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PubMed1985

The effect of adjuvants and prior immunization on the rate and mode of uptake of antigen into afferent popliteal lymph from sheep.

Experiments were carried out to determine the effect of a range of adjuvants on the antibody response of sheep to a subcutaneous injection of ovalbumin. Incomplete Freund's adjuvant (IFA) was the best of the repository type adjuvants. From a range of soluble immunopotentiating substances tested, the polyion DEAE-dextran, or dextran sulphate, produced the greatest enhancement of the response. These results were confirmed in a factorial experiment, but no interactions were found between various classes of adjuvants. Further experiments were carried out to determine the effect of superior adjuvants, prior immunization or intradermal injection on the rate and mode of uptake of antigen from the injection site to afferent lymph. These experiments showed that, with IFA, most antigen is retained at the injection site, less than 15% entering lymph by 3 days. There was some delay in antigen uptake with adjuvant 65, while for aluminium phosphate precipitated antigen, the rate of uptake was the same as following a saline injection. There was some delay in uptake of antigen following injection with DEAE-dextran or in primed sheep but, following intradermal injection, the rate of uptake into lymph was the same as aqueous antigen injected subcutaneously. Experiments in which the distribution of radioactive antigen between cells and plasma in lymph was examined showed that, in unprimed sheep, virtually all antigen is unassociated with cells. In primed sheep, however, about 0.5% of antigen in lymph was found to be cell-associated. Gel filtration of lymph plasma from primed sheep demonstrated that nearly all the antigen in lymph is carried to the node as high molecular weight material, presumably antigen-antibody complexes.

Adjuvants, Immunologic↗
PubMed2003

Inflammatogenic properties of bacterial DNA following cutaneous exposure.

Bacterial DNA and oligodeoxynucleotides containing cytosine-phosphate-guanosine sequences and thereby mimicking prokaryotic DNA, have recently been shown to exert potent immunostimulatory properties. As skin normally harbors bacteria, and as the bacterial content and the levels of bacterial degradation products increase during skin infection, we analyzed the potential inflammatogenic role of bacterial DNA and oligodeoxynucleotides in a mouse model of cutaneous inflammation. Bacterial DNA from Staphylococcus aureus was injected intradermally into mice and its inflammatogenic properties were compared with synthetic phosphodiester and phosphorothioate cytosine-phosphate-guanosine- or GpC-containing oligodeoxynucleotides. A peak inflammatory infiltrate in the skin was seen already 2 d after injection with either bacterial DNA or the phosphodiester cytosine-phosphate-guanosine-oligodeoxynucleotides. In contrast, nuclease-resistant phosphorothioate cytosine-phosphate-guanosine-induced dermatitis peaked 7 d after intradermal injection. The inflammatory infiltrates consisted mainly of macrophages, and depletion of this cell population resulted in a significant (p=0.0001) decrease in the severity of inflammation, which suggests that macrophages play a central part in inflammatory responses in the skin following exposure to cytosine-phosphate-guanosine-containing oligodeoxynucleotides. A significant decrease in local inflammatory infiltrate was also seen in mice with deficiencies in neutrophil or lymphocyte populations, which indicates that these cell populations may also be involved in mediating inflammatory signals after the injection of immunostimulatory DNA sequences. In summary, our results suggest that bacterial DNA is an important virulence determinant and inflammatory stimulus during skin infections.

Administration, Topical↗
PubMed1990

Skin responses to intradermal histamine and leukotrienes C4, D4, and E4 in patients with chronic idiopathic urticaria and in normal subjects.

Mast cell inflammatory mediators, such as histamine, and newly formed compounds, such as the leukotrienes, cause wheal and flare when they are injected intradermally into normal subjects and may therefore play a role in the formation of urticaria. The effects of intradermal injections (50 microliters) of six different concentrations of histamine (range, 3.3 x 10(-4) to 3.3 x 10(-9) mol/L) and the leukotrienes C4, D4, and E4 (range, 2 x 10(-4) to 2 x 10(-9) mol/L) have been compared in 10 normal subjects and in 10 patients with chronic idiopathic urticaria. Wheal-and-flare sizes were measured at timed intervals up to 4 hours, and area under the curve for each response over time was calculated. There were no significant differences in leukotriene-induced responses between groups. Maximum sizes of histamine-induced wheal and flare were similar in each group of subjects. There were, however, significant increases in mean areas under the response curve of histamine wheal and flare in the patients with urticaria (wheal, p less than 0.001; flare, p less than 0.001; analysis of variance). These findings demonstrate a prolongation of skin responses to histamine in patients with urticaria and suggest an impaired clearance of histamine (or other vasoactive agents released by histamine) from the skin of these patients.

Analysis of Variance↗
PubMed2001

Modulation of gene-gun-mediated Th2 immunity to hepatitis B surface antigen by bacterial CpG motifs or IL-12.

Using different DNA vaccination techniques, we studied the IgG1/IgG2a antibody and MHC-I-restricted cytotoxic T lymphocyte (CTL) responses to the hepatitis B surface antigen (HBsAg) in mice. A single intramuscular injection of 100 microg HBsAg-encoding pCI/S plasmid DNA efficiently primed IgG2a antibody (IgG1/IgG2a ratio <0.3) and CTL responses to HBsAg (Th1 immunity). In contrast, a single intradermal injection of 1 microg of particle-coated pCI/S DNA with the gene-gun-primed IgG1 antibody responses to HBsAg (IgG1/IgG2a ratio >80) but there was no CTL response (Th2 immunity). Injection of immune-stimulating CpG-containing oligodeoxy-nucleotides (ODN) into the skin area used for gene-gun-mediated pCI/S DNA delivery shifted the polarization of the response towards Th1 immunity. A similar shift from Th2 to Th1 immunity was observed when the skin area used for gene-gun-mediated DNA transfer was conditioned by injection of recombinant IL-12. DNA vaccination can thus prime polarized immunity to HBsAg. The polarization of immunity is determined by the technique of plasmid DNA delivery as well as by conditions of the tissue into which DNA is inoculated. Th1 immunity to HBsAg (primed by injection of naked pCI/S DNA) dominated Th2 immunity (primed by gene-gun-mediated pCI/S DNA). In contrast, an established HBsAg-specific Th2 immunity was readily shifted towards Th1 immunity (including specific CTL priming) by an intramuscular boost injection of pCI/S DNA. These data contribute to the rational design of DNA vaccination strategies to efficiently prime anti-viral Th1 immune effector specificities using the gene gun.

Animals↗
PubMed1987

Hemolytic streptococcus preparation OK-432; beneficial adjuvant therapy in recurrent gastric carcinoma.

The administration of a hemolytic streptococcus preparation, OK-432, is thought to be of therapeutic value in the treatment of cancer patients through a stimulatory effect on the immune system. In order to evaluate any beneficial effect of such an administration, a group of patients with recurrent gastric cancer was studied. This group was randomly subdivided into 3 groups: 1) Intradermal group (ID Group), 42 patients given an intradermal injections of OK-432. 2) Intramuscular group (IM Group), 40 patients given an intramuscular injections of OK-432. 3) Control group (C Group), 39 patients not given injections. Each group was studied in regards to the length of survival, the host immune response and the incidence of side effects. When compared to the IM and C Groups, the ID Group showed improved survival. Accompanying this improved survival, the ID Group also had greater white cell and lymphocyte counts, a greater number of T cells, and a more dramatic skin reaction to the extracted cell wall polysaccharide of hemolytic streptococcus Su-strain (Su-PS). The ID Group, following OK-432 injection, had a 4.8% incidence of fever and a 52.4% incidence of local abscess formation at the injection site. 90% of the IM Group developed fever but abscess formation was absent in all patients. From these results, it was concluded that in the patients tested, intradermal injection of OK-432 appears to be clinically superior to intramuscular injection.

Adjuvants, Immunologic↗
PubMed1984

Effect of homologous delayed hypersensitivity testing on specific and non-specific lymphoblastic transformation in cattle latently infected with bovine rhinotracheitis virus (bovine herpesvirus 1, BHV 1).

Two cattle latently infected with infectious bovine rhinotracheitis virus (Bovine herpesvirus 1, BHV 1) were intradermally injected with inactivated BHV 1 antigen (delayed hypersensitivity test, DHT, skin test). Another animal, free of BHV 1 infection was similarly treated. Two latent carriers of the virus, intradermally injected with Phosphate-Buffered Saline solution were used as control. The evolution of spontaneous multiplication of lymphocytes and lymphoblastic transformation in vitro induced by three phytomitogens (con A, PHA, PWM) and BHV 1 antigen was followed in all animals. The delayed hypersensitivity test provoked an increase in spontaneous lymphocyte multiplication in latent carriers as well as an increase in mitogen- and antigen-induced blastogenesis on the 2nd and the 9th day following the treatment. A similar increase occurred on the 9th day in the BHV 1-free animal. Therefore, in latent carriers of BHV 1, delayed hypersensitivity testing induces an anamnestic lymphocyte reaction corresponding to the cutaneous one. This first lymphocyte activity is followed, one week later, by a new reaction which occurs both in infected and uninfected animals.

Animals↗
PubMed1983

Epidermal cell proliferation following an active arthus reaction in the guinea pig.

Active Arthus reactions were provoked by injections of 100 micrograms horseradish peroxidase (HRP), 10 micrograms HRP and 100 micrograms bovine serum albumin (BSA) into the skin of sensitized guinea pigs. Labeling indices (LI) of epidermal basal cells were measured 1, 4, 8, 24, 48 and 72 h later by the in vivo 3H-thymidine labeling technique, and compared with those obtained with injections of antigens into the skin of non-sensitized guinea pigs. From 1-8 h after the induction of an active Arthus reaction, the LI of epidermal basal cells of the skin injected with 100 micrograms HRP decreased to a remarkably low value. On the other hand, those obtained with the reaction against 10 micrograms HRP were significantly high. At 24 h after the reaction, LI were as high as those obtained in non-sensitized guinea pigs with control intradermal injections, though the former persisted high until 48 h after the injection. In addition, decreased LI of the epidermal basal cells were observed in the skin 4 h after intradermal injections of immune complexes. It was suggested that DNA synthetic activity of the epidermis increases in a mild active Arthus reaction, while the activity may be suppressed in a severe active Arthus reaction up to 8 h after provocation.

Animals↗
PubMed1972

Studies on normal and immune lymphocyte transfer reactions in guinea pigs, with special reference to the cellular contribution of the host.

Using guinea pigs of strains 2 and 13 and their F(1) hybrids as experimental subjects, various lines of evidence have been obtained that in this species, as in all others tested, the only significant cellular antigens with which donor lymphocytes engage when normal and immune lymphocyte reactions are incited are radiosensitive leukocytes. Constitutive cells of the skin are unimportant. (a) The intensities of these reactions in irradiated subjects are dependent upon the peripheral leukocyte concentration. When this falls below a certain threshold no reactions are incitable. (b) Highly leukopenic animals are capable of developing immune lymphocyte transfer (ILT) reactions if normal lymphoid cells of their own genetic constitution are mixed with the putative attacking donor cells, as "supplementing antigen," before inoculation. (c) Radiation-chimeric strain 13 animals having F(1) hybrid leukocytes in their bloodstream give typical ILT reactions when challenged intradermally with strain 13 anti-2 node cells. Exposure of strain 2 animals to 600 R does not prevent their becoming actively immunized if, 24 hr later, they are injected intradermally with strain 13 lymphocytes. However, this sensitization, revealed by the host's capacity to give delayed hypersensitivity reactions, wanes as leukopenia progresses. On the basis of this and other findings it is argued that the flare-up stage of the NLT reaction in preirradiated hosts is mainly an expression of host sensitivity against the transferred alien cells. Two unexpected observations have been made in the course of this study: (a) F(1) hybrid animals developed what appeared to be a strong delayed hypersensitivity after intradermal inoculation with parental strain lymphoid cells or antigenic extracts prepared from them. (b) If strain 13 guinea pigs which had been sensitized against strain 2 tissue antigens by intradermal injection of lymphocytes 7 days beforehand were inoculated intravenously with strain 2 antigenic extract a significant proportion of the animals developed severe delayed necrotizing reactions, recall flares, at some or all of the healed skin inoculation sites.

Animals↗
PubMed1976

Sugar polymers in rats and man.

Intracutaneous injections of a glucan contaminant of invert sugar solutions and crude cane sugar into human skin produced a localised wheal and erythema reaction. The glucan was also active on intradermal injection into both dextran-sensitive and dextran-resistant rats.

Animals↗
PubMed2006

[Sarcoidal granulomas following injections of botulic toxin A (Botox) for corrections of wrinkles].

BACKGROUND: The introduction of foreign material into the skin can lead to sarcoidal reactions. Such a reaction is reported, consecutive to injections of botulic toxin A (Botox). CASE REPORT: A 57-year-old woman, noticed the occurrence of frontal and glabellar nodules, 3 weeks after the injection of botulic toxin A (Botox), for the correction of wrinkles. Histopathological examination revealed a sarcoidal granuloma. Clinical and biological investigations were negative, ruling out the hypothesis of systemic sarcoidosis. The lesion could be reproduced experimentally by an intradermal injection of botulic toxin A on the volar aspect of the forearm. Corticosteroids per os associated with intralesional injections of triamcinolone acetonide were followed by a complete regression of the nodules. DISCUSSION: The occurrence of sarcoidal granulomas at the sites of injection of botulic toxin A (Botox(R)) has not been reported - so far - in the literature. Systemic sarcoidosis has been ruled out. The sarcoidal reaction has been reproduced experimentally by the intradermal injection of botulic toxin A, but not by saline. This leads to think that the sarcoidal reaction was provoked by antigenic stimulation, comparable to the Kveim reaction, and did not correspond to "scar sarcoidosis".

Botulinum Toxins, Type A↗
PubMed1999

Live confocal microscopy of oligonucleotide uptake by keratinocytes in human skin grafts on nude mice.

Anti-sense oligonucleotide uptake by keratinocytes in human skin grafts on athymic mice was examined using live confocal microscopy. Fluorescein isothiocyanate-labeled 15-mer C-5 propyne modified phosphorothioate anti-sense oligonucleotide (10-50 microM) was intradermally injected into normal human skin grafts on athymic mice, and the localization of the anti-sense oligonucleotide was assessed after 1-24 h postinjection. Anti-sense oligonucleotide was found to localize in the nuclei of basal and suprabasal keratinocytes after 1-2 h, and this localization was still observed after 24 h. This live in vivo observation of anti-sense oligonucleotide uptake in basal keratinocytes was confirmed using conventional fluorescence microscopy of fixed sections of skin grafts. Neither single nucleotides which were fluorescein isothiocyanate-labeled nor fluorescein isothiocyanate alone was able to penetrate into the nuclei of human skin graft keratinocytes after intradermal injection, and hence it is likely that the anti-sense oligonucleotide was not degraded prior to intracellular localization. Topical administration of anti-sense oligonucleotide and anti-sense oligonucleotide-liposome complexes resulted primarily in localization in the stratum corneum of human skin grafts. When grafts were tape stripped prior to anti-sense oligonucleotide administration, however, as little as 5 microM anti-sense oligonucleotide was required to observe nuclear anti-sense oligonucleotide accumulation. These results suggest that cutaneous anti-sense strategies can be tested using delivery via intradermal anti-sense oligonucleotide injection in human skin grafts on athymic mice, and that agents providing penetration of anti-sense oligonucleotide across the stratum corneum are likely to be required for successful topical therapies.

Administration, Topical↗
PubMedDate not supplied

Botulinum toxin in the treatment of axillary hyperhidrosis.

INTRODUCTION: Axillary hyperhidrosis can be a source of social isolation and embarrassment. The available treatments are either ineffective or have intolerable side effects. The search for a simple, long-lasting, and safe treatment has led to the use of botulinum-A toxin injections in those with excessive axillary hyperhidrosis. MATERIALS AND METHODS: Fifteen patients participated in this study. All had a history of axillary hyperhidrosis of 1-6 years duration and were using different types of therapies without any benefit. Each patient was injected intradermally with 125 units of botulinum-A toxin (Dysport, Spenywood Pharmaceutical) in 5-6 points over an elliptical area on each side. Patient follow-up was performed using the iodine-starch test. RESULTS: A total of 14 out of the 15 patients had complete anhidrosis 1 week after the injection. This result lasted for periods ranging from 1-6 months. No side effects were encountered. CONCLUSION: Intradermal injection of botulinum-A toxin seems to be a safe, rapid, and effective method of treatment in axillary hyperhidrosis.

Adolescent↗
PubMedDate not supplied

Factors influencing immediate responses to intradermal allergen administration in patients with respiratory allergy.

BACKGROUND: Immediate skin reactions to allergens are influenced by several factors, such as the amount of administered allergen, the level of specific IgE, releasability of mast cells and hyperresponsiveness of the target organ. METHODS: For the evaluation of factors influencing immediate skin response to intradermal allergen administration, we measured the wheal size 15 min after intradermal injection of 0.01-0.02 ml of the following agents: whole-body extract of Dermatophagoides farinae, 1,000 allergy units/ml; histamine, 0.1 mg/ml, and codeine sulfate, 0.09% in saline, and determined total IgE level, specific IgE and IgG subclass antibodies to D. farinae in 53 patients with respiratory allergy. RESULTS: Multiple regression analysis for factors influencing wheal size after intradermal injection of D. farinae, specific IgE antibody level to D. farinae and wheal size after intradermal administration of histamine showed statistically significant results (R2 = 0.42739, p = 0.0000; R2 = 0.50243, p = 0.0185, respectively). Multiple regression analysis for factors influencing wheal size after intradermal administration in the group with high levels of specific IgE to D. farinae (RAST class 3 or more) showed that wheal size after intradermal administration of codeine was the only factor exerting a statistically significant influence (p = 0.0119). CONCLUSION: Based on the above results, we can state that immediate responses to intradermal allergen administration were influenced by the level of specific IgE and hyperresponsiveness of the target organ to histamine, but that the immediate skin allergic responses in the presence of high levels of specific IgE were partially but significantly influenced by the releasability of skin mast cells.

Adult↗
PubMed1986

Observations on dermal blood flow as reflected by technetium-99m pertechnetate clearance.

Skin blood flow as reflected by the clearance rate of intradermal injections of Technetium-99m (99mTc) was studied in the skin of human volunteers and in a variety of clinical situations. In volunteers comparisons between the effect on clearance following intradermal injections of either lignocaine or lignocaine/adrenaline showed that the latter resulted in a dramatic reduction in the clearance rate of the technetium isotope and that such clearance curves exhibited no fast component. Clinical studies in grossly ischaemic skin revealed a similar absence of the fast component of isotope clearance and this was also the case for healed split thickness skin grafts. The dermal isotope clearance was also used in pedicle skin flaps both before and after clamping the axial pedicle in order to derive clearance ratios which would reflect the degree of neovascularisation to the flap. These preliminary observations suggest that the technique is safe, and easy to use in many clinical circumstances. We consider that it offers a valuable method by which changes in dermal blood flow may be quantified, when simultaneous control areas of isotope clearance are also studied. Suggestions are made for further avenues of study.

Adult↗
PubMed2001

Modified short-term guinea pig sensitization tests for detecting contact allergens as an alternative to the conventional test.

The conventional adjuvant and patch test (APT) method of guinea pig sensitization testing was modified in 2 ways, s-APT and s-APT(2), in order to shorten the test period. These short-term test methods consist of 72-h closed application of test material with intradermal injection of emulsified Freund's complete adjuvant (E-FCA) for 1st induction, 48-h closed application of test material with (s-APT) or without (s-APT(2)) intradermal injection of E-FCA on the 7th day for 2nd induction, and open application on the 14th day for challenge. They were compared with conventional APT by using 8 allergenic chemicals (formaldehyde, nickel sulfate, cobalt sulfate, ethyl-p-aminobenzoate (benzocaine), isoeugenol, 2-mercaptobenzothiazole, 2,4-dinitrochlorobenzene (DNCB) and 1-phenylazo-2-naphthol (Sudan I)). The short-term methods gave similar results to those of conventional APT in terms of mean response, sensitization rate and sensitization potency (challenge concentration that induces a mean response equal to 1.0). Thus, our short-term methods, which are capable of evaluating skin sensitization within 17 days, are sufficiently sensitive to detect potentially hazardous contact allergens.

Allergens↗
PubMed1993

Development and transfer of immediate cutaneous hypersensitivity in mice exposed to aerosolized antigen.

We previously showed that BALB/c mice sensitized to ovalbumin (OVA) by brief daily inhalations of antigen over 10 consecutive days exhibit elevated antigen-specific serum IgE antibody levels and increased airways responsiveness. For the first time, we now show that animals sensitized in this fashion to either OVA or ragweed (RGW) develop immediate hypersensitivity skin test reactions when challenged 2 d after completion of the sensitization protocol. Skin testing, performed by direct assessment of wheal formation after intradermal injection of allergen, was sensitive and specific, since animals exposed to RGW by inhalation only responded to RGW, and OVA-sensitized animals responded only to OVA. Positive reactions were associated with mast cell degranulation, whereas control injections were not. Since only sensitized IgE high responder BALB/c mice but neither nonsensitized BALB/c mice nor OVA-sensitized IgE low responder SJL/J mice exhibited wheal responses, induction of OVA-specific IgE appeared to be essential for the mediation of OVA-specific immediate hypersensitivity reactions of the skin in this model. Passive cutaneous anaphylaxis (PCA) testing confirmed the presence of antigen-specific IgE in the serum. Mice that developed IgG (predominantly IgG2b) anti-OVA antibodies did not respond to OVA injection, indicating that OVA-specific IgG was not involved in this system. Further support for the role of IgE in the immediate hypersensitivity response included the wheal response to intradermal injection of anti-IgE antibody that occurred in OVA- and RGW-sensitized mice at 10-fold lower concentrations than in nonsensitized BALB/c mice and not in sensitized SJL/J mice. After transfer of mononuclear cells from peribronchial lymph nodes of OVA- or RGW-sensitized BALB/c mice, naive, syngeneic recipients developed antigen-specific IgE and specific immediate hypersensitivity responses, indicating that the local lymphoid tissue at the site of sensitization can transfer responsiveness to these allergens. These results demonstrate for the first time the ability to elicit and study IgE-mediated immediate skin hypersensitivity responses in the mouse and illustrate the association of increased antigen-specific and total serum IgE levels, airways hyperresponsiveness, and antigen-specific immediate cutaneous reactivity after sensitization to allergen via the airways.

Aerosols↗
PubMed2000

Modulating specific priming of immune effector functions by DNA-based vaccination strategies.

We have used the hepatitis B virus system in mice to investigate under which conditions the different DNA delivery techniques used in DNA vaccination introduce a T2 or T1 bias into the responses they elicit. Priming mice by an intramuscular injection of 100 microg plasmid DNA stimulated long-lasting T1 immune responses that included specific activation of potent MHC-1-restricted CTL responses. In contrast, priming mice with an intradermal injection of a low dose of plasmid DNA (0.1-1 microg/mouse) stimulated long-lasting T2 immune responses but no CTL responses. This polarization (spectrum of immune effector specificities) of immune responses elicited by plasmid DNA vaccines is determined by different factors, e.g. (i) the vaccination technique used; (ii) the age of the immunized animal; (iii) the condition of the local tissue environment to which DNA is delivered; (iv) the co delivery of immune-modulating factors; and (v) the type of antigen encoded by the plasmid DNA vaccine. DNA vaccination offers the possibility of constructing endogenous, chimaeric antigens with enhanced, hsp-facilitated expression, enhanced immunogenicity for B cells, and alternative, TAP-independent processing for MHC-1 restricted peptide presentation.

Adjuvants, Immunologic↗
PubMed1987

Leukotriene and prostaglandin sensitization of cutaneous high-threshold C- and A-delta mechanonociceptors in the hairy skin of rat hindlimbs.

Single C- and A-delta fibers were isolated from dissected filaments of the saphenous nerve in pentobarbital anesthetized rats and the corresponding cutaneous receptive fields mapped with calibrated von Frey hairs. Nociceptors were characterized by their responses to noxious mechanical, thermal and chemical stimuli, including intradermal injections of leukotriene B4, prostaglandin E2, bradykinin and capsaicin. Leukotriene B4 decreased the mean mechanical threshold by a maximum of 80% within 10 min and for more than 3 h after intradermal injection of 75 ng of leukotriene B4. The degrees of sensitization of a fiber by leukotriene B4 and prostaglandin E2 were highly correlated. A potentiation effect also was observed, in that injection of prostaglandin E2 or leukotriene B4 1 h after the other eicosanoid further lowered the mechanical threshold of a sensitized fiber, whereas fibers that were not sensitized by leukotriene B4 were unaffected by prostaglandin E2. The sensitizing action of leukotriene B4 and prostaglandin E2 was directed to multiple classes of cutaneous nociceptors including 73% of C-polymodal, 60% of C-mechano-heat, 42% of C-mechano-cold nociceptors and 70% of A-delta high-threshold mechanonociceptors. The pain-evoking substances bradykinin and capsaicin activated 81% and 88%, respectively, of the sensitized C-polymodal nociceptors, 17% and 84% of the sensitized-C-mechano-heat nociceptors, 12% and 37% of the sensitized C-mechano-cold nociceptors, and 17% and none of the sensitized A-delta high-threshold mechanociceptors. The responses of C-fibers to bradykinin and capsaicin were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗