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

Single unmyelinated axons in the superficial branch of the peroneal nerve of human subjects were recorded (microneurography) and the response patterns during tonic pressure stimulation (14N at 30 mm(2); 120 s) were assessed using the previously described "marking technique". It was found that tonic pressure stimuli induced augmenting pain responses which were matched by the discharges of initially mechano-insensitive ("silent") C-units, whereas mechano- and heat-responsive "polymodal" C-nociceptors showed a response pattern incompatible with the stimulus-induced perceptions, namely strong initial excitation, followed by adaptation. Eighteen mechano- and heat-responsive "polymodal" C-fibers and 11 mechano-insensitive units were studied. The former had von Frey thresholds <160 mN, the latter were not excited by a von Frey filament of 750 mN (six of them responded to radiant heat stimulation). However, in the course of pressure stimulation, nine of the 11 mechano-insensitive units were activated after more than 20s. A second, identical pressure stimulus induced a stronger response in mechano-insensitive and a weaker response in mechano-responsive units. The stronger response, indicating sensitization, matched the more intense pain perception during the second pressure stimulus. It is concluded that mechano-insensitive C-nociceptors encode pressure-induced pain in human hairy skin and that they play an important role in static mechanical hyperalgesia.
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PMID:Mechano-insensitive nociceptors encode pain evoked by tonic pressure to human skin. 1089 22

Human experimental pain models are important tools in pain research. The primary aims of pain research in normal man is 1) to provide insight in pain mechanisms, 2) to provide a rational basis for clinical trials of pain relieving interventions, and 3) to confirm the anti-nociceptive effects demonstrated in animal models. Most often clinical pain is due to tissue damage leading to acute inflammation and hyperalgesia, but only few human pain models have examined pain responses in injured tissues. Therefore, models with controlled and reversible tissue trauma are needed. The human burn model is an example of such a model, and several groups have performed studies of analgesics and pain mechanisms based on the model. The thesis aims to provide a critical review of the human burn model as a tool in pain research, and to give suggestions for development of the model and future research. The pain and inflammatory responses to superficial thermal burns in skin have been studied in healthy volunteers. Burns have the potential for releasing most of the inflammatory and chemical mediators that produce sensitisation and excitation of nociceptors, and the intense nociceptive input during injury produces sensitisation of central neurones in the nociceptive pathway. Pain and hyperalgesia have been evaluated in the model by thermal, various mechanical, and electrical stimuli. The different methods of pain assessments are discussed to clarify the underlying neural mechanisms, the questions that can be addressed by the measurements, and the discrepancies in results between studies. Inflammation has been evaluated in the model by skin erythema intensity, area of flare, and blister formation. The major determinant of skin erythema intensity is the amount of blood in the most superficial part of the dermis, and burn-induced erythema may be primarily due to congestion of capillary loops and postcapillary venules. The area of flare may be used to evaluate the efferent function of heat-sensitive A delta- and C-fibre nociceptors, whereas blisters may be used to assess edema formation and the degree of injury. Hyperalgesia is induced immediately by the burns and lasts about 24 h dependent on the intensity of the heat stimulus. The burns heal without sequela. A study of the reproducibility of pain assessments in the burn model has shown that measures based on repeated measurements were significantly more reproducible than measures based on single time points. Further, within-day reproducibility was better than between-day reproducibility. Within-day variations of heat pain responses to 45 degrees C and 47 degrees C were smaller than that of pain responses to 43 degrees C, suggesting that assessments using clearly painful stimuli may be more reproducible. A methodological study also demonstrated that habituation to experimental pain developed as the study proceeded. Habituation is common in experimental pain models, and dividing analgesics and placebo evenly between the study days is one way of eliminating the effects of habituation. The use of simultaneous right-left comparisons represents the ideal design when possible. The burn model has been a valuable tool in the study of pain mechanisms. Hyperalgesia to heat in the burned area (primary hyperalgesia) is mediated by sensitisation of C-fibre mechano-heat-sensitive (CMH) nociceptors and A delta-fibre mechano-heat-sensitive (AMH) nociceptors of type I in hairy skin. A contribution from sensitised CNS neurones is likely, and the sensitisation of nociceptors is confined to the injured area. The presence of hyperalgesia to heat in normal skin surrounding a burn (secondary hyperalgesia) has been demonstrated in several studies, but the pain threshold may be unaltered. The mechanisms for primary hyperalgesia to mechanical stimuli may be both peripheral and central, but the importance of peripheral mechanisms is unclear and central mechanisms may account for mechanical hyperalgesia in both the primary and th
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PMID:Inflammatory pain in experimental burns in man. 1091 84

We evaluated evoked potentials (EPs) to noxious contact heat pulses delivered to hairy skin of healthy adults. Heat pulses from an adapting temperature of 34 degrees C to a target temperature of 52 degrees C, produced two scalp positive waves. The first peaked at 44 degrees to 45 degrees C (approximately 500 ms following stimulus onset), while the second peaked approximately 300 ms following the 52 degrees C heat pulse (approximately 1 s after stimulus onset). The first positive wave was absent from an adapting temperature of 39 degrees C, suggesting loss of synchronized activation of warm and/or low threshold mechanothermal afferents. The second EP was observed following stimulation from both adapting temperatures and was associated with subjective report of first pain. Latency difference of the pain EP from arm and leg were consistent with conduction in Adelta nociceptive afferents (approximately 10/ms). EPs to painful contact thermal stimuli may be of value in the evaluation of small fiber peripheral neuropathies and assessment of altered pain states.
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PMID:Somatosensory evoked potentials associated with thermal activation of type II Adelta mechanoheat nociceptive afferents. 1101 76

The recently cloned vanilloid receptor (VR1) is postulated to account for heat and capsaicin sensitivity in unmyelinated afferents. We sought to determine whether heat and capsaicin sensitivity also coexist in myelinated nociceptive afferents. Action potential (AP) activity was recorded from single A-fiber nociceptors that innervated the hairy skin in monkey. Before intradermal injection of capsaicin (10 microg/10 microl) into the receptive field, nociceptors were classified as heat-sensitive (threshold, </=53 degrees C, 1 sec) or heat-insensitive afferents and as mechanically sensitive (von Frey threshold, <6 bar) or mechanically insensitive afferents. All heat-sensitive afferents (n = 16) were insensitive to mechanical stimuli but responded to the intradermal injection of capsaicin (69 +/- 7 APs in 10 min). Responsiveness to mechanical stimuli, thermal stimuli, and capsaicin varied in their receptive fields; the majority of receptive field sites (24 of 36) were responsive to only one or two stimulus modalities, whereas only eight sites responded to all three modalities. For most heat-insensitive afferents, the activity induced by the capsaicin injection did not exceed the activity induced by needle insertion alone. However, the largest response to capsaicin (314 +/- 98 APs in 10 min) was observed for five afferents that were insensitive to heat as well as mechanical stimuli and therefore may be classified as cutaneous chemoreceptors. These results suggest that A-fiber nociceptors play a role in the pain and hyperalgesia associated with capsaicin injection. Our finding that a subgroup of capsaicin-sensitive A-fiber nociceptors are insensitive to heat predicts the existence of heat-insensitive capsaicin receptors.
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PMID:Capsaicin responses in heat-sensitive and heat-insensitive A-fiber nociceptors. 1140 33

Botulinum toxin treatment is an efficient, well-tolerated technique for patients suffering from gustatory sweating, first described by our group. With the experience gained in recent years we were able to improve on some of our skills in the diagnosis and treatment of gustatory sweating and here we wish to focus on some interesting aspects: (1) the necessity for an exact anamnesis before treatment with botulinum toxin to ensure correct treatment; (2) the advantages of Minor's test in special situations, for example, when sweating occurs in regions of hairy skin, retroauricular, at the back of the auricle and in areas distant from the site of salivary gland surgery; (3) the reduction of pain during treatment using an anesthetic ointment containing lidocaine and prilocaine as active substances; (4) intracutaneous injections in areas anterior to the fascia-protected skin of the lateral face-covering mimetic muscles, and (5) the occasional necessity for short-time reinjection in small areas of persistent sweating.
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PMID:Treatment of gustatory sweating with botulinum toxin: special aspects. 1152 73

HIV is a very common infection in Thailand, affecting about one million of the population already, with 99,555 persons with full blown AIDS at the end of 1999. The first case of AIDS was reported in Thailand in 1984. Gastrointestinal involvement is very common, the commonest presentations are diarrhea, esophageal symptoms, hepatobiliary symptoms, and weight loss. When the CD4+ T cell count falls below 200, the body becomes highly susceptible to opportunistic infections and neoplasms. Almost all AIDS patients will have GI symptoms at sometime during the course of their illness. This is because the GI tract contains an abundant quantity of lymphoid tissue and is likely to function as a reservoir of HIV infection. In chronic diarrhea cases, apart from other investigations, small bowel biopsy and aspiration may help to find the cause. If oral candidiasis is present, one should keep HIV in mind and look for oral hairy leucoplakia, dysphagia and odynophagia as one-third of patients with AIDS will develop dysphagia or odynophagia in the course of their disease. Those with esophageal candidiasis will usually have oral candidiasis and odynophagia while 18 per cent of the patients will not have oral thrush. CMV esophagitis and HIV ulcer (or idiopathic oesophageal ulcer) are also common. Upper gastrointestinal endoscopy and biopsy are helpful in finding the exact cause of the oesophageal symptoms. Hepatobiliary manifestations are present with jaundice, hepatomegaly, and pain. ERCP is very helpful in diagnosing and classifying these conditions. Papillary stenosis and dominant biliary stricture can be treated by endoscopy but long term results are still poor due to late manifestation of these conditions.
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PMID:Endoscopy in HIV infected patients. 1152 42

"Synthetic heat", also known as the heat grill illusion, occurs when contact with spatially adjacent warm and cold stimuli produce a sensation of "heat". This phenomenon has been explained as a painful perception that occurs when warm stimulation inhibits cold-sensitive neurons in the spinothalamic tract (STT), which in turn unmasks activity in the pain pathway caused by stimulation of C-polymodal nociceptors (CPNs). The "unmasking model" was tested in experiment 1 by combining warm (35-40 degrees C) and cool (> or = 27 degrees C) stimuli that were too mild to stimulate CPNs. After discovering that these temperatures produced nonpainful heat, experiment 2 was designed to determine whether heat could be induced when near-threshold cooling was paired with mild warmth, and whether lowering the base temperature for cooling would increase the noxious (burning, stinging) components of heat for fixed cooling steps of 1-3 degrees C. Cooling by just 1 degrees C from a base temperature of 33 degrees C led to reports of heat on more than 1/3 of trials, and cooling by just 3 degrees C evoked heat on 75% of trials. Lowering the base temperature to 31 or 29 degrees C increased reports of heat and burning but did not produce significant reports of pain. Perception of nonpainful heat at such mild temperatures indicates either that cold-sensitive nociceptors with thresholds very similar to cold fibers innervate hairy skin in humans, or that heat can result from integration of warm fiber and cold fiber activity, perhaps via convergence on nonspecific (e.g., WDR) neurons in the STT.
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PMID:Synthetic heat at mild temperatures. 1208 87

Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat-induced current (I(heat)) was elicited in six of 13 small DRG neurons (diameter < or =30 microm) tested in the whole-cell configuration of the patch-clamp mode. Current responses in the seven heat-insensitive neurons were within the range explainable by the temperature dependence of the recording setup. I(heat) was characterized by: (1) non-linearity of its amplitude during a suprathreshold heat ramp as well as with stimuli of increasing intensity with an estimated threshold of 42 +/- 1 degrees C; (2) fast rise time and even faster decay time (t(1/2) = 96.5 +/- 5.9 and 27.7 +/- 1.5 ms, respectively); and (3) rate dependence of its induction. All three heat-sensitive neurons tested were also sensitive to capsaicin. The mean threshold for the induction of I(heat) was 2.8 +/- 0.3 J mm(-2). The threshold for the induction of action potentials by depolarizing current pulses was significantly reduced after laser stimulation, suggesting a sensitization at the transformation stage. No such change was seen in heat-insensitive neurons that underwent the same heat stimuli. The same diode laser elicited pain sensations and laser-evoked potentials in human subjects. No significant differences were seen between the pain thresholds in hairy and in glabrous skin, probably due to the deep penetration of this laser radiation. The mean pain threshold for stimuli > or =200 ms in humans was 2.5 +/- 0.2 J mm(-2) (n = 11), and did not differ from the thresholds for the induction of I(heat) in vitro. Our results indicate that I(heat) in primary sensory neurons can be activated by infrared laser pulses that are painful in humans.
Pain 2002 Sep
PMID:Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses. 1223 92

The sympathetic division of the autonomic nervous system is known to play a role in the genesis of neuropathic pain. In the skin of the rat lower lip (hairy skin), sympathetic and parasympathetic fibers normally innervate the same blood vessels in the lower dermis but do not occur in the upper dermis. However, we have shown that sympathetic fiber migration into the upper dermis occurs following mental nerve lesions (Ruocco et al. [2000] J. Comp. Neurol. 422:287-296). As sensory denervation has a dramatic effect on sympathetic fiber innervation patterns in the rat lower lip skin, we decided to investigate the possible changes in the other autonomic fiber type in the skin-the parasympathetic fiber. Sensory denervation of the rat lower lip was achieved by bilateral transection of the mental nerve, and animals were allowed to recover for 1-8 weeks. Lower lip tissue was processed for double-labeling light microscopic immunocytochemistry (ICC), using antibodies against substance P (SP), which labels a subpopulation of peptidergic sensory fibers, and against the vesicular acetycholine transporter (VAChT), as a marker for parasympathetic fibers. In sham-operated rats, SP-immunoreactive (IR) sensory fibers were found in the epidermis and upper and lower dermal regions, whereas VAChT-IR fibers were confined to the lower dermis. Mental nerve lesions induced the gradual disappearance of SP-IR fibers from all skin layers accompanied by the progressive migration of VAChT-IR fibers into the upper dermis. Cholinergic fiber migration was evident by the second week post surgery, and the ectopic innervation of the upper dermis by these fibers persisted even at the last time point studied (8 weeks) when SP-IR fibers have completely regrown. VAChT-IR fibers were observed in the upper dermis, well above the opening of the sebaceous glands into the hair follicles. These results show that considerable changes occur in the innervation patterns of parasympathetic fibers following mental nerve lesions.
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PMID:Parasympathetic nerve fibers invade the upper dermis following sensory denervation of the rat lower lip skin. 1468 74

The Marstock method of limits was used to obtain thresholds for detection of cooling, warming, cold pain and heat pain for 34 young adults, upon eight spatially matched sites on the left and right sides of the face, the right ventral forearm and the scalp. Male and female subjects were tested by both a male and a female experimenter. Neither the experimenter nor the gender of the subject individually influenced the thresholds. The thermal thresholds varied greatly across facial sites: sixfold and tenfold for cool and warmth, respectively, from the most sensitive sites on the vermilion to the least sensitive facial site, the preauricular skin. Warm thresholds were 68% higher than cool thresholds, on average, and 12% higher on the left compared to the right side of the face. The mean cold pain threshold increased from 21.0 degrees C on the hairy upper lip to 17.8 degrees C on the preauricular skin. Sites on the upper lip were also most sensitive to noxious heat with pain thresholds of 42-43 degrees C. The scalp was notably insensitive to innocuous and noxious changes in temperature. For the sensations of nonpainful cool and warmth, the more sensitive a site, the less the estimates of the thresholds differed between subjects. In contrast, for heat pain, the more sensitive a site, the more the estimates differed between subjects. Subjects who were relatively more sensitive to cool tended to be relatively more sensitive to warmth. Subjects' sensitivities to nonpainful cool and warmth were less predictive of their sensitivities to painful cold and heat, respectively. Short-term within-subject variability increased with the magnitude of the thresholds. The lower the threshold, the more similar were repeated measurements of it, within a 5-25 s period.
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PMID:Site-dependent and subject-related variations in perioral thermal sensitivity. 1576 1


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