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PubMed2000

Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is linked to the human NRAMP1 gene in Vietnamese leprosy sibships.

The Mitsuda test, which measures the specific immune response against intradermally injected lepromin, has a high prognostic value for susceptibility or resistance to the lepromatous form of leprosy. A sib-pair linkage analysis between the Mitsuda response and the NRAMP1 gene was done among 20 nuclear families with leprosy (totaling 118 sibs) from Ho Chi Minh City, Vietnam. All family subjects were genotyped for several intragenic and flanking NRAMP1 markers, leading to the definition of a fully informative NRAMP1 haplotype. Significant linkage was observed between NRAMP1 and Mitsuda reaction when considered either as a quantitative (P<.002) or as a categorical (P=.001) trait. Separate analyses among healthy and affected sibs showed evidence for linkage in both subsamples, indicating that linkage between the Mitsuda reaction and NRAMP1 is independent of leprosy status. These results support the view that NRAMP1 plays a regulatory role for the development of acquired antimycobacterial immune responses as determined by in vivo Mitsuda test reaction.

Carrier Proteins↗
PubMed1997

Activation of the cAMP transduction cascade contributes to the mechanical hyperalgesia and allodynia induced by intradermal injection of capsaicin.

1. The spinal role of the cAMP transduction cascade in nociceptive processing was investigated in awake behaving rats (male, Sprague-Dawley) by activating or inhibiting this pathway spinally. Microdialysis fibres were implanted into the dorsal horn to infuse drugs directly to the spinal cord. 2. Animals, without peripheral tissue injury, were tested for responses to repeated applications (10 trials) of von Frey filaments and threshold to mechanical stimulation before and after infusion of 8-bromo-cAMP. In this group of animals treated spinally with 8-br-cAMP (1-10 mM) a dose-dependent hyperalgesia and allodynia were produced. This was manifested as an increased number of responses to 10 trials of von Frey filaments (10, 50, 150, 250 mN) and a decrease in mechanical threshold. 3. A second series of experiments studied the manipulation of the cAMP pathway spinally in a model of tissue injury induced by intradermal injection of capsaicin. Animals were either pre- or post-treated spinally with the adenylate cyclase inhibitor, tetrahydrofuryl adenine (THFA) or the protein kinase A inhibitor, myrosilated protein kinase (14-22) amide (PKI). Injection of capsaicin resulted in an increased number of responses to repeated applications of von Frey filaments and a decrease in threshold to mechanical stimuli outside the site of injection, secondary mechanical hyperalgesia and allodynia. 4. Pre-treatment with either THFA (1 mM) or PKI (5 mM) had no effect on the capsaicin-evoked secondary hyperalgesia and allodynia. 5. In contrast, post-treatment spinally with THFA (0.01-1 mM) or PKI (0.05-50 mM) dose-dependently reduced the mechanical hyperalgesia and allodynia produced by capsaicin injection. Furthermore, the mechanical hyperalgesia and allodynia blocked by the adenylate cyclase inhibitor, THFA (1 mM), was reversed by infusion of 8-bromo-cAMP (0.01-10 mM) in a dose-dependent manner. 6. Thus, this study demonstrates that activation of the cAMP transduction cascade at the spinal cord level results in mechanical hyperalgesia and allodynia and that the secondary mechanical hyperalgesia and allodynia following intradermal injection of capsaicin is mediated by this same transduction cascade.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

In situ infiltration of natural killer-like cells induced by intradermal injection of the nucleic acid fraction from BCG.

Intradermal injection of MY-1, a nucleic acid fraction extracted from Mycobacterium bovis strain BCG, induced in situ infiltration of mononuclear cells, most of which were asialo GM1 (GA1)-positive as determined by immunofluorescence microscopy. The infiltration occurred with as little as 1 microgram of MY-1 and lasted for a week. Double immunofluorescence microscopy revealed that the infiltrating GA1-positive cells were all positive for Ly-5, and partially positive for Thy-1.2, but negative for Mac-1, Ia, mu-chain, Lyt-1, Lyt-2, L3T4, and Fc receptor II. They contained neither peroxidase nor nonspecific esterase. The infiltrating cells thus markedly resembled natural killer (NK) cells in their cytochemical characteristics and surface markers. DNase and RNase destroyed the GA1-positive cell-inducing activity of MY-1. These results indicate that the nucleic acid components of MY-1 are responsible for this effect.

Animals↗
PubMed1991

Neutrophil recruitment by intradermally injected neutrophil attractant/activation protein-1.

Neutrophil attractant/activation protein-1 (NAP-1) is a recently described cytokine that attracts neutrophils, but not monocytes or eosinophils. This leukocyte specificity is not absolute, in that NAP-1 attracts basophils and small numbers of lymphocytes. Our purpose was to determine in vivo effects of NAP-1, and to compare them to the reported action of the complement attractant, C5a. Intradermal injection into normal human subjects of 40 microliters of NAP-1, over a concentration range of 4 x 10(-8) M to 10(-6) M, caused no symptoms or signs such as wheal-and-flare, itching, induration, or tenderness. However, biopsies of injection sites showed perivascular neutrophil infiltration as early as 30 min, which increased at 1 and 3 h. The mean number of neutrophils per mm2 of dermis for 15 biopsies taken 3 h after intradermal injection of 2 x 10(-7) M or 10(-6) M NAP-1 was 164 +/- 41; the response to saline or a NAP-1 inactive fragment was 5 or less. Intradermal NAP-1 did not cause basophil or lymphocyte infiltration. Consistent with the absence of a wheal-and-flare, acid toluidine blue-stained sections showed no evidence of mast cell degranulation, in contrast to previously reported results with C5a. Thus, the predominant response by human subjects to intradermal NAP-1 was neutrophil accumulation in proximity to dermal blood vessels.

Adolescent↗
PubMedDate not supplied

In vivo gene transfer method in keratinocyte gene therapy: intradermal injection of DNA complexed with high mobility group-1 protein in rats.

In order to develop a more efficient method of introducing genes into keratinocytes in vivo, we intradermally injected DNA bound to high mobility group 1 protein, thereby taking advantages of the naked DNA and hemagglutinating virus of the Japan-liposome method reported previously. First we performed a gel mobility shift assay, which confirmed DNA binding to high mobility group 1. Then we injected beta-galactosidase expression vector complexed with high mobility group 1 into the rat skin and the activity of sample with the protein was 2-3 times higher than that without the protein as control. Semiquantification of transferred-DNA content using polymerase chain reaction and a time course of transgene expression in keratinocytes suggested that high mobility group 1 protein increased transfer of the DNA from the cytoplasm to the nucleus. Direct injection of the DNA-high-mobility-group-1 complex is a highly efficient method for introducing genes into keratinocytes in connection with gene therapy.

Animals↗
PubMed1991

Local skin response in mice induced by a single intradermal injection of bacterial lipopolysaccharide and lipid A.

Dermal inflammation and hemorrhagic necrosis induced by bacterial lipopolysaccharide (LPS) and lipid A were studied in mice. In ddY mice, a single intradermal injection of Salmonella typhimurium S-form LPS and lipid A into the abdominal dermis elicited an edematous change due to an increase in local vascular permeability 12 h postinjection, followed by hemorrhagic necrosis from 24 to 72 h. This skin reaction was also induced in a dose-dependent manner by S-form LPS, R-mutant LPS, and lipid A of S. typhimurium and Escherichia coli, but not by polysaccharide from Salmonella S-form LPS. The dermal inflammation-inducing activities of LPS and lipid A were roughly in the following order (from highest to lowest): Re-form LPS, Rc-form LPS and lipid A, Ra-form LPS, and S-form LPS. These results suggest that the lipid A portion of the LPS molecule is responsible for the skin reaction. In C3H/HeN mice, Re-form LPS and lipid A induced the same intensity of skin reaction as that in ddY mice. In C3H/HeJ mice, which have a low response to LPS, Re-LPS and lipid A did not induce any hemorrhagic response but showed a distinct edematous change. Although hemorrhagic necrosis and edematous changes could be explained by quantitative differences in skin lesions, the other possible explanation is that hemorrhagic necrosis and the increase in local vascular permeability are induced by different mechanisms, only one of which depends on the regulation of the lps gene.

Animals↗
PubMed2003

The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of capsaicin.

This study was designed to assess the role of calcitonin gene-related peptide (CGRP) and its receptor in the generation and maintenance of secondary mechanical allodynia and hyperalgesia induced by intradermal injection of capsaicin in rats. Paw withdrawal responses (PWRs) to von Frey hairs with different bending forces applied on the rat paw were tested in this study. CGRP(8-37), a specific antagonist of CGRP 1 receptors, was delivered through a microdialysis fiber inserted across the dorsal horn. Post- and pretreatment paradigms were followed. When CGRP(8-37) was administered 1h after capsaicin injection, the mechanical allodynia and hyperalgesia were partially reversed in a dose-dependent manner. On the other hand, when rats were treated with CGRP(8-37) prior to capsaicin injection, the PWRs to von Frey applications were significantly reduced as compared to control animals. Collectively, these results suggest that CGRP receptors present in the dorsal horn are involved in the generation and maintenance of nociceptive behaviors associated with cutaneous inflammation.

Animals↗
PubMed1967

Comparative trial of live attenuated measles vaccine in Hong Kong by intramuscular and intradermal injection.

Between April and July 1966 a comparative trial of two live attenuated measles vaccines (Schwarz and Beckenham 31), given intramuscularly or intradermally, was conducted in Hong Kong. Some 910 non-immune children completed the trial. The Beckenham 31 vaccine caused significantly more complications than Schwarz vaccine, but it also resulted in a much higher mean antibody titre by both intramuscular and intradermal injection than did Schwarz vaccine. The seroconversion rates were satisfactory for both vaccines given intramuscularly but not for either given intradermally (at one-fifth the recognized intramuscular dose).The authors suggest that either vaccine may usefully be given for measles prophylaxis. The choice between Beckenham 31, with a higher complication rate and higher antibody levels, and Schwarz, with fewer complications but lower antibody levels, would depend on the type of community, the adequacy of the medical services, the severity of measles and an assessment of how either vaccine, with its known complications, might affect other immunization programmes.

Asian People↗
PubMed1994

Repeated intradermal injection of low-dose carrageenan induces tachyphylaxis to evoked hyperalgesia.

Changes in the thresholds to noxious mechanical and thermal stimulation were monitored in a group of normal sheep at different times (30 min-24 h) following intradermal injection of either low-dose (0.0625%) carrageenan, a widely used mucopolysaccharide irritant, or saline (0.9%) into the lateral aspect of the fore limb. Thresholds to noxious mechanical stimulation were measured on the ipsilateral limb whereas thresholds to noxious thermal stimulation were measured at a site distant to that of the injection, the ipsilateral ear. During the first 2 h after carrageenan injection the thresholds to noxious thermal stimulation fell, while thresholds to noxious mechanical stimulation were unaltered. The evoked hyperalgesia was reversed by the administration of non-steroidal anti-inflammatory agents. Hyperalgesia was not present 4 h after carrageenan injection in control or treated animals. This experiment was carried out on 3 further occasions and a diminishing response to injection of carrageenan was observed, suggesting development of tachyphylaxis to evoked thermal hyperalgesia.

Animals↗
PubMed1995

Effects of intradermal injection of atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) causes mast cell degranulation in rats in vivo and in vitro but is bronchodilator in humans. The aim of this study was to investigate the wheal and flare dose-response to intradermal injection of alpha-human ANP in normal humans. Eight normal subjects received five 30 microliters injections containing 1, 10, 39, 78, 117 pmol ANP and one each of normal saline, histamine 675 pmol and substance P 30 pmol. Maximum ANP flare response was greater but not significantly than that to saline at 1.55 +/- 0.6 (mean +/- s.e. mean) compared with 0.42 +/- 0.17 cm2, but much less than to histamine 9.86 +/- 0.97 or to substance P 12.5 +/- 1.2. Maximum ANP wheal response was significantly greater than that to saline at 0.38 +/- 0.08 compared with 0.18 +/- 0.05 cm2 (difference between means 0.20, 95% CI 0.05, 0.35), but much less than to histamine 0.75 +/- 0.06 or to substance P 1.05 +/- 0.08 cm2. No dose-response to ANP was demonstrated, though responses to the highest dose differed significantly from those to the lowest dose studied. We conclude that human cutaneous responses to ANP differ from those of animals and that the skin is less responsive than other tissues in humans.

Adult↗
PubMed2005

Protein phosphatase modulates the phosphorylation of spinal cord NMDA receptors in rats following intradermal injection of capsaicin.

The present study investigates the role of serine/threonine protein phosphatase 2A (PP2A) in the modulation of the phosphorylation of the NR1 and NR2B subunits of NMDA receptors in the spinal cord of rats following intradermal injection of capsaicin. The effects of a specific inhibitor of PP2A, fostriecin, on the expression of NR1, phospho-NR1, NR2B, and phospho-NR2B subunits of the NMDA receptor in the spinal cord of rats following noxious stimulation were examined. After continually perfusing with ACSF or fostriecin (3 microM) through a previously implanted microdialysis fiber for 30 min, central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw of rats. The spinal cord was removed at different time points (30, 60, 90, 120, 180 min) after intradermal injection of capsaicin. Western blots were performed to examine the expression of NMDA subunits in spinal cord tissue by using specific antibodies. We found that the upregulated phosphorylation of both NR1 and NR2B subunits induced by capsaicin injection was significantly potentiated by the PP2A inhibitor without affecting the NR1 and NR2B protein itself. These results suggest that PP2A may have a regulatory effect on central sensitization induced by noxious stimuli in the periphery by regulating the phosphorylation state of NMDA receptors.

Administration, Cutaneous↗
PubMed1990

Intradermal injections of bradykinin or histamine cause a flare-like vasodilatation in monkey. Evidence from laser Doppler studies.

The spreading cutaneous vasodilatation (flare) that follows a cutaneous injury is readily visible in humans but cannot be visualized in monkey. To determine if monkeys exhibit this neurally mediated reaction, cutaneous blood flow changes after intradermal injections of bradykinin and of histamine were monitored in the hairy skin of pentobarbital anesthetized monkeys. Using a laser Doppler device, recordings of cutaneous blood flow were made at distances of 15 and 25 mm from the injection of 50 microliters of saline, bradykinin (10(-3) M) and histamine (10(-3) M). These sites were beyond the radius of the wheal caused by bradykinin (6.3 mm) or histamine (6.8 mm). At both recording sites, both drugs caused an increase in blood flow that was significantly larger than that caused by the injection of the same volume of saline. These results provide evidence that although a flare is not visible in monkey skin, a flare-like vasodilatation does occur over an area of at least 50 mm diameter.

Animals↗
PubMed2004

Abnormal contralateral pain responses from an intradermal injection of phenylephrine in a subset of patients with complex regional pain syndrome (CRPS).

We have examined the effect of an intradermal injection of phenylephrine (1mg/0.1 ml), an alpha-1-adrenoceptor agonist in normal subjects, and patients with sympathetically-independent (SIP) and sympathetically-maintained pain (SMP). Normal subjects and SIP patients experienced only brief stinging pain, while subsets of both sympathectomized and non-sympathectomized SMP patients (6/9 and 4/8, respectively) experienced an additional abnormal pain response accompanied by mechano-allodynia around the injection site. Both the normal and abnormal pain response after intradermal phenylephrine are similar to those observed with intradermal norepinephrine. In contrast to previous reports in the literature, we found that three sympathectomized SMP patients (who, however, had failed to experience pain relief after surgical sympathectomy despite very good relief after sympathetic blocks) also experienced abnormal pain and mechano-allodynia when phenylephrine was injected to a limb contralateral to the symptomatic sympathectomized extremity. Abnormal pain response evoked by norepinephrine or phenylephrine injection in the ipsilateral symptomatic limb of SMP patients may be due to injury-evoked nociceptor responsiveness to catecholamines. However, such a response in contralateral asymptomatic limbs suggests an additional factor that more likely than not is of central origin and may or may not be related to sympathectomy and its success or failure to treat pain.

Complex Regional Pain Syndromes↗
PubMed2004

Sympathetic modulation of activity in Adelta- and C-primary nociceptive afferents after intradermal injection of capsaicin in rats.

Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of Adelta- and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some Adelta- and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 mul) injection, but the enhanced responses of both Adelta- and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an alpha(1)-adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of Adelta-fibers. In contrast, a blockade of alpha(2)-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of Adelta- and C-primary afferent fibers to mechanical stimuli and that alpha(1)-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.

Action Potentials↗
PubMed1979

Epidermal hyperplasia induced in guinea pig flank skin by intradermal injection of Sudan red.

Studies of dermal-epidermal interactions were conducted with guinea pig flank skin and intradermal injections of the irritant, Sudan IV dye in olive oil. These injections led to epidermal hyperplasia in areas overlying the irritant and the effect was most significant when the irritant was placed in the upper dermis. Basal cell mitotic activity and thymidine uptake reached a peak by 24 h and thereafter dropped rapidly. Maximal epidermal thickness (4.3 times the control) resulting from an increase in cell number occurred within 2-4 days. Despite the very short period of increased cell growth, epidermal thickness returned to control values only after a 24-day period. A similar growth response could not be induced by saline injections. A single topical application of the irritant showed a qualitatively and quantitatively different epidermal response. These experiments indicate that an intradermal irritant can lead to epidermal hyperplasia and a long-lasting epidermal thickening.

Animals↗
PubMed1999

A model for vaccinia virus pathogenesis and immunity based on intradermal injection of mouse ear pinnae.

Vaccinia virus (VV) proteins that interfere with the host response to infection are of interest because they provide insight into virus-host relationships and may affect the safety and immunogenicity of recombinant VV (rVV) vaccines. Such vaccines need assessment in animal models and with this aim a model of VV infection based on intradermal injection of BALB/c ear pinnae was developed and characterized. In this model, the outcome of infection is affected by the dose of virus inoculated but virus spread is minimal and the mice suffer no signs of systemic illness. Cellular and humoral immune responses to these infections were measured readily and were independent of virus dose over a 100-fold range. Thus the model seems suitable for the analysis of the safety and immunogenicity of VV mutants lacking specific immunomodulatory proteins or bearing foreign antigens.

Animals↗
PubMed2001

NMDA or non-NMDA receptor antagonists attenuate increased Fos expression in spinal dorsal horn GABAergic neurons after intradermal injection of capsaicin in rats.

GABAergic neurons play an important role in the generation of primary afferent depolarization, which results in presynaptic inhibition and, if large enough, triggers dorsal root reflexes. Recent electrophysiological studies by our group have suggested that increased excitation of spinal GABAergic neurons by activation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors following intradermal injection of capsaicin results in the generation of DRRs that contribute to neurogenic inflammation. The present study was to determine if changes in the expression of Fos protein occur in GABAergic neurons in the lumbosacral spinal cord following injection of capsaicin into the glabrous skin of one hind paw of anesthetized rats and if pretreatment with an NMDA receptor antagonist, D-(-)-2-amino-7-phosphonoheptanoic acid (AP7) or a non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocks Fos expression in these neurons. The experiments used western blots and immunofluorescence double labeling staining following capsaicin or vehicle injection. Western blots showed that Fos protein was increased on the ipsilateral side in spinal cord tissue 0.5 h after capsaicin injection. Pretreatment with AP7 or CNQX caused a decrease in capsaicin-induced Fos expression. Immunofluorescence double labeling showed that the proportion of Fos-positive GABAergic neuronal profiles was significantly increased following capsaicin injection (48.8+/-4.8%) compared to the vehicle injection (23.8+/-5.1%) in superficial laminae on the ipsilateral side in lumbosacral spinal cord (P<0.05). However, when the spinal cord was pretreated with AP7 (5 microg) or CNQX (0.2 microg), only 9.1+/-0.6% or 7.1+/-0.8% of GABA-immunoreactive neuronal profiles were stained for Fos following capsaicin injection. The blockade of the capsaicin-evoked Fos staining was dose-dependent. These findings suggest that GABAergic neurons take part in dorsal horn circuits that modulate nociceptive information and that the function of GABAergic neurons following capsaicin injection is partially mediated by NMDA and non-NMDA receptors.

2-Amino-5-phosphonovalerate↗