory mechanisms for each rhythm. The co-occurrence of circadian rhythm sleep disorders with the deteriorated melatonin rhythm raised the question as to whether the sleep disorders of these subjects, like those of subjects with healthy brains, could be relieved by the induction of normal melatonin rhythm.

Exogenous melatonin fails to counteract the light-induced phase delay of human melatonin rhythm

Salivary melatonin levels were measured in 6 healthy volunteers in order to determine whether the phase shift caused by a single 60-min light pulse of 2000 lux might be inhibited by maintaining high melatonin concentration. In the control sessions, the samples were collected at 60-min intervals under lighting of < 10 lux from 18.00 to 11.00 h. In the light-exposure sessions, placebo or 0.5 mg melatonin was administered orally 60 min prior to the light pulse, timed at the rising phase of the melatonin synthesis. The after-light sessions, one day after the light exposure, were like the control sessions. The average delays of the melatonin half-rise and half-decline times were equal (about 0.7 h) in the placebo and melatonin replacement experiments. The maintenance of high melatonin levels during the light exposure did not counteract the influence of bright light on the melatonin rhythm. Thus, in the adjustment of the melatonin rhythm, light is a stronger regulator than melatonin itself.

Interindividual Differences in the Responses of Serum and Salivary Melatonin to Light

Several studies in the late seventies characterized insensitivity to light as a feature of human melatonin synthesis. Later it has shown that bright light does suppress human melatonin secretion (Lewy et al. 1980). More recently it has been reported that even lower illuminances decrease the nighttime melatonin levels in humans (e.g. Bojkowski et al. 1987, McIntyre et al. 1989a). Technical and experimental differences may serve as an explanation for the deviating results. It is also possible that interindividual differences of sensitivity obtained from small groups of subjects distort the results. In the present preliminary study we attempted to find such individual differences.

Locomotor activity and melatonin rhythms in rats under non-24-h lighting cycles

The adjustment of pineal melatonin and locomotor activity rhythms to 10:10-h light:dark (LD) or 14:14-h LD cycles was studied in male Wistar rats. Both lighting conditions were thought to be outside the limits of entrainment of the rest-activity rhythm in this species. We assumed that the rhythm of pineal melatonin synthesis might be more adaptable. As expected, the locomotor activity rhythm was not adjusted to the 10:10-h LD cycles. Under these conditions, a free-running component (25 h) became dominant. Under the 14:14-h LD cycles, however, an unexpected adaptation occurred within 10 days. The profiles of the pineal melatonin contents measured on days 5 and 30 under the 10:10-h LD and on day 7 under the 14:14-h LD schedule were in line with the estimated free-running oscillations, but the profile on day 21 under the 14:14-h LD schedule was not. This melatonin pattern fitted the LD-adjusted activity rhythm. Thus, the melatonin rhythm did not adapt better than the activity rhythm to the exotic LD cycles. Instead, parallel changes were found.

Daytime dark exposure increases pineal melatonin in rat pups

Abstract: Photic regulation of the pineal melatonin synthesis was studied in 3‐ to 21‐day‐old rat pups by exposing the animals to light at night (30–40 min) or to darkness during the day (30–240 min). The pineal melatonin contents were measured by radioimmunoassay. A significant day/night difference in the melatonin content and the nocturnal light‐induced decrease were not found until second postnatal week. A novel finding was that at the age of 13–17 days a daytime dark exposure elevated the pineal melatonin content; it was twofold as compared with the normal daytime level and about half of the nocturnal peak level. In 21‐day‐old rats the response had disappeared, while the nocturnal suppression by light persisted. The dark‐induced increase of the melatonin synthesis was independent of the opening of the eyelids which occurs in pups at the age of two weeks, but it was greater in maternally isolated than non‐isolated pups. The results suggest that one component of the circadian regulatory system matures at the end of the third postnatal week. This mechanism inhibits the elevation of the melatonin synthesis by darkness during the daytime.

REM sleep deprivation increases early morning pineal melatonin in castrated rats.

Recently nighttime melatonin levels have been shown to be attenuated in depressive patients or patients with dementia of the Alzheimer type. On the other hand, depression can be transiently relieved by deprivation of rapid eye movement sleep. Since exogenous melatonin administration increases rapid eye movement sleep and slow wave sleep in the rat, could rapid eye movement sleep deprivation then inversely influence endogenous melatonin production? We found indices that in castrated Wistar rats 4 days of rapid eye movement sleep deprivation by the cuff pedestal method elevates the pineal content of melatonin by a factor of two at 1 to 2 h after light onset. Rapid eye movement sleep is thus suggested to influence pineal activity. This mechanism might be involved in the human depression-alleviating effect of rapid eye movement sleep deprivation.

Uncoupling of the pineal melatonin synthesis of rats from the circadian regulation

We show that the pineal melatonin synthesis of rats can be uncoupled from the circadian regulation by exposing the animals to abnormally long light periods. Male rats were kept 7 days under 22.5/1.5-h light/dark conditions and then exposed to darkness at different times of the day. After a 60-min dark exposure, the melatonin synthesis increased independently of the time of the day (Expt. 1). During 22 h in darkness, the mean melatonin content did not return to the low daytime level (Expt. 2). A dark-induced, time-independent increase of melatonin was also found after the rats had been 3-7 days under constant light (Expts. 3 and 4).