Slow brushing reduces heat pain in humans.

BACKGROUND: C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. METHODS: In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. RESULTS: Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. CONCLUSIONS: Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms. SIGNIFICANCE: Slow brushing stimuli - optimal for activation of C-tactile fibres - can reduce pain from cutaneous heating. No such effect was seen with fast brushing or vibration. These observations indicate the role of C-tactile fibres in pain modulation.

Interpersonal stroking touch is targeted to C tactile afferent activation.

C tactile fibers are a specialized group of fibers innervating the non-glabrous skin that are tuned to light gentle stroking applied with velocities between 1 and 10 cm/s. Those fibers add to the sensation of interpersonal caressing and pleasant touch. It is unclear whether people spontaneously apply touch that is tuned to optimally activate those fibers. This was investigated in three studies. In study one, 45 participants (21.8 ± 2.3 years, 24 women) were asked to stroke an artificial arm. In study two, 32 participants (28.3 ± 8.7 years, 16 women) were asked to stroke their partner. In study three, 11 parents (29.4 ± 5.7 years, 6 women) were asked to stroke their babies. Stroking velocity was tracked in all conditions. Stroking velocities were significantly slower in the partner touch and baby touch condition than in the artificial arm condition and all of the participants stroking their partner or baby used velocities that can activate C tactile fibers. We conclude that human social stroking is optimized for C tactile stimulation.

Energy expenditure by multisensor armband in overweight and obese lactating women validated by doubly labeled water.

OBJECTIVE: To validate total energy expenditure (TEE) and activity energy expenditure (AEE) from the portable SenseWear armband (SWA) Pro 2 (TEESWA and AEESWA ; InnerView software versions SWA 5.1 and SWA 6.1) against TEE from doubly labeled water (DLW) and AEE from DLW and indirect calorimetry (TEEDLW and AEEDLW ) in overweight/obese lactating women at 10 weeks postpartum. DESIGN AND METHODS: TEE was measured simultaneously with DLW (14 days) and SWA (first 7 days). Lactating women (n = 62), non-smoking, with a BMI > 25 kg/m(2) and wearing time SWA ≥ 90% were included. RESULTS: Mean TEESWA5.1 was overestimated with 85 kcal/day compared to TEEDLW (P = 0.040), while mean TEESWA6.1 was underestimated with 241 kcal/day compared to TEEDLW (P < 0.001). Mean AEESWA5.1 was similar to mean AEEDLW (P = 0.818), while mean AEESWA6.1 was underestimated with 581 kcal/day compared to AEEDLW (P < 0.001). TEESWA6.1 and AEESWA6.1 were systematically underestimated at higher levels of energy expenditure and BMI while only AEESWA5.1 was systematically overestimated at higher levels of energy expenditure. CONCLUSIONS: TEESWA5.1 and AEESWA5.1 were fairly estimated on a group level while TEESWA6.1 and AEESWA6.1 were significantly and systematically underestimated. Both SWA software versions showed large individual variation in agreement with TEEDLW and AEEDLW , limiting the validity on individual level.

Touching and feeling: differences in pleasant touch processing between glabrous and hairy skin in humans.

Previous functional magnetic resonance imaging studies in two rare patients, together with microneurography and psychophysical observations in healthy subjects, have demonstrated a system of mechanosensitive C-fiber tactile (CT) afferents sensitive to slowly moving stimuli. They project to the posterior insular cortex and signal pleasant aspects of touch. Importantly, CTs have not been found in the glabrous skin of the hand, yet it is commonly observed that glabrous skin touch is also perceived as pleasant. Here we asked if the brain processing of pleasant touch differs between hairy and glabrous skin by stroking the forearm and glabrous skin of the hand during positron emission tomography. The data showed that, when contrasting slow brush stroking on the forearm with slow brush stroking on the palm, there were significant activations of the posterior insular cortex and mid-anterior orbitofrontal cortex. The opposite contrast showed a significant activation of the somatosensory cortices. Although concurrent psychophysical ratings showed no differences in intensity or pleasantness ratings, a subsequent touch questionnaire in which subjects used a newly developed 'touch perception task' showed significant difference for the two body sites. Emotional descriptors received higher ratings on the forearm and sensory descriptors were rated more highly on the palm. The present findings are consistent with the hypothesis that pleasant touch from hairy skin, mediated by CT afferents, is processed in the limbic-related cortex and represents an innate non-learned process. In contrast, pleasant touch from glabrous skin, mediated by A-beta afferents, is processed in the somatosensory cortex and represents an analytical process dependent on previous tactile experiences.

Feeling good: on the role of C fiber mediated touch in interoception.

The human skin is innervated by a network of thin, slow-conducting afferent (C and Aδ) fibers, transmitting a diverse range of information. Classically, these fibers are described as thermo-, noci- or chemoreceptive, whereas mechanoreception is attributed exclusively to thick, fast-conducting (Aß) afferents. A growing body of evidence, however, supports the notion that C tactile afferents comprise a second anatomically and functionally distinct system signaling touch in humans. This review discusses established as well as recent findings which highlight fundamental differences in peripheral and central information coding and processing between Aß and C mechanoreception. We conclude that from the skin through the brain, C touch shares more characteristics with interoceptive modalities (e.g. pain, temperature, and itch) than exteroceptive Aß touch, vision or hearing. In this light, we discuss the motivational-affective role of C touch as an integral part of a thin-fiber afferent homeostatic network for the maintenance of physical and social well-being.

Tactile direction discrimination and vibration detection in diabetic neuropathy.

OBJECTIVE: To evaluate the clinical usefulness of quantitative testing of tactile direction discrimination (TDD) in patients with diabetic neuropathy. MATERIALS AND METHODS: TDD and vibration detection were examined on the dorsum of the feet in 43 patients with type 1 diabetes mellitus and clinical signs and symptoms indicating mild neuropathy, and abnormal results for neurography, temperature detection, or heart rate variability. Test-retest examination of TDD was performed in nine of the patients. RESULTS: Twenty-six of the patients had abnormal TDD (sensitivity 0.60) and 20 had abnormal vibration detection (sensitivity 0.46). Ten of the patients had abnormal TDD and normal vibration detection. Four of the patients had abnormal vibration detection and normal TDD. Test-retest examination of TDD showed a high degree of reproducibility (r = 0.87). CONCLUSION: TDD seems more useful than vibration detection in examination of diabetic neuropathy.

Longitudinal study of the maternal insulin-like growth factor system before, during and after pregnancy in relation to fetal and infant weight.

BACKGROUND: The maternal insulin-like growth factor (IGF) system is considered to be involved in fetal growth regulation. However, available data linking this system to fetal growth are contradictory and incomplete. AIMS: To measure components of the IGF system before, during and after pregnancy in healthy women and to relate these results, and their changes during pregnancy, to fetal weight (gestational week 31) and birth weight. METHODS: Serum concentrations of IGF-I, IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3 and IGFBP-3 protease activity were assessed in 23 women before conception, at weeks 8, 14, 20, 32 and 35 of pregnancy and 2 weeks postpartum. The data were analyzed using simple and multiple linear regression. RESULTS: One third of the variability in fetal weight was explained by IGF-I in combination with IGFBP-3 protease activity, both assessed at gestational week 32 (p = 0.013). Birth weight was negatively correlated (r = -0.43 to -0.59) with IGFBP-1 at gestational week 20 (p = 0.041), 32 (p = 0.012) and 35 (p = 0.003). CONCLUSION: We propose there is a finely tuned balance among the components of the IGF system, providing a means for fetal growth regulation.

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.

Tactile functions after cerebral hemispherectomy.

Patients that were hemispherectomized due to brain lesions early in life sometimes have remarkably well-preserved tactile functions on their paretic body half. This has been attributed to developmental neuroplasticity. However, the tactile examinations generally have been fairly crude, and subtle deficits may not have been revealed. We investigated monofilament detection and three types of tactile directional sensibility in four hemispherectomized patients and six healthy controls. Patients were examined bilaterally on the face, forearm and lower leg. Normal subjects were examined unilaterally. Following each test of directional sensibility, subjects were asked to rate the intensity of the stimulation. On the nonparetic side, results were almost always in the normal range. On the paretic side, the patients' capacity for monofilament detection was less impaired than their directional sensibility. Despite the disturbed directional sensibility on their paretic side the patients rated tactile sensations evoked by the stimuli, on both their paretic and nonparetic body halves, as more intense than normals. Thus, mechanisms of plasticity seem adequate for tactile detection and intensity coding but not for more complex tactile functions such as directional sensibility. The reason for the high vulnerability of tactile directional sensibility may be that it depends on spatially and temporally precise afferent information processed in a distributed cortical network.

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.

Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.

Long-term modulation by postnatal oxytocin of the alpha 2-adrenoceptor agonist binding sites in central autonomic regions and the role of prenatal stress.

The aim of this work was to evaluate whether oxytocin administered in male rats subcutaneously early in life in the absence or presence of food restriction during pregnancy has life-long effects on the alpha(2)-agonist binding sites in the nucleus of the solitarii tract (NTS), in the hypothalamus and the amygdala, as evaluated by quantitative receptor autoradiography. Maternal food restriction alone increased the affinity of the alpha(2)-agonist [(3)H]UK14.304 binding sites exclusively in the NTS. In offspring from ad libitum fed dams, oxytocin treatment significantly increased the density of alpha(2)-agonist binding sites in the NTS and in the hypothalamus. The K(d) value of the alpha(2)-agonist binding sites in the hypothalamus of these rats, but not in the other regions studied, was also significantly increased. In offspring from food-restricted dams, oxytocin treatment produced a significant increase of the B(max) values in the hypothalamus and the amygdala and the K(d) value of the alpha(2)-agonist binding sites in the NTS of these rats also was selectively and significantly increased. These results suggest that a postnatal, oxytocin-induced increase of regional alpha(2)-adrenoceptor function can be seen in adulthood by a persistent, regionally selective increase in the density of central alpha(2)-adrenoceptor agonist binding sites, in the absence of an affinity change in the NTS. Such a regional increase of alpha(2)-adrenoceptor signalling in adulthood may contribute to the anti-stress action of postnatal oxytocin. By contrast, after prenatal stress, the potential increase in alpha(2)-adrenoceptor signalling takes place via selective increases of density with no changes of affinity of the alpha(2)-agonist binding sites in the hypothalamus and the amygdala.

Effects of food restriction and pregnancy on the expression of insulin-like growth factors-I and -II in tIssues from guinea pigs.

The insulin-like growth factor (IGF) system is subjected to pregnancy-associated changes in the circulation and is suggested to be of importance for partitioning of nutrients between the mother and the foetus. Interestingly, maternal undernutrition alters the pregnancy-associated changes, with possible adverse consequences for the mother and the foetus. However, it is not known how malnutrition and pregnancy alter the expression of mRNA for IGFs locally in different tIssues. The aims of this study were to investigate where IGF-I and IGF-II are expressed in guinea pigs and how this expression is altered during food restriction and pregnancy. Ad libitum-fed and food-restricted (fed 70% of the ad libitum-fed intake four weeks before pregnancy and throughout the study) guinea pigs were mated. On day 40 of pregnancy and on the corresponding day for virginal females the animals were killed. mRNA for IGF-I and IGF-II was analysed in various organs/tIssues by solution hybridisation. mRNA for IGF-I was expressed in high amounts in uterus, liver and adipose tIssues. The expression was not affected by food restriction, but was increased in liver and adipose tIssue and decreased in uterus by pregnancy. mRNA for IGF-II was expressed in high amounts in the placenta and liver. In the placenta the expression was decreased by food restriction. Pregnancy increased the levels of mRNA for IGF-II in the liver. Food-restricted dams had smaller foetuses and placentas. In conclusion, this study indicates an important role for the adipose tIssue during gestation, not only as an energy store but also as an endocrine tIssue expressing IGF-I. The decreased expression of IGF-II in the placenta due to food restriction is suggested to have adverse effects on placental structure and function.

Unmyelinated tactile afferents signal touch and project to insular cortex.

There is dual tactile innervation of the human hairy skin: in addition to fast-conducting myelinated afferent fibers, there is a system of slow-conducting unmyelinated (C) afferents that respond to light touch. In a unique patient lacking large myelinated afferents, we found that activation of C tactile (CT) afferents produced a faint sensation of pleasant touch. Functional magnetic resonance imaging (fMRI) analysis during CT stimulation showed activation of the insular region, but not of somatosensory areas S1 and S2. These findings identify CT as a system for limbic touch that may underlie emotional, hormonal and affiliative responses to caress-like, skin-to-skin contact between individuals.

Tactile directional sensibility and diabetic neuropathy.

Five different procedures used to diagnose neuropathy were compared in a "blind" study with diabetic patients. The aim was to evaluate tests of tactile directional sensibility. Three matched groups were examined, two groups with type I diabetes, either with or without suspected neuropathy, and one of healthy controls. Testing consisted of: (1) examination by a specialist in neurology, (2) electrophysiologic measurement of nerve conduction velocity and determination of cool sensitivity, and (3) determination of directional sensibility in two stages, with categorical and quantitative techniques. Abnormal test results were obtained for both groups of diabetic patients. Quantitatively measured directional sensibility had the highest sensitivity (89%) and specificity (85%) when calculated for patients who had received a diagnosis of neuropathy from the neurologist, despite one case of abnormal directional sensibility among the healthy controls. Conduction velocity testing was almost comparably sensitive (80%) and cool sensitivity, comparably specific (85%) when calculated in the same manner.

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

Cortical activation by tactile and painful stimuli in hemispherectomized patients.

Hemispherectomized patients are able to perceive tactile and painful stimuli on their nonparetic as well as paretic body halves. We have used functional MRI to study the cortical mechanisms underlying this preserved somatosensory capacity. Nonpainful brushing and painful heat were applied to the skin of the legs in four hemispherectomized patients and, for comparison, in four normal subjects. Cortical activation was studied with a 1.5 T scanner using a BOLD (blood oxygen level dependent) protocol. All patients rated both the brushing and the heat pain as almost equally intense on each leg and the ratings were similar to those in normals. Brushing on the nonparetic leg activated primary and secondary somatosensory cortices (S1 and S2) in all patients, similar to findings in normals. Brushing on the paretic leg activated S1 in two patients and S2 in one of these patients. Heat pain activated S2, insular cortex and anterior cingulate cortex to a similar degree for both legs, but the activation was weaker in the patients than in the normals. For the individual patient, there was generally no obvious correlation between cortical activation as studied with the BOLD technique and psychophysical performance. The findings from tactile stimulation of the nonparetic leg, that the activation was similar to the contralateral activation in normals, suggest that tactile information processing in the hemisphere contralateral to the stimulation is independent of the corpus callosum. In contrast, the pain activation for the nonparetic leg was weaker than in normals, suggesting that pain activation in the hemisphere contralateral to the stimulation is dependent on transcallosal information processing. The latter finding was corroborated by a subnormal capacity for pain localization on the nonparetic foot in two of the patients. The findings from stimulation of the paretic leg show that areas typically involved in the processing of tactile and painful stimuli can be activated by ipsilateral pathways directly from the periphery. The tactile-evoked ipsilateral S1 activation may be due to subcortical reorganization, since it was not observed in the normal subjects.

Tactile directional sensibility: peripheral neural mechanisms in man.

Tactile directional sensibility, i.e. the ability to tell the direction of an object's motion across the skin, is an easily observed sensory function that is highly sensitive to disturbances of the somatosensory system. Based on previous psychophysical experiments on healthy subjects it was concluded that directional sensibility depends on two kinds of information from cutaneous mechanoreceptors; spatio-temporal information and information about friction-induced changes in skin stretch. In the present study responses to similar probe movements as in the psychophysical experiments were recorded from human single mechanoreceptors in the forearm skin. All slowly adapting type 2 (SA2) units were spontaneously active, and with increasing force of friction their discharge rates were modified by probe movements at increasing distances from the Ruffini end-organ, reflecting the high stretch-sensitivity of these units. Slowly adapting type 1 (SA1) and field units responded to the moving probe within well-defined skin areas directly overlying the individual receptor terminals, and compared to the SA2 units their response properties were less dependent on the force of friction. The results suggest that SA1 and field units have the capacity to signal spatio-temporal information, whereas a population of SA2 units have the capacity to signal direction-specific information about changes in lateral skin stretch.

Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin.

Impulses were recorded from unmyelinated afferents innervating the forearm skin of human subjects using the technique of microneurography. Units responding to innocuous skin deformation were selected. The sample (n = 38) was split into low-threshold units (n = 27) and high-threshold units (n = 11) on the basis of three distinctive features, i.e., thresholds to skin deformation, size of response to innocuous skin deformation, and differential response to sharp and blunt stimuli. The low-threshold units provisionally were denoted tactile afferents on the basis of their response properties, which strongly suggest that they are coding some feature of tactile stimuli. They exhibited, in many respects, similar functional properties as described for low-threshold C-mechanoreceptive units in other mammals. However, a delayed acceleration, not previously demonstrated, was observed in response to long-lasting innocuous indentations. It was concluded that human hairy skin is innervated by a system of highly sensitive mechanoreceptive units with unmyelinated afferents akin to the system previously described in other mammals. The confirmation that the system is present in the forearm skin and not only in the face area where it first was identified suggests a largely general distribution although there are indications that the tactile C afferents may be lacking in the very distal parts of the limbs. The functional role of the system remains to be assessed although physiological properties of the sense organs invite to speculations that the slow tactile system might have closer relations to limbic functions than to cognitive and motor functions.

Remarkable capacity for perception of the direction of skin pull in man.

We determined the ability to appreciate the direction of a skin pull caused by a moving pin that was glued to the forearm skin. A majority of the subjects were able to tell the direction of pin movements with an excursion of 0.13 mm (>/=66% correct responses, p<0.05). Local skin anaesthesia showed that stretch sensitive receptors located over 15 mm in front and behind the pin correctly signalled the direction of these minute skin pulls. It was concluded that information about patterns of skin stretch is an important component of the somatosensory system that may contribute not only to kinaesthetic, but also to cutaneous sensations.