Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Injections, Intradermal”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources
PubMed1995

Cutaneous injection of the capsaicin analogue, NE-21610, produces analgesia to heat but not to mechanical stimuli in man.

Intradermal injection of the capsaicin analogue, NE-21610 (Procter and Gamble), inactivates nociceptors but not low-threshold mechanoreceptors in monkey. The present study examined the effects of cutaneous NE-21610 on heat and mechanical sensation in normal human volunteers. In the first series of experiments, subjects received intradermal (i.d.) injections (30 microliters) of the vehicle alone or with the drug (0.3, 3.0, 10 micrograms) into different sites on the volar forearm. Subjects were randomly assigned to 1 of 3 protocols to examine drug-evoked pain (n = 8), or alterations in pain to heat (n = 8) or mechanical (n = 8) stimuli induced by the drug. An additional 7 subjects rated pain to mechanical and heat stimuli before and after subcutaneous (s.c.) injections (300 microliters) of the vehicle or drug (100 micrograms). The peak pain occurred at the time of injection, was of short duration, and was similar for vehicle and drug injections. A mild, dose-related pain followed that lasted up to 2 h. Von Frey thresholds for detection, sharpness, and pain at the injection site (measured 24 h after injection) were not significantly altered by either i.d. or s.c. drug administration. However, pain to stepped heat stimuli was reduced in a dose-dependent fashion for both types of injection. At the highest drug doses, analgesia to heat stimuli was still present 1 week after injection. Recovery of heat sensitivity occurred several weeks after injection. This dissociated loss of heat but not mechanical pain sensibility may be due to: (1) a selective action of the drug on heat transducers in nociceptors responsive to both heat and mechanical stimuli, or (2) a selective action on that subset of nociceptors responsible for signaling heat-evoked pain.

Analgesia↗
PubMed1982

Role for endotoxin in the leukocyte infiltration accompanying Escherichia coli inflammation.

Escherichia coli organisms induce polymorphonuclear leukocyte (PMNL) infiltration during clinical infection and also in a rabbit dermal model of inflammation. We investigated the factors which may mediate this host response to E. coli. In vitro incubation of Formalin-killed E. coli in heat-inactivated rabbit plasma or balanced salt solution generated in the supernatant factors which induced in vivo PMNL infiltration upon intradermal injection into rabbits. However, these supernatants, in the presence or absence of plasma, did not induce PMNL migration in vitro. The in vivo activity was stable at 100 degrees C and of high molecular weight (30,000). Antiserum to O antigen or to core glycolipid, but not to K or H antigen, as well as polymyxin B inhibited the release or activity of these E. coli-derived factors. The intradermal injection of 0.02 to 0.2 mug of four different endotoxin preparations or lipid A also induced marked PMNL infiltration in vivo. However, these preparations did not stimulate PMNL migration in vitro and failed to generate chemotactic activity in plasma except at very high concentrations (500 mug/ml). Anti-O serum inhibited PMNL infiltration induced by endotoxins with the corresponding O antigen and anti-core glycolipid serum inhibited all four endotoxins tested, whereas polymyxin B inhibited the activity of the endotoxins as well as that of lipid A. Base hydrolysis of endotoxin abolished PMNL infiltration. It is concluded that (i) endotoxin shed from E. coli (killed or live) may be one factor mediating the PMNL infiltration induced by this organism, (ii) endotoxin probably acts independent of in vivo complement activation, (iii) the activity is dependent on the lipid A moiety, and (iv) antibody binding to O or core glycolipid antigens can modify endotoxin so as to diminish its capacity to induce PMNL infiltration in vivo.

Animals↗
PubMed1988

Evidence that neutrophil accumulation induced by interleukin-1 requires both local protein biosynthesis and neutrophil CD18 antigen expression in vivo.

1. Mechanisms involved in neutrophil accumulation induced by intradermal injection of interleukin-1 (IL-1) in the rabbit were investigated using intravenously-injected 111In-labelled neutrophils. C5a des Arg, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4) were included for comparison. 2. Local inhibition of protein biosynthesis in the skin using actinomycin-D or cycloheximide blocked 111In-neutrophil accumulation induced by IL-1, but not that induced by the other mediators. 3. Actinomycin-D and cycloheximide had no effect on local plasma protein leakage induced by intradermally-injected C5a des Arg, or that induced by zymosan. 111In-neutrophil accumulation induced by zymosan was, however, partially suppressed. 4. A monoclonal antibody, MoAb 60.3, recognising neutrophil surface CD18 antigen, was preincubated with 111In-neutrophils before intravenous injection. This pretreatment did not affect circulating numbers of radiolabelled cells, but it inhibited their accumulation in response to IL-1, C5a des Arg and the other mediators. 5. The results suggest that neutrophil accumulation induced by IL-1, but not the other mediators, requires local protein biosynthesis, probably in the microvascular endothelium. Neutrophil accumulation to IL-1 and the other mediators appears to require neutrophil surface antigen, CD18. The inflammatory response to zymosan may be mediated by both endogenous C5a des Arg and IL-1.

Animals↗
PubMed2001

Lymphoscintigraphy and sentinel node localization in breast cancer patients: a comparison between 1-day and 2-day protocols.

UNLABELLED: The purpose of this study was to compare the results of isotope injection the morning of surgery (1-d protocol) with isotope injection the day before surgery (2-d protocol) in patients having sentinel lymph node (SLN) biopsy for breast cancer. METHODS: The 1-d (protocol 1) and 2-d (protocol 2) protocols included 514 and 152 patients, respectively, treated contemporaneously by surgeons experienced with the SLN biopsy technique. All had preoperative lymphoscintigraphy (LSG) and SLN biopsy using both blue dye and (99m)Tc-sulfur colloid. All patients had a single-site intradermal injection of unfiltered (99m)Tc-sulfur colloid in 0.05 mL normal saline: 3.7 MBq (0.1 mCi) on the morning of surgery for protocol 1 and 18.5 MBq (0.5 mCi) on the afternoon before surgery for protocol 2. RESULTS: The patients in protocols 1 and 2 were comparable in terms of age, tumor size, tumor location, histologic type, node positivity, and frequency of a previous surgical biopsy. Comparing protocols 1 and 2, early (30 min) LSG images found the SLN equally often (69% vs. 68%). Isotope identified the SLN equally often at surgery (93% vs. 97%) as did isotope plus dye (98% vs. 99%). A comparable number of SLNs was found (2.5 vs. 2.8 per axilla), and the concordance between isotope and dye in the SLN was also comparable (97% vs. 95%). Late LSG images (at 2 h, possible only for protocol 2) identified the SLN in significantly more patients compared with early images (86% vs. 68%). CONCLUSION: With unfiltered (99m)Tc-sulfur colloid injected intradermally, the results of SLN biopsy under the 1-d and 2-d protocols are virtually identical. A 2-d protocol allows increased efficiency in scheduling, both for nuclear medicine physicians and for the operating room, with no compromise in the effectiveness of SLN mapping.

Adult↗
PubMed1998

Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice.

Our experiments were conducted to determine whether substance P (SP) would elicit an itch sensation mediated by mast cells in mice. An intradermal injection of SP (10-135 microgram site-1) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site. The SP- (135 microgram site-1 = 100 nmol site-1) induced scratching was inhibited by capsaicin (repeated administration) and naloxone; features being similar to itch in humans. SP elicited scratching in mast cell-deficient (WBB6F1 W/Wv) mice as well as control (+/+) mice. Pretreatment with compound 48/80 produced similar degrees of inhibition of SP-induced scratching in mast cell-deficient mice as well as control +/+ and ICR mice. Intradermal injections of the NK1 receptor agonist GR73632 produced dose-dependent scratching, while the NK2 agonist GR64349 and the NK3 agonist senktide were without effects. SP-induced scratching was inhibited by the NK1 receptor antagonists spantide and L-668,169, but not by the NK2 antagonist L-659,877. The results suggest that scratching of the mouse induced by an i.d. injection of SP is itch-associated response. The SP action may be mediated at least partly by cutaneous NK1 receptors, and mast cells may not be key factors in SP-induced itching.

Animals↗
PubMed1984

Defective beta adrenergic response of cystic fibrosis sweat glands in vivo and in vitro.

Abnormal ductal NaCl absorption has been known as the only defect in cystic fibrosis (CF) sweat glands. We have fortuitously found that the secretory portion of CF sweat glands is also abnormal in that it failed to show a sweating response to beta adrenergic stimulation (isoproterenol, [ISO]) both in vivo and in vitro. For the in vitro sweat test, eccrine sweat glands were isolated from skin biopsy specimens of the forearm, cannulated, and stimulated to secrete sweat. All 14 isolated CF sweat glands failed to respond to ISO + theophylline (TH, as aminophylline), but 17 of 18 control glands responded with a mean rate (SR) of 1.1 nl/min per gland. Cholinergic responsiveness of isolated CF sweat glands was comparable with that of control glands. The in vivo sweat test was performed by intradermal injection in the forearm of 0.2 ml of 2.4 or 8 X 10(-5) M ISO with or without 10(-2) M TH (and 1.4 X 10(-4) M atropine as a necessary anticholinergic agent). The beads of sweat secreted into the oil-filled sweat collection ring glued to the skin were then collected with a glass capillary under a stereomicroscope. Of 28 CF patients, 26 failed to show a secretory response to intradermal injection of ISO + TH, and 2 CF patients gave SR of less than 0.007 nl/min per gland in the first test but no response in the repeat test performed later. In contrast, all 35 age- and sex-matched control subjects responded with the mean SR of 0.72 nl/min per gland. Response of CF patients to epinephrine and phenylephrine was comparable with control, indicating that the alpha adrenergic responsiveness of CF sweat glands is not defective. A preliminary attempt was made to determine tissue cyclic AMP accumulation by radioimmunoassay in isolated sweat glands. No significant difference was observed between CF and control glands in their maximal accumulation of tissue cAMP in response to ISO or ISO + TH, except that the rise time of ISO + TH-induced cAMP accumulation in CF glands was significantly slower during the first 5 min of incubation. The data suggest that beta adrenergic regulation is abnormal in CF sweat glands and justifies further investigations into the mechanism of beta adrenergic regulation of the eccrine sweat gland in both normal and CF subjects.

Atropine↗
PubMed1996

Biphasic changes in behavioral, endocrine, and sympathetic systems in adjuvant arthritis in Lewis rats.

Adjuvant arthritis (AA) is an experimental model for rheumatoid arthritis, and is induced most easily in inbred Lewis rats by an intradermal injection of heat-killed Mycobacterium tuberculosis (MT) in incomplete Freund's adjuvant. Susceptivity to the arthritis in Lewis rats is thought to be related to a defect in their responses of the hypothalamo-pituitary-adrenal (HPA) axis to the disease. Because the use of an inbred strain is necessary for our immunological studies, we examined in Lewis rats changes in behavior, the HPA axis, and sympathetic nerve activities during development of the adjuvant arthritis. Following intradermal injections of heat-killed MT in adjuvant, the arthritis began to develop on day 12, reaching its maximum severity on day 21, and remained at the level for over a month. The body temperature rose from day 0 to 5 (the primary phase--before the onset of the arthritis). It then fell to normal temperature, and again rose from day 10 to 21 (the secondary phase--with fully developed arthritis). The behavioral (physical activity, food, and water intake) and hormonal parameters [plasma adrenocorticotropic hormone (ACTH) and corticosterone levels] also changed in two phases, similar to those observed in the temperature responses. No change in plasma vasopressin level was observed. Sympathetic nerve activities, assessed by changes in plasma noradrenalin levels, increased more in the primary than in the secondary phase. The possible causes for the biphasic changes associated with development of arthritis are discussed.

Animals↗
PubMed1975

[Use of an immunologic test for differential diagnosis of uterine chorionepithelioma and hydatid mole].

Polysaccharide complexes obtained by Westphal's method (modified by L. A. Zilbert et al) from the tissue of a primary tumour node and remote metastases (the lungs) of chorionoepithelioma of the uterus were used for differential diagnosis of chorionepithelioma of the uterus and hydatid mole. Investigations carried out showed that the reaction to the intradermal injection of polysaccharide complexes obtained from the remote metastases (the lungs) of chorionepithelioma of the uterus was highly specific and sensitive: positive reaction occurred only in the patients with chorionepithelioma of the uterus, and it was negative in the patients with hydatid mole. With a marked diminution (in the course of chemotherapy) of metastases in the lungs, when the immunological reaction to chorionic gonadotropin fell to 300--100 IU per litre of the urine, reaction to the intradermal injection of polysaccharide complexes from the metastases of chorionepithelioma of the uterus still remained positive.

Antigens, Neoplasm↗
PubMed1987

Vascular permeability induced by protein product of malignant brain tumors: inhibition by dexamethasone.

Serum-free conditioned medium derived from confluent monolayer cultures of malignant human astroglial tumors contains a substance that rapidly increases capillary vascular permeability after intradermal injection into guinea pigs. Accumulation of vascular permeability factor (VPF) activity occurs with increasing duration of tumor incubation in vitro. Expression of this activity is inhibited by incubation of cell cultures with cycloheximide or dexamethasone. This VPF is an acid-stable heat-labile macromolecule that is inactivated by trypsin and pepsin and binds immobilized heparin. Activity is retained by ultrafiltration with 30,000-dalton cut-off microconcentrators. Pretreatment of test animals with systemic dexamethasone prior to intradermal injection of VPF diminishes microvascular permeability. Furthermore, VPF activity is not inhibited by antihistamines. Secretion of VPF may cause the vasogenic brain edema that is frequently associated with malignant primary and metastatic intracerebral tumors. Inhibition by dexamethasone of both VPF expression in tissue culture, and VPF activity at the microvascular level in test animals, is in keeping with the known efficacy of this agent in treating the vasogenic edema associated with brain tumors.

Animals↗
PubMed1994

Leukocyte recruitment into human skin transplanted onto severe combined immunodeficient mice induced by TNF-alpha is dependent on E-selectin.

In order to study the in vivo role of E-selectin in human inflammation, we have developed a model in which human skin is transplanted onto severe combined immunodeficient (SCID) mice. The grafted skin closely resembles normal skin and retains its human vasculature. After intradermal injection of rTNF-alpha, human E-selectin was rapidly up-regulated on dermal microvessels, with significant expression (determined immunohistochemically) at 1 h postinjection and maximum expression at 2 h postinjection. To study the functional role of E-selectin, a murine Ab against human E-selectin (mAb HEL 3/2) was developed that inhibited the in vitro adhesion of both human U937 cells and murine 32D cells to TNF-alpha-stimulated human endothelial cells. After intradermal injection of TNF-alpha, large numbers of murine leukocytes migrated into the grafts within 2 h. Intravenous injection of the antihuman E-selectin mAb 3/2 completely inhibited murine white blood cell (WBC) transmigration into the skin grafts, but an isotype-matched control Ab that also bound to human endothelium had no effect. Antihuman E-selectin mAb 3/2 was also able to inhibit the migration of i.v. 51Cr-labeled human neutrophils. These findings demonstrate that E-selectin is important in early white blood cell adhesion events and is required for TNF-alpha-induced white blood cell transmigration in the human/SCID mouse chimeric model.

Animals↗
PubMed1993

Chemosensitivity and sensitization of nociceptive afferents that innervate the hairy skin of monkey.

1. A large proportion of the cutaneous nociceptor population in monkey either does not respond to mechanical stimuli or has very high mechanical thresholds (> 6 bar). The goal of this study was to determine whether these mechanically insensitive nociceptive afferents (MIAs) differ from mechanically sensitive nociceptive afferents (MSAs) with regard to responses to chemical stimuli. 2. Teased-fiber techniques were used to record from 28 A delta-fiber (16 MIAs and 12 MSAs) and 23 C-fiber (10 MIAs and 13 MSAs) nociceptors in hairy skin of pentobarbital sodium-anesthetized monkeys. An electrocutaneous search technique was used to locate the putative receptive fields of the MIAs. The response to mechanical and heat stimuli was determined before and after intradermal injection of a standard mixture of algesic/inflammatory mediators (bradykinin, histamine, serotonin, and prostaglandin E1). 3. All 25 MSAs, but only 65% of the MIAs, responded to the chemical stimulus. The A delta-fibers, both MSAs and responsive MIAs, and the responsive C-fiber MIAs gave a robust discharge. In contrast, the C-fiber MSAs (the conventional polymodal C-fiber nociceptors) exhibited a significantly weaker response. Three MIAs responded only to the chemical mixture and not to mechanical or heat stimuli. 4. Before injection of the chemical mixture, a significantly smaller proportion of C-fiber MIAs (50%) than of C-fiber MSAs (92%) responded to heat stimuli, whereas a similar proportion (38%) of A delta-fiber MIAs and MSAs were heat sensitive. 5. Approximately one-half of the MIAs and MSAs were sensitized to mechanical stimuli after the chemical injection, as manifest by a decreased threshold and/or an enlarged receptive field. 6. The chemical injection sensitized 90% of A delta-fiber MSAs, but only 8% of A delta-fiber MIAs, to heat stimuli. In contrast, 38% of C-fibers were sensitized. 7. In 14 fibers, the chemical stimulus resulted in sensitization to mechanical stimuli without sensitization to heat stimuli, or vice versa. This dissociated sensitized state suggests that the molecular mechanisms of sensitization to heat and mechanical stimuli differ. 8. In conclusion, a large proportion of primate cutaneous nociceptors respond to intradermal injection of algesic/inflammatory mediators and may also become sensitized to mechanical and/or heat stimuli.

Animals↗
PubMed1986

Doxorubicin-induced skin necrosis in the swine model: protection with a novel radical dimer.

The treatment of doxorubicin (DOX) extravasation tissue injury is poorly defined. A swine model has been developed to study DOX skin toxicity and potential pharmacologic antidotes. Intradermal injections of DOX in miniature female weanling swine produced predictable and dose-dependent ulcerations that closely resemble lesions observed in humans following extravasation of DOX. The ulcers reached maximal size at 3 weeks following DOX administration and were completely healed by 7 weeks. Bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3) is a radical dimer that can react with DOX in vitro to produce deoxydoxorubicin aglycone, an inactive anthracycline metabolite. When DHM3 was administered into the same intradermal injection site 15 minutes after DOX, the maximum ulcer size was reduced 80%, and the healing time was reduced to 5 weeks. The protection from toxicity was highly dependent on the time interval between DOX and DHM3 injections, with no protection noted after a 60-minute interval. Our data verify the swine model as a useful tool to study DOX-induced extravasation injury. Furthermore, DHM3 is an effective antidote for DOX-induced skin necrosis and has potential for clinical use.

Animals↗
PubMed1990

Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs.

Skin mast cells release the neutral protease chymase along with histamine during degranulation. To test the hypothesis that chymase modulates histamine-induced plasma extravasation, we measured wheal formation following intradermal injection of purified mast cell chymase and histamine into the skin of ragweed-allergic dogs. We found that chymase greatly augments histamine-induced wheal formation. The magnitude of the potentiating effect increases with increasing doses of chymase and becomes maximal approximately 30 min after administration. Injection of chymase without histamine does not evoke wheal formation. The chymase potentiation of histamine-induced skin responses is prevented completely by pretreatment with the H1-receptor antagonist pyrilamine, and is prevented by inactivation of chymase with soybean trypsin inhibitor, suggesting that both histamine and preserved catalytic activity are required for the effects of chymase. To examine the effects of histamine and chymase released in situ in further experiments, we measured wheal size following local degranulation of mast cells by intradermal injection of ragweed antigen or compound 48/80. We found that pretreatment with either soybean trypsin inhibitor or pyrilamine markedly reduces ragweed antigen- or 48/80-induced wheal formation, supporting the results obtained by injection of exogenous chymase and histamine. These findings suggest a novel and important proinflammatory role for chymase in modulating the effects of histamine on vascular permeability during mast cell activation.

Allergens↗
PubMed1996

A sequential study of the bovine tuberculin reaction.

The sequential histopathological and immunocytochemical changes that characterize the tuberculin reaction were studied in 13 cattle experimentally sensitized to Mycobacterium bovis, and 14 cattle naturally infected with M. bovis. There were two distinct, temporally related patterns of morphological change that were similar for both groups of cattle. The first phase, between 6 hr and 24 hr after the intradermal injection of purified protein derivative (PPD), was characterized by a perivascular aggregation of WC1+ gamma delta T cells and neutrophils and the presence of leucocytoclastic vasculitis within the papillary dermis. The second phase of the reaction was characterized by increased numbers of infiltrating BoCD4+ cells, BoCD8+ cells and macrophages, as well as an increase in expression of the interleukin-2 (IL-2) receptor and the ACT2 antigen. Macrophages were the most numerous infiltrating leucocytes between 24 hr and 72 hr after the intradermal injection of PPD. At 72 hr, the reaction was characterized by intense perivascular cuffing with BoCD4+ cells, BoCD8+ cells and macrophages; gamma delta T cells and neutrophils were a minor component of the reaction and leucocytoclastic vasculitis was no longer observed. No B cells were detected in the dermis throughout the period of study. The increase in skin thickness was primarily because of inflammatory oedema that was contained within the area by a meshwork of fibrin deposited around the collagen bundles of the reticular dermis.

Animals↗
PubMed1998

Antitumor effect of a peptide-glucan preparation extracted from Agaricus blazei in a double-grafted tumor system in mice.

The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill was examined in a double-grafted tumor system, in which BALB/c mice received simultaneous intradermal injections of Meth-A tumor cells in both the right (10(6) cells) and left flank (2 x 10(5) cells), and were then injected with 5 mg of extracts of A. blazei in the right tumor on days 3, 4 and 5. Intratumoral administration of ethanol-soluble (Fraction 1), water-ethanol-soluble (Fraction 2), ammonium oxalate-soluble (Fraction 3) and ammonium oxalate-insoluble (Fraction 4) fractions resulted in inhibition of tumor growth, with Fraction 3 showing the most tumoricidal activity, producing regression of the right tumor and inhibition of growth of the left, non-injected tumor. The maximum effect was obtained using 0.5 mg of Fraction 3 and this amount was used in subsequent experiments. The antitumor effect of intratumorally administered Fraction 3 was enhanced by oral ad lib administration of feed containing 0.083% of Fraction 3. When immunized spleen cells from mice that had been cured by intratumoral administration of 0.5 mg of Fraction 3 were directly injected (2 x 10(7) cells/mouse) into the Meth-A tumor, tumor growth was inhibited. The tumor cells on day 7 from the Fraction 3-treated right tumor and from the left tumor were cultured for 24 h and their culture supernatants were assayed for neutrophil or macrophage chemotactic activity. Significant macrophage chemotactic factor activity was detected in the culture media from the left tumor tissue. Serum levels of immunosuppressive acidic protein (IAP), produced by activated macrophages and neutrophils, increased transiently soon after intradermal injection of 0.5 mg of Fraction 3. These results suggest that regression of the left non-injected tumor was due to an immune reaction, involving induction of cytotoxic cells in the spleen, and the release of chemotactic factors in the distant tumor.

Adoptive Transfer↗
PubMed1997

Quantitative measurement of extracellular histamine concentrations in intact human skin in vivo by the microdialysis technique: methodological aspects.

Calculation of recovery is needed in microdialysis studied to calculate absolute concentrations of compounds in the extracellular water space. The purposes of this study were to determine the extracellular concentration of histamine in intact human skin in vivo and to study the validity of absolute histamine measurements during allergic skin reactions. A skin microdialysis technique and two calibration techniques, the no net flux method and the flow rate method, were used to quantify histamine concentrations in resting skin. To validate these techniques, skin glucose concentrations were analysed as well. In addition, the influence of vasodilation and plasma extravasation on recovery was followed after intradermal injection of codeine, a mast-cell secretagogue. As expected, both calibration methods estimated skin glucose concentrations to be identical with venous blood glucose concentrations. However, skin histamine levels could not be calculated by the no net method, because the data did not meet the theoretic assumptions of this method. In contrast, histamine data fitted theoretically with the flow rate method, and skin histamine concentrations of 18.8 +/- 2.8 nM were found to be significantly greater than plasma histamine concentrations of 4.3 +/- 0.7 nM. Within minutes after intradermal injection of codeine, recovery increased significantly in a dose-dependent fashion. Vasodilation per se did not influence recovery. In conclusion, absolute assessment of skin histamine concentrations can be made by microdialysis by the flow rate method. The validity of such an estimate and the theoretic prerequisites for the calculations are discussed. Quantitative measurement of skin histamine levels during allergic reactions cannot be performed since recovery is altered by plasma extravasation after skin challenge.

Adult↗
PubMed1994

Protein kinase C inhibitors decrease hyperalgesia and C-fiber hyperexcitability in the streptozotocin-diabetic rat.

1. We have previously demonstrated that although rats with streptozotocin-induced diabetes (STZ-D) have decreased behavioral mechanical nociceptive thresholds (hyperalgesia), their C-fiber primary afferent mechanical (von Frey hair) thresholds are not altered. Instead, when stimulated with a standardized sustained suprathreshold mechanical stimulus, C-fibers from STZ-D rats were found to have an increased number of spikes (hyperexcitability). We suggested that this C-fiber hyperexcitability contributes to the behavioral hyperalgesia and that agents that reverse the hyperalgesia may act by decreasing this hyperexcitability. Because protein kinase C activity contributes to C-fiber afferent excitability, we examined the effect of agents that inhibit protein kinases on behavioral mechanical nociceptive thresholds and on the response of C-fiber afferents to sustained mechanical stimulation. 2. The effects of intradermal injection of two protein kinase inhibitors, staurosporine and protein kinase C pseudosubstrate inhibitor peptide [PKC(19-36)], on behavioral mechanical nociceptive thresholds were determined using the Randall-Selitto paw-withdrawal device. These agents increased the mechanical nociceptive threshold of STZ-D rats in a dose-dependent manner but did not alter nociceptive threshold in control rats. 3. The same agents were tested for their effects on single C-fiber mechanical thresholds and excitability in response to suprathreshold (445 g) mechanical stimulation. Intradermal injection of staurosporine or PKC(19-36) significantly reduced the response of C-fibers from STZ-D rats to sustained suprathreshold mechanical stimulation but did not alter the response of C-fibers from control rats to the same stimulation. Neither agent altered mechanical threshold in C-fibers from either STZ-D or control rats. 4. In this study we found that both the mechanical behavioral hyperalgesia and the C-fiber hyperexcitability to mechanical stimuli seen in STZ-D rats are reduced by agents that inhibit protein kinase C. This evidence supports our hypothesis that C-fiber hyperexcitability, in part mediated by PKC activity, contributes to hyperalgesia in this model of diabetic neuropathy.

Alkaloids↗
PubMed1996

Sensitization of C-fibres by prostaglandin E2 in the rat is inhibited by guanosine 5'-O-(2-thiodiphosphate), 2',5'-dideoxyadenosine and Walsh inhibitor peptide.

Behavioral studies have shown that mechanical hyperalgesia induced by intradermal injection of prostaglandin E2 is blocked by inhibitors of the cAMP second messenger system. Similarly, injection of prostaglandin E2 also induces a decrease in mechanical threshold and an increase in the number of action potentials elicited by test stimuli in most C-fibre nociceptors. This change is called sensitization. To further evaluate the degree of correlation between primary afferent sensitization and mechanical hyperalgesia, we conducted a study to evaluate the effect of agents known to block the cAMP second messenger system and behavioral manifestations of mechanical hyperalgesia following injection of prostaglandin E2. The agents tested were guanosine 5'-O-(2-thiodiphosphate), an inhibitor of stimulatory guanine nucleotide-binding regulatory proteins; 2',5'-dideoxyadenosine, an inhibitor of adenylyl cyclase; and Walsh Inhibitor Peptide, an inhibitor of cAMP-dependent protein kinase. Single fibre electrophysiologic studies of 138 C-fibres, innervating the dorsum of the hind paw, was done in male Sprague-Dawley rats. The number of spikes evoked by a 10 s application of a threshold von Frey hair were determined before and after intradermal injection of test agents administered alone and in combination with prostaglandin E2. Injection of prostaglandin E2 with the test agent vehicle (saline or distilled water) resulted in a significant decrease in von Frey hair threshold and an increase in the number of spikes generated in response to threshold von Frey hairs. In contrast, co-injection of prostaglandin E2 with guanosine-5'-O-(2-thiodiphosphate), 2',5'-dideoxyadenosine or Walsh inhibitor peptide did not result in a significant decrease in von Frey hair mechanical threshold or increase in the number of spikes generated to the threshold stimuli, compared with vehicle/prostaglandin E2. It is suggested that guanosine 5'-O-(2-thiodiphosphate), 2',5'-dideoxyadenosine and Walsh inhibitor protein inhibited prostaglandin E2 sensitization of primary afferent C-fibres by inhibiting a stimulatory guanine nucleotide-binding regulatory protein, adenylyl cyclase, and protein kinase A, respectively. These results support the hypothesis that primary afferent sensitization by prostaglandin E2 underlies prostaglandin E2-induced hyperalgesia.

Animals↗