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PubMed1994

A psychophysical study of secondary hyperalgesia: evidence for increased pain to input from nociceptors.

Substantial evidence suggests that the hyperalgesia to mechanical stimuli that occurs in an area of uninjured skin surrounding a site of injury (area of secondary hyperalgesia) arises from activity in low-threshold mechanoreceptors (LTMs). In this study, we have investigated if activity in mechanically sensitive nociceptors also contributes to this secondary hyperalgesia. It is known that all woollen fabrics excite LTMs, but that only the prickly ones activate mechanically sensitive nociceptors. Therefore, we have conducted a psychophysical study using a range of prickly and non-prickly woollen fabrics applied to normal and hyperalgesic skin to assess the roles of LTMs and nociceptors in secondary hyperalgesia. We have studied in 10 normal volunteers the sensations of fabric-evoked prickle and pain in normal and hyperalgesic skin. Secondary hyperalgesia was produced by intradermal injection of capsaicin (25 micrograms) into the volar skin of the forearm. Five woollen fabrics (2 non-prickly, 2 prickly and 1 intermediate) were presented, in a blind manner, to the skin before and after the capsaicin injection. The sensation of fabric-evoked prickle was not changed in hyperalgesic skin. On the other hand, little if any pain was evoked by the fabrics when applied to normal skin, but substantial pain was produced by all fabrics when applied to hyperalgesic skin. The pain ratings were graded with the ratings of prickle so that fabrics that evoked the greatest prickle also evoked significantly more pain. The magnitude of pain increased linearly with prickle sensation; the slope of this regression function increased substantially in hyperalgesic skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Peripheral administration of nerve growth factor in the adult rat produces a thermal hyperalgesia that requires the presence of sympathetic post-ganglionic neurones.

Previous evidence suggests that, in adult animals, nerve growth factor (NGF) can induce hyperalgesia, and may be an endogenous mediator in some persistent pain states. Here we have studied the effects of single intradermal injections of 50-500 ng of human recombinant NGF into the plantar skin of adult rat hindpaws. We found that doses of 250 ng and more produced a prolonged and stable thermal hyperalgesia to radiant heat. NGF did not produce overt pain behaviour as judged by the absence of paw licking or guarding of the injected paw. In animals subjected to surgical or chemical sympathectomy, by repeated systemic guanethidine treatments, the hyperalgesic effects of NGF were markedly reduced. We also found that NGF produced plasma extravasation in rat skin, using the Evan's blue method, with a dose dependency similar to that determined for hyperalgesia. Together, these findings suggest that NGF can lead to a rapid activation and sensitization of cutaneous nociceptors. However, these actions appear at least partly indirect, requiring the presence of normal sympathetic post-ganglionic terminals.

Animals↗
PubMed1990

Direct cutaneous hyperalgesia induced by adenosine.

The intradermal injection of adenosine produces a dose-dependent decrease in mechanical nociceptive threshold in the hindpaw of the rat that is not attenuated by elimination of indirect pathways for the production of hyperalgesia. Adenosine-induced hyperalgesia is mimicked by the A2-agonists, 5'-(N-ethyl)-carboxamido-adenosine and 2-phenylaminoadenosine but not by the A1-agonist, N6-cyclopentyladenosine and antagonized by the adenosine A2-receptor antagonist, PD 081360-0002 but not by the A1-antagonist, 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine. The latency to onset of adenosine and 2-phenylaminoadenosine hyperalgesia is similar to that produced by prostaglandin E2, a directly acting hyperalgesic agent but shorter than that produced by leukotriene B4, which acts indirectly. 2-Phenylaminoadenosine hyperalgesia is prolonged by rolipram, a phosphodiesterase inhibitor. Both 2-phenylaminoadenosine and prostaglandin E2 hyperalgesia are antagonized by the A1-agonist N6-cyclopentyladenosine and the mu-agonist, [D-Ala2, NMe-Phe4, Gly-ol]enkephalin. However, 1-acetyl-2-(8-chloro-10,11-dihydrodibenz[b,f]oxazepine-10-ca rbonyl) hydrazine, a prostaglandin-receptor antagonist, inhibits prostaglandin E2 (Taiwo and Levine, Brain Res. 458, 402-406, 1988) but not 2-phenylamino-adenosine hyperalgesia and PD 081360-0002, the adenosine receptor antagonist, inhibits 2-phenylamino-adenosine but not prostaglandin E2 hyperalgesia. These data suggest that adenosine is a directly acting agent that produces hyperalgesia by an action at the A2-receptor and that this hyperalgesia is mediated by the cAMP second messenger.

Adenosine↗
PubMed1992

The role of Haemophilus ducreyi bacteria, cytotoxin, endotoxin and antibodies in animal models for study of chancroid.

Haemophilus ducreyi cytotoxin-positive and -negative strains as well as bacterial sonicates and lipooligosaccharides (LOS) from such strains were evaluated for the capacity to produce dermonecrotic lesions, especially ulcers, after intradermal injections to rabbits and to different mouse strains, including nude mice. Dermonecrotic lesions of the ulcerous type were observed within 4 days and they were developed in both rabbits and mice with about 10(7) colony forming units (cfu) of H. ducreyi. Viable bacteria were isolated from the lesions up to 9 days after inoculation. All lesions healed spontaneously within 2-3 weeks. Bacterial sonicate (heated and unheated) and LOS preparations caused mainly abscess formation in rabbits, while in mice, a superficial, haemorrhagic ulceration was observed. To obtain ulceration at all injection sites, about 200 micrograms of LOS was required. Histological examination of acute, dermonecrotic lesions caused by viable bacteria showed deep necrosis, infiltrate of inflammatory cells, especially granulocytes and dilatation of blood vessels. The same type of inflammatory cells as seen in lesions caused by bacteria, were involved in the mouse lesions caused by bacterial sonicate and LOS preparations. The results indicate that LOS/endotoxin, probably in combination with other bacterial polysaccharides, can play a role in ulceration caused by H. ducreyi in animals; however, a relatively high amount of LOS preparation was necessary to cause dermal ulceration at all injection sites in the mouse model. The development of ulcers correlated with the endotoxin activity in bacterial sonicate and in LOS preparations. The model may therefore be useful to study the role of LOS components in development of ulceration. There was no significant difference in lesions caused by cytotoxin producing, respectively, non-producing H. ducreyi strains and cell-free preparations from such strains. The bacterial sonicates, cytotoxic for human cell lines, failed to kill animal cell lines, indicating that animal models do not adequately reflect the cytotoxin activity in experimental H. ducreyi infection. Antibodies to H. ducreyi sonicate and LOS, tested by means of ELISA, were found in pre-immune sera from both rabbits and mice. There was a significant antibody response to homologous cell sonicate and LOS, after primary and secondary infections with bacteria. Still, there was no clear difference between primary and secondary lesions in animals. Since animal lesions are mainly due to endotoxin activity, this may indicate that antibodies are of minor importance for protection in animal models.

Abscess↗
PubMedDate not supplied

Use of botulinum toxin to treat blepharospasm in a 16-year-old with a dystonic syndrome.

A 16-year-old boy with generalized dystonia had continuous, severe blepharospasm and facial grimacing. Local intradermal injections of botulinum A toxin greatly reduced the spasms and improved function. No side effects were observed. Local botulinum A toxin injections may be useful in the treatment of eyelid and facial spasms in patients with generalized dystonias.

Adolescent↗
PubMed1991

Adjuvant oils induce arthritis in the DA rat. I. Characterization of the disease and evidence for an immunological involvement.

An intradermal injection of Freund's incomplete adjuvant oil (FIA) without further additives was shown to induce erosive polyarthritis in dark Agouti (DA) rats, but not in Lewis rats. Histological examination revealed joint inflammation, first with polymorphonuclear cells and synovial hyperplasia, and subsequently, with multinucleated giant cells. Both constituents of FIA, mineral oil and Arlacel A, as well as Pristane oil were arthritogenic, whereas vegetable oil were not. Re-administration of adjuvant oil after recovery failed to induce arthritis, thus making possible a role of specific immunity in this new form of arthritis in rats.

Adjuvants, Immunologic↗
PubMed1992

Contact hypersensitivity reaction to ovalbumin in newborn guinea pigs from maternally sensitized animals.

An animal study was conducted to elucidate the role of ovalbumin (OA) in the development of eczematous lesions in intrauterine sensitized newborns. Four groups of pregnant guinea pigs were used: group A, immunized by oral administration of 1% OA in drinking water until parturition; group B, immunized by intradermal injection of OA with Freund's complete adjuvant; group C, immunized by both methods; and group D (control), not immunized. The newborn guinea pigs of each group were patch tested with 10% OA in white petrolatum. Positive reactions were seen in the newborns of groups B and C, but not in those in groups A and D. By enzyme-linked immunosorbent assay and passive cutaneous anaphylaxis, a high titre of OA-specific IgG was detected in the group B and C newborns. The number of positive patch test reactions decreased concomitantly with the decline of specific IgG. Histologically, eczematous changes were observed in the positive reaction sites. Many OA antigen-bearing Langerhans cells were found by the immuno-double labelling technique. Immuno-electron microscopic findings revealed the presence of OA antigens as well as IgG molecules on the cytoplasmic membranes of Langerhans cells. Our studies demonstrated that maternal sensitization with OA can induce an eczematous reaction in the newborns to OA patch testing under the presence of high levels of OA-specific IgG in the serum. From these findings it is suggested that IgG plays an essential role in the development of contact hypersensitivity reaction to OA.

Administration, Oral↗
PubMed1995

Adjuvant-induced persistent photosensitivity models in guinea pigs. I. Induction of persistent photosensitivity.

Induction of persistent photosensitivity in guinea pigs was carried out in an attempt to induce a model suitable to clarify the mechanism of human persistent light reactors. Guinea pigs were treated with intradermal injection of adjuvant which consisted of desiccated Mycobacteria followed by topical application of hapten solution and irradiation with UVA. Unequivocal skin reactions were subsequently elicited with UVA exposure in the absence of hapten application. This enhanced UVA reactivity persisted and could be elicited for more than 2 years. In these guinea pigs, remarkably increased sensitivity to UVB was also observed. These animals appear quite similar to persistent light reactors among humans. Muramyl dipeptide used in place of Mycobacteria was also found to be effective in inducing photosensitivity to UVA. There were great differences of reactivity noted among different strains of guinea pig, suggesting that persistent photosensitivity is influenced by genetic background. Enhanced UV sensitivity was induced without hapten application, only with injections of adjuvant and UVA irradiation in the immunization procedure. These results suggest that this model will be useful to study chronic actinic dermatitis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Assessment of blood flow changes at multiple sites in rabbit skin using a 133Xenon clearance technique.

133Xenon clearance represents a clinically useful method of measuring local circulatory function in a variety of different tissues. The method detailed in this article describes how the 133Xenon clearance technique can be adapted to simultaneously measure cutaneous blood flow, over a 15-min period, at a large number of skin sites within the same animal. Blood flow changes are measured in response to intradermally injected vasoactive test agents. The multisite injection plan which forms part of the method removes bias due to site variations and generates data that can be analysed statistically. Results are expressed as the percent change in 133Xenon clearance at test agent-injected sites as compared to control, saline-injected sites. The method provides an accurate and time-efficient measure of skin blood flow. In the present study, the technique is used to assess the receptor-mediated mechanism of action of the vasodilator calcitonin gene-related peptide (CGRP) and the possibility that the vasoconstrictor endothelin-1 acts to stimulate the release of vasodilator quantities of endogenous CGRP.

Animals↗
PubMed2005

[French paediatrician and general practitioner's survey about actual and future BCG use].

Within the context of future multipuncture withdrawal, we managed, in April 2005, a survey on BCG vaccine habits. During April 2005, 636 paediatricians and 192 GP took part in a survey about BCG, practices managed by InfoVac-France, InVS and AFPA. Most of physicians (73.6%) don't use Mantoux test before BCG vaccination in children less than 6 months old, and the Monovax is the most frequent vaccine used (93.7%). Less than 30% physicians are thinking to be ready to systematically vaccine children after prospected withdrawal of multipuncture vaccination, and almost 1 pediatrician of 5 and one GP of 7 don't want to vaccine anymore. In future, preferred option after Monovax withdrawal is to vaccinate with BCG only the high risk population for tuberculosis (59%). About 60% physicians think that parents could be opposed to intradermal immunization. More than 2/3 of physicians have not an assistant (except the parents) to contain the children during the intradermal injection (71.6%). It seems not acceptable for 2/3 of physicians to address their patients to colleagues or to specialized structures.

Adult↗
PubMed2006

Intradermal pregnenolone sulfate attenuates capsaicin-induced nociception in rats.

We have previously shown that the neurosteroid pregnenolone sulfate (PS) inhibits the capsaicin receptor-mediated current in rat dorsal root ganglion neurons. Here, we examined the effect of intradermal injection of PS into the rat hindpaw on capsaicin-induced nociception. Results revealed that PS co-injected with capsaicin dose-dependently inhibited the capsaicin-induced nocifensive response. In contrast, injections of PS into one hindpaw and capsaicin into the contralateral hindpaw had no effect on the capsaicin-induced nocifensive response, suggesting that PS produced its effect locally but not systemically. Moreover, PS inhibition of the capsaicin-induced nocifensive response was not significantly reduced by a nonselective opioid receptor antagonist or by cannabinoid receptor antagonists, indicating that neither an opioid- nor a cannabinoid-dependent mechanism mediated the effect of PS. These data demonstrate that PS acts peripherally to attenuate capsaicin-induced nociception through an opioid- and cannabinoid-independent mechanism and suggest a new therapeutic potential for PS in pain management.

Animals↗
PubMedDate not supplied

Inguinal, or Hexsel's hyperhidrosis.

Inguinal Hyperhidrosis (IH) is a focal and primary form of hyperhidrosis in which the individual has intense sweating in the inguinal region. It usually appears in adolescence, not later than the age of 25, in the most cases, and continues into adulthood. With a sample of 26 patients we described Inguinal Hyperhidrosis (IH). Fifty percent of the patients have a positive family history of this condition or other forms of focal or generalized hyperhidrosis, which suggests a familial pattern. Biopsies performed on the inguinal area in a patient with IH and control patient showed normal histology. Excessive perspiration in the inguinal area significantly affects the quality of life of the patients. It is an embarrassing condition that produces large wet stains on the clothes, therefore making daily activities difficult and compromising the emotional, professional and social life of the affected patients. The therapies commonly used for other forms of focal hyperhidrosis are not yet referred in the literature specifically for IH. Intradermal injections from botulinum toxin provide positive results for the patients and controls the sweating for 6 months or more. It is a simple, safe and effective treatment for this condition and the results significantly improve the quality of life of the affected individuals.

Botulinum Toxins, Type A↗
PubMed2006

Use of lidocaine-prilocaine patch for the mantoux test: Influence on pain and reading.

A formulation of a eutectic mixture of lidocaine-prilocaine (EMLA) changes basal skin perfusion. Its use for alleviating pain associated with the Mantoux test may modify the recruitment of sensitised lymphocytes and then the response to tuberculin test. Twenty-four healthy BCG-vaccinated volunteers (26.7+/-4.1 years) received on each forearm an intradermal injection of 10IU tuberculin, one of the forearms being randomly pre-treated for 1h with EMLA-patch 5%. Pain associated with the Mantoux test was evaluated using a visual analogue scale. The transversal diameter of the induration was read at 72h. Subjects with 6mm difference between diameters (i.e. twice the usual variation for a Mantoux test) were recorded. Results were compared using a paired t-test. When using lidocaine-prilocaine prior to the test, a three-fold decrease in pain was noted (p<0.0001). Reading of the test were not affected by the lidocaine-prilocaine application (p=0.26). Four subjects had 6mm or more difference between their two tests, two of them having an induration greater than 15mm with lidocaine-prilocaine. Lidocaine-prilocaine reduces significantly pain associated with the Mantoux test but does not normally affect the test reading. However, when the induration is more than 15mm, a control without lidocaine-prilocaine has to be considered.

Adult↗
PubMed2006

Decreasing the pain of local anesthesia: a prospective, double-blind comparison of buffered, premixed 1% lidocaine with epinephrine versus 1% lidocaine freshly mixed with epinephrine.

BACKGROUND: Local anesthetics are acidic and cause pain on infiltration into the skin. Two methods are commonly used by dermatologists to raise the pH of lidocaine with epinephrine: buffering with sodium bicarbonate or freshly mixing lidocaine with epinephrine on the day of use. OBJECTIVE: Our purpose was to compare the pain induced by infiltration of the skin with 1% lidocaine with epinephrine 1:100,000 buffered with sodium bicarbonate (buffered) versus 1% lidocaine freshly mixed with epinephrine (fresh). METHODS: Sixty volunteers were recruited for this prospective, double-blind study. Each subject received an intradermal injection of the buffered solution and the fresh solution. Immediately after each injection subjects rated the pain of infiltration on a 100-mm visual analog scale. The pain scores for the anesthetic solutions were compared using the paired t test. RESULTS: The pain score for the buffered solution was 18.3 +/- 20.3, and the pain score for the fresh solution was 23.5 +/- 19.1 (P = .0543). Sixty-five percent of subjects felt the fresh solution was more painful than the buffered solution. LIMITATIONS: The results did not reach statistical significance. CONCLUSION: In this small study, buffered lidocaine with epinephrine caused less pain on infiltration into the skin than lidocaine freshly mixed with epinephrine, but the results were not statistically significant.

Anesthetics, Local↗
PubMed2006

Crucial role of fibroblast integrins alpha2 and beta1 in maintaining the structural and mechanical properties of the skin.

BACKGROUND: In vivo functions of integrins in dermis have been investigated using several types of genetically integrin deficient mice. However, there are few studies to clarify actual in vivo functions of integrins in the dermis using normal type animals. OBJECTIVE: We investigated the actual in vivo functions of integrins in maintaining structural and mechanical properties in the normal skin by means of blocking interactions between fibroblasts and the extracellular matrix (ECM). METHODS: Intradermal injection of anti-integrin alpha2 or beta1 antibody into hairless rat skin was used to block the function of integrins. The dermal thickness was measured by an ultrasound scanner and the elastic properties of the skin was measured by Cutometer. RESULTS: Blocking integrin alpha2 or beta1 alone caused a moderate increase in dermal thickness. Blocking of integrins alpha1, alphaL or beta2 alone or blocking both integrins alpha1 and beta1 did not cause any change in the skin. However, blocking of both integrins alpha2 and beta1 caused a significant increase in dermal thickness accompanied by a marked loss of elastic properties. A clear change of the skin was observed within several minutes after injection, and continued for several hours. Treatment of human skin fibroblasts in collagen gel lattices with a mixture of anti-integrin alpha2 and beta1 antibodies in vitro caused marked and rapid morphological changes, but significant change was not observed with a treatment of alpha1, alpha2 or beta1 antibody alone. CONCLUSION: These results indicate that simultaneous functioning of integrins alpha2 and beta1 in fibroblasts play a crucial role in maintaining the structural and mechanical properties in the skin, which suggests that fibroblasts actively regulate collagen networks via these integrins.

Animals↗
PubMed2005

Analysis of epidermal entry in experimental cutaneous Bacillus anthracis infections in mice.

Cutaneous infection is the most common form of human anthrax, but little is known of Bacillus anthracis-epidermal interactions. To study the latter, we used experimental inoculations of B. anthracis Sterne spores onto mouse flank skin. In DBA/2 mice (a sensitive strain) 10(7) spores injected intradermally or applied under occlusive dressings to abraded skin produced ipsilateral inguinal edema and rapid death. Epicutaneous application to shaved-only skin produced edema and death in most animals, but at longer times. Mortality after inoculation onto abraded skin was less in C57BL/6 mice (a relatively resistant strain). Inoculations onto shaved-only skin immunized C57BL/6 mice, and they survived later intradermal spore injections. Histology revealed massive organism proliferation in remaining epidermis and hair follicles of inoculated abraded skin, but less growth in the dermis itself. Conversely, no foci could be located by microscopic examination after inoculation onto shaved-only skin. High-dose nonocclusive dressing inoculations onto unshaved skin in DBA/2 mice revealed small numbers of infective foci, all in hair follicles. These results suggest that epidermal damage may increase infection susceptibility to B. anthracis of hair follicle contents and remaining epidermal remnants; the findings also indicate that access may occur through hair follicles and the denuded dermis.

Animals↗
PubMed2006

Capsaicin-evoked brain activation and central sensitization in anaesthetised rats: a functional magnetic resonance imaging study.

Functional magnetic resonance imaging (fMRI) of blood oxygen level dependent (BOLD) haemodynamic responses was used to study the effects of the noxious substance capsaicin on whole brain activation in isofluorane anaesthetised rats. Rats (n=8) received intradermal injection of capsaicin (30 microg/5 microl), or topical cream (0.1%) capsaicin and BOLD responses were acquired for up to 120 min. Effects of capsaicin versus placebo cream treatment on the BOLD response to a 15 g mechanical stimulus applied adjacent to the site of cream application were also studied. Both injection and cream application of capsaicin activated brain areas involved in pain processing, including the thalamus and periaqueductal grey (PAG) (p<0.05, corrected for multiple comparisons). Capsaicin also produced increases in BOLD signal intensity in other regions that contribute to pain processing, such as the parabrachial nucleus and superior colliculus. Mechanical stimulation in capsaicin-treated rats, but not placebo-treated rats, induced a significant decrease in BOLD signal intensity in the PAG (p<0.001). These data demonstrate that the noxious substance capsaicin produces brain activation in the midbrain regions and reveals the importance of the PAG in central sensitization.

Administration, Topical↗
PubMed2006

Enhanced antigen-specific antibody production following polyplex-based DNA vaccination via the intradermal route in mice.

DNA vaccination is an attractive approach with various advantages over conventional vaccination. The present study was undertaken to examine whether polyplex-based DNA vaccination could be used to modulate immune responses by plasmid DNA (pDNA). Methylated bovine serum albumin (mBSA) was used as a model of a cationic macromolecular carrier of pDNA encoding obalbumin (OVA) and the effects of polyplex formation of pDNA with mBSA on the antigen-specific immune responses were examined. Anti-OVA IgG antibody production was significantly increased following intradermal immunization with the polyplex compared with naked pDNA, although the induction of cytotoxic T lymphocyte activity was lowered by polyplex formation. We also demonstrated that the disposition and gene expression of pDNA following intradermal injection could be manipulated by polyplex formation. Intriguingly, we also found that the migration of dendritic cells to the injected site could be induced by polyplex formation probably due to a high level of tumor necrosis factor alpha production from the keratinocytes treated with mBSA/pDNA complexeses. Thus, the present study has demonstrated that the immune responses could be biased towards a Th2-type response by polyplex-based DNA vaccination through manipulation of not only pDNA disposition but also dendritic cell migration.

Animals↗