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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human palm has a lower heat detection threshold and a higher heat pain threshold than hairy skin. Neurophysiological studies of monkeys suggest that glabrous skin has fewer low threshold heat nociceptors (AMH type 2) than hairy skin. Accordingly, we used a temperature-controlled contact heat evoked potential (CHEP) stimulator to excite selectively heat receptors with C fibers or Adelta-innervated AMH type 2 receptors in humans. On the dorsal hand, 51 degrees C stimulation produced painful pinprick sensations and 41 degrees C stimuli evoked warmth. On the glabrous thenar, 41 degrees C stimulation produced mild warmth and 51 degrees C evoked strong but painless heat sensations. We used CHEP responses to estimate the conduction velocities (CV) of peripheral fibers mediating these sensations. On hairy skin, 41 degrees C stimuli evoked an ultra-late potential (mean, SD; N wave latency: 455 (118) ms) mediated by C fibers (CV by regression analysis: 1.28 m/s, N=15) whereas 51 degrees C stimuli evoked a late potential (N latency: 267 (33) ms) mediated by Adelta afferents (CV by within-subject analysis: 12.9 m/s, N=6). In contrast, thenar responses to 41 and 51 degrees C were mediated by C fibers (average N wave latencies 485 (100) and 433 (73) ms, respectively; CVs 0.95-1.35 m/s by regression analysis, N=15; average CV=1.7 (0.41) m/s calculated from distal glabrous and proximal hairy skin stimulation, N=6). The exploratory range of the human and monkey palm is enhanced by the abundance of low threshold, C-innervated heat receptors and the paucity of low threshold AMH type 2 heat nociceptors.
Pain 2005 Jun
PMID:Thermoreceptive innervation of human glabrous and hairy skin: a contact heat evoked potential analysis. 1591 Nov 50

Receptor end organs and free-nerve endings in the skin are the peripheral sentinels of the sensorial nervous system encoding for touch, temperature, and pain. Using a novel approach to analyze the outermost nerves of the skin, we visualized for the first time the distinct microanatomical structure of the touch dome of human hairy skin. The dermal nerve fibers of this slowly adapting type 1 mechanoreceptor were embedded in dermal protrusions that could be readily discerned by Laminin-5 staining. Concerning the nerves supplying the touch domes, we found, unexpectedly, that besides Abeta-fibers, Adelta- and C-fibers also were regularly present. The epidermis overlying the nerve convolutes showed a distinctive architecture of the rete ridges clearly demarcated from the surroundings and extending over 0.193 +/- 0.138 mm(2) (mean +/- standard deviation). Within this area, 756 +/- 386 Merkel cells/mm(2) (mean +/- standard deviation) were present compared with less than 50/mm(2) outside the touch dome, demonstrating for the first time a highly discontinuous distribution of these cells in nonglabrous skin. Our findings strongly suggest that the receptive qualities of human touch domes exceed mechanosensation, and that they may serve as multifunctional nerve end organs in human skin.
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PMID:The touch dome in human skin is supplied by different types of nerve fibers. 1598 29

The localization of the neuropeptide tyrosine (NPY) Y2 receptor (Y2R) protein was studied in mouse dorsal root ganglia (DRGs) and spinal cord, by using a recently developed rabbit anti-Y2R antibody and a sensitive immunohistochemical method. Y2R-like immunoreactivity (-LI) was observed in about 10% of the small/medium-sized lumbar DRG neurons. Among these, about 44% were calcitonin gene-related peptide-immunoreactive, and about 38% bound isolectin B4. In the dorsal horn of the spinal cord, an intense Y2R-LI was seen in the most superficial layers, mostly restricted to laminae I-II. This immunoreactivity was completely abolished by dorsal rhizotomy. Y2R-L1 was also detected on the skin, more abundantly in hairy than glabrous skin. Specificity experiments showed complete disappearance of the Y2R-LI described above after incubation with antibody preadsorbed with the immunogenic peptide. Furthermore, Y2R-LI was also absent in a Y2R knockout mouse. These results demonstrate that the NPY Y2R is associated mainly with both peptidergic and nonpeptidergic small, presumably nociceptive, neurons projecting to the superficial layers of the dorsal horn. The results also support a role for this receptor and NPY in pain mechanisms.
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PMID:Neuropeptide Y2 receptor protein is present in peptidergic and nonpeptidergic primary sensory neurons of the mouse. 1602 47

Complex regional pain syndromes (CRPS, type I and type II) are devastating conditions that can occur following soft tissue (CRPS type I) or nerve (CRPS type II) injury. CRPS type I, also known as reflex sympathetic dystrophy, presents in patients lacking a well-defined nerve lesion, and has been questioned as to whether or not it is a true neuropathic condition with an organic basis. As described here, glabrous and hairy skin samples from the amputated upper and lower extremity from two CRPS type I diagnosed patients were processed for double-label immunofluorescence using a battery of antibodies directed against neural-related proteins and mediators of nociceptive sensory function. In CRPS affected skin, several neuropathologic alterations were detected, including: (1) the presence of numerous abnormal thin caliber NF-positive/MBP-negative axons innervating hair follicles; (2) a decrease in epidermal, sweat gland, and vascular innervation; (3) a loss of CGRP expression on remaining innervation to vasculature and sweat glands; (4) an inappropriate expression of NPY on innervation to superficial arterioles and sweat glands; and (5) a loss of vascular endothelial integrity and extraordinary vascular hypertrophy. The results are evidence of widespread cutaneous neuropathologic changes. Importantly, in these CRPS type I patients, the myriad of clinical symptoms observed had detectable neuropathologic correlates.
Pain 2006 Feb
PMID:Pathologic alterations of cutaneous innervation and vasculature in affected limbs from patients with complex regional pain syndrome. 1678 76

Microneurography is a method using metal microelectrodes to investigate directly identified neural traffic in myelinated as well as unmyelinated efferent and afferent nerves leading to and coming from muscle and skin in human peripheral nerves in situ. The present paper reviews how this technique has been used in clinical neurophysiology to elucidate the neural mechanisms of autonomic regulation, motor control and sensory functions in humans under physiological and pathological conditions. Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task. Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion. Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain. Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch. No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans.
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PMID:Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans. 1690 37

The ability to perceive and withdraw rapidly from noxious environmental stimuli is crucial for survival. When heat stimuli are applied to primate hairy skin, first pain sensation is mediated by type-II A-fibre nociceptors (II-AMHs). In contrast, the reported absence of first pain and II-AMH microneurographical responses when heat stimuli are applied to the hand palm has led to the notion that II-AMHs are lacking in this primate glabrous skin. The aim of this study was to assess the effect of hairy and glabrous skin stimulation on neural transmission of nociceptive inputs elicited by different kinds of thermal heating. We recorded psychophysical and EEG brain responses to radiant (laser-evoked potentials, LEPs) and contact heat stimuli (contact heat-evoked potentials, CHEPs) delivered to the dorsum and the palm of the hand in normal volunteers. Brain responses were analysed at a single-trial level, using an automated approach based on multiple linear regression. Laser stimulation of hairy and glabrous skin at the same energy elicited remarkably similar psychophysical ratings and LEPs. This finding provides strong evidence that first pain to heat does exist in glabrous skin, and suggests that similar nociceptive afferents, with the physiological properties of II-AMHs, mediate first pain to heat stimulation of glabrous and hairy skin in humans. In contrast, when contact heat stimuli were employed, a significantly higher nominal temperature had to be applied to glabrous skin in order to achieve psychophysical ratings similar to those obtained following hairy skin stimulation, and CHEPs following glabrous skin stimulation had significantly longer latencies (N2 wave, +25%; P2 wave, +24%) and smaller amplitudes (N2 wave, -40%; P2 wave, -44%) than CHEPs following hairy skin stimulation. Irrespective of the stimulated territory, CHEPs always had significantly longer latencies (hairy skin N2 wave, +75%; P2 wave, +56%) and smaller amplitudes (hairy skin N2 wave, -42%; P2 wave, -19%) than LEPs. These findings are consistent with the thickness-dependent delay and attenuation of the temperature waveform at nociceptor depth when conductive heating is applied, and suggest that the previously reported lack of first pain and microneurographical II-AMH responses following glabrous skin stimulation could have been the result of a search bias consequent to the use of long-wavelength radiant heating (i.e. CO(2) laser) as stimulation procedure.
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PMID:Similar nociceptive afferents mediate psychophysical and electrophysiological responses to heat stimulation of glabrous and hairy skin in humans. 1697 4

Activation of histamine H3 receptors (H3Rs) reduces inflammation and nociception, but the existence of H3Rs on peripheral innervation has never been demonstrated. Here we use antibodies to locate H3Rs in whisker pads, hairy and glabrous hind paw skin, dorsal root ganglia (DRGs), and spinal cords of rats, wild type mice, and H3R knockout (H3KO) mice. Although H3Rs have been hypothesized to be on C and sympathetic fibers, H3R-like immunoreactivity (H3R-LI) was only detected on presumptive periarterial A delta fibers and on A beta fibers that terminated in Meissner's corpuscles and as lanceolate endings around hair follicles. The H3R-positive periarterial fibers were thin-caliber and coexpressed immunoreactivity for calcitonin gene-related peptide (CGRP), substance P, acid sensing ion channel 3, and 200 kDa neurofilament protein (NF). H3R-LI was also detected on epidermal keratinocytes and Merkel cells, but not on Merkel endings, C fibers, any other A delta fibers, or sympathetic fibers. In DRGs, H3R-LI was preponderantly on medium to large neurons coexpressing NF-LI and mostly CGRP-LI. In dorsal horn, CGRP-positive fibers with and without H3R-LI ramified extensively in lamina II; many of the former formed a plexus in lamina V. Low levels of H3R-LI were also present on A beta fibers penetrating superficial and into deeper laminae. The distribution of H3R-LI was similar in rats and wild type mice, but was eliminated or strongly reduced in A delta fibers and A beta fibers, respectively, in H3KO mice. Taken with recently published behavioral results, the present findings suggest that periarterial, peptidergic, H3R-containing A delta fibers may be sources of high threshold mechanical nociception.
Pain 2007 May
PMID:Immunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord: potential antinociceptive targets. 1713 35

The cortical system underlying perceptual ability to localize tactile and noxious cutaneous stimuli in humans is still incompletely understood. We used transcranial magnetic stimulation (TMS) to transiently interfere with the function of the parietal cortex, at different times after the beginning of noxious or non-noxious mechanical stimulation of the hairy skin overlying the dorsal surface of the first metacarpal of the contralateral hand. Peripheral stimuli consisted of rounded (1mm diameter) or sharp (0.2 mm) metal tips; skin contact lasted on average 242 ms (noxious) and 228 ms (non-noxious). Brief (80 ms, 25 Hz) TMS trains, given at 150 ms after the onset of cutaneous stimulation, significantly impaired subjects' ability in localizing non-nociceptive, tactile input, an effect which was not observed when TMS was applied at 300 ms after cutaneous stimulation. In contrast, brief TMS trains given at 300 ms after the onset of cutaneous stimulation significantly impaired subjects' ability in localizing nociceptive input, an effect which was not observed when TMS was applied at 150 ms after cutaneous stimulation. No impairment in stimulus detection was found in comparison with control sham TMS. The timing of parietal TMS interference with the ability to localize tactile and painful stimuli is compatible with known time differences in the arrival of non-noxious and noxious information in the postcentral gyrus. On these grounds, our findings support the existence of overlapping cortical populations in the contralateral parietal lobe, exerting a role in spatial discriminative aspects of touch and mechanically induced pain.
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PMID:Parietal cortex involvement in the localization of tactile and noxious mechanical stimuli: a transcranial magnetic stimulation study. 1723 52

The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double-blind cross-over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6) was less pleasant (p<0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n=6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low-threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.
Pain 2007 Dec 15
PMID:Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan. 1744 79

The contribution of endothelin-1 (ET-1), acting via endothelin-A receptors (ET(A)), on post-incisional pain was examined in a rat model of incision through the hairy skin of the lumbar dorsum. Post-incisional mechanical hyperesthesia was evaluated by cutaneous trunci muscle reflexes (CTMR) of subcutaneous muscles responding to stimulation with von Frey filaments near the wound (primary responses) and at a distance, especially on the contralateral dorsum (secondary responses, involving spinal circuits). The role of ET(A) was determined by pre-incisional, subcutaneous injection of the selective receptor antagonist BQ-123 at the incision site, 15 min or 24h before surgery. Control incisions showed both primary tactile allodynia and hyperalgesia, and a weaker secondary hyperesthesia, peaking 3-4h after surgery and lasting at least 24h. Primary allodynia, but not hyperalgesia, was dose-dependently suppressed by 15 min pre-incisional BQ-123. In contrast, both secondary allodynia and hyperalgesia were inhibited by local BQ-123. The suppression of primary allodynia by local antagonist disappeared in 24h, but that of secondary hyperesthesia remained strong for at least 24h. Systemically delivered BQ-123 was without effect on any post-incisional hyperesthesia, and if the antagonist was locally injected 24h before surgery there was no difference on hyperesthesia compared to vehicle injected at that time. We conclude that ET-1, released from skin by incision, activates nociceptors to cause primary allodynia and to sensitize spinal circuits through central sensitization. Blockade of ET(A) in the immediate peri-operative period prevents the later development of central sensitization.
Pain 2007 Dec 15
PMID:Cutaneous endothelin-A receptors elevate post-incisional pain. 1746 72


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