Effect of environment on the long-term consequences of chronic pain.

Much evidence from pain patients and animal models shows that chronic pain does not exist in a vacuum but has varied comorbidities and far-reaching consequences. Patients with long-term pain often develop anxiety and depression and can manifest changes in cognitive functioning, particularly with working memory. Longitudinal studies in rodent models also show the development of anxiety-like behavior and cognitive changes weeks to months after an injury causing long-term pain. Brain imaging studies in pain patients and rodent models find that chronic pain is associated with anatomical and functional alterations in the brain. Nevertheless, studies in humans reveal that lifestyle choices, such as the practice of meditation or yoga, can reduce pain perception and have the opposite effect on the brain as does chronic pain. In rodent models, studies show that physical activity and a socially enriched environment reduce pain behavior and normalize brain function. Together, these studies suggest that the burden of chronic pain can be reduced by nonpharmacological interventions.

Feelings of warmth correlate with neural activity in right anterior insular cortex.

The neural coding of perception can differ from that for the physical attributes of a stimulus. Recent studies suggest that activity in right anterior insular cortex may underlie thermal perception, particularly that of cold. We now examine whether this region is also important for the perception of warmth. We applied cutaneous warm stimuli on the left leg (warmth) in normal subjects (n = 7) during functional magnetic resonance imaging (fMRI). After each stimulus, subjects rated their subjective intensity of the stimulus using a visual analogue scale (VAS), and correlations were determined between the fMRI signal and the VAS ratings. We found that intensity ratings of warmth correlated with the fMRI signal in the right (contralateral to stimulation) anterior insular cortex. These results, in conjunction with previous reports, suggest that the right anterior insular cortex is important for different types of thermal perception.

Effect of isoflurane on the auditory steady-state response and on consciousness in human volunteers.

BACKGROUND: The auditory steady state response (ASSR) is a sustained electrical response of the brain to auditory stimuli delivered at fast rates (30-50 responses/s). The aim of this study was to evaluate the effect of 0.26-0.50% isoflurane on the ASSR and on consciousness, defined as responsiveness to verbal commands. METHODS: Ten volunteers (21-31 yr) participated. Isoflurane was administered at three stable, end-tidal concentrations: 0.26%, 0.38%, and 0.50%. The ASSR in response to 18,000 stimuli (500-Hz tonebursts, 10 ms, 82-dB, the right ear, 35-45 bursts/s) was recorded from the vertex with reference to the right mastoid. Recordings were made during baseline, at each isoflurane concentration, and during recovery. RESULTS: The mean (SD) ASSR amplitudes were 0.32 (0.23) microV during baseline, 0.24 (0.17) microV during 0.26% isoflurane, 0.09 (0.05) microV during 0.38% isoflurane, 0.04 (0.03) microV during 0.50% isoflurane, and 0.29 (0.33) microV during recovery. The amplitude during baseline and recovery was larger than during 0.38% and 0.50% isoflurane (P < 0.001). The amplitude at 0.26% was larger than at the other concentrations (P < 0.025). The logarithm of the ASSR amplitude was related linearly to the concentration of isoflurane (r = 0.85; P < 0.0001). The prediction probability (Pk) for loss of consciousness was 0.95 for both ASSR and measured isoflurane concentration. An ASSR amplitude < 0.07 microV was always associated with unconsciousness. CONCLUSIONS: The ASSR is attenuated in a concentration-dependent manner by isoflurane. Suppression of consciousness and maximal attenuation of ASSR occur in the same isoflurane concentration range. Profound attenuation of ASSR appears to reflect unconsciousness, defined as unresponsiveness to verbal commands.

Comparison of the effects of enflurane/N2O on the 40-Hz auditory steady-state response versus the auditory middle-latency response.

The auditory middle-latency response (AMLR) is a sequence of negative-positive waves occurring 12-50 ms after the onset of an auditory stimulus presented at rates of 10/s or less. When the rate of stimulus presentation is increased to approximately 40/s, overlapping of the AM-LRs results in a sustained, nearly sinusoidal wave, called the "40-Hz auditory steady-state response" (40-Hz ASSR). The AMLR and 40-Hz ASSR have been used to study the effects of general anesthetics on the brain. The primary aim of this investigation was to determine whether the effects of a general anesthetic, namely enflurane, on the 40-Hz ASSR can be predicted from its effects on the AMLR. A secondary aim was to examine the relationship between the level of consciousness and the 40-Hz ASSR during emergence from anesthesia. Twelve ASA class I-II women undergoing reduction mammoplasty were tested. Anesthesia was induced with fentanyl (3 micrograms/kg) and thiopental (3-5 mg/kg) intravenously and was maintained with enflurane (0.5%, 0.8%, or 1.1% end-tidal; four patients per concentration; random assignment) in N2O (66% end-tidal), along with fentanyl (1 microgram/kg as needed). The 40-Hz ASSR and AMLR were recorded before induction and during anesthesia and surgery. The 40-Hz ASSR was also recorded during emergence. The amplitude of the 40-Hz ASSR was reduced profoundly during anesthesia and surgery (P < 0.001). The attenuation was not dose-dependent, and was much more pronounced than predicted by the effects of enflurane on the AMLR. The 40-Hz ASSR during anesthesia was surprisingly large (0.09 and 0.11 microV) in two patients, both of the 1.1% enflurane group. The regaining of the ability to follow verbal commands was associated with a significant (P < 0.001) increase in the amplitude of the 40-Hz ASSR. We conclude that, although auditory neurons remain capable of responding at a slow stimulus rate during enflurane-N2O anesthesia, their ability to be driven at a faster stimulus rate is markedly curtailed. The 40-Hz ASSR may be useful for detecting unintentional intraoperative awareness because the return of consciousness is associated with a clear increase in amplitude.

The P3a wave of the auditory event-related potential reveals registration of pitch change during sufentanil anesthesia for cardiac surgery.

BACKGROUND: The N1 and P3 waves of the auditory event-related potential provide information on consciousness and cortical function. The N1 wave is reduced during states of low vigilance. The P3 wave occurs only for stimuli that somehow capture the subject's attention. There are two types of P3:P3a and P3b. The P3a predominates frontally and probably occurs when the subject simply notices the stimulus. The P3b predominates parietally and indicates conscious awareness of the evoking stimulus. The N1 and P3 were recorded in 12 patients during cardiac surgery under sufentanil anesthesia to search for unintentional awareness. The study was limited to the period before cardiopulmonary bypass. METHODS: After premedication with diazepam, morphine, and scopolamine, sufentanil was used for induction (mean dose, 7.9 micrograms/kg) and maintenance (4 micrograms/kg) of anesthesia. No other anesthetics were administered. Recordings were obtained before induction, during induction after loss of consciousness, after tracheal intubation before incision, and before cardiopulmonary bypass. RESULTS: The N1 was attenuated significantly by sufentanil but was not abolished. The P3b occurred only during preinduction. There was no P3 during induction. There was a P3a during postintubation and precardiopulmonary bypass. CONCLUSIONS: The attenuation of N1 from induction onward reflects a decrease in the level of arousal caused by sufentanil. A P3a during postintubation and precardiopulmonary bypass indicates that pitch discrimination at the cortical level occurs but does not prove that conscious awareness has occurred. Whether or not the P3a reflects the regaining of consciousness is not known.

Number of mice per cage influences uncoupling protein content of brown adipose tissue.

The effect of housing density of mice on the thermogenic state and capacity of their brown adipose tissue was studied. Mice were housed one, two, or six per cage at 28 degrees C for 15 days. Increased housing density suppressed the thermogenic capacity of brown adipose tissue (decreased the total amount of uncoupling protein) and decreased the thermogenic state of brown adipose tissue mitochondria (decreased GDP binding). A density of six mice per cage had a greater effect than a density of two mice per cage. The size of brown adipose tissue (wet weight and protein content), the content of mitochondria in it (cytochrome oxidase content), and the total activity of thyroxine 5'-deiodinase were not altered by housing density. We conclude that even at a temperature close to thermoneutrality (29-33 degrees C for the mouse), the occurrence of social thermoregulation (huddling) reduces the requirement for brown adipose tissue thermogenesis and results in a reduction in its thermogenic capacity. It is clearly of importance that the design of studies of mouse brown adipose tissue take into account not only the temperature at which the mice are housed, but also the number of mice housed per cage.

Aortic stenosis produces hypertrophy of the rat heart without causing an accumulation of N1-acetylspermidine.

Isoprenaline treatment causes cardiac hypertrophy and an accumulation of N1-acetylspermidine in the rat heart. To determine whether the cardiac hypertrophy is the cause of the increase in N1-acetylspermidine, we produced cardiac hypertrophy by constriction of the aorta and analyzed polyamines in the hearts of these rats 1, 3, and 10 days after the aortic constriction. Our results show that compared to sham-operated animals, this treatment caused a 60% increase in putrescine and a 30% increase in spermidine by day 10, but not the expected increase in N1-acetylspermidine. We conclude that N1-acetylspermidine is not induced by a cardiac overload.