Hexyl aminolevulinate, 5-aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non-aggressive basal cell carcinomas: A non-sponsored, randomized, prospective and double-blinded trial.

BACKGROUND: In the photodynamic therapy (PDT) of non-aggressive basal cell carcinomas (BCCs), 5-aminolevulinic acid nanoemulsion (BF-200ALA) has shown non-inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL-PDT in the treatment of BCCs. OBJECTIVES: To compare the histological clearance, tolerability (pain and post-treatment reaction) and cosmetic outcome of MAL, BF-200 ALA and low-concentration HAL in the PDT of non-aggressive BCCs. METHODS: Ninety-eight histologically verified non-aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED-PDT in two repeated treatments with MAL, BF-200 ALA or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post-treatment reactions fluorescence and photobleaching were evaluated. RESULTS: According to intention-to-treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9-98.3) for MAL, 90.9% (95% CI = 76.4-96.9) for BF-200 ALA and 87.9% (95% CI = 72.7-95.2) for HAL, with no differences between the arms (P = 0.84). There were no differences between the arms as regards pain, post-treatment reactions or cosmetic outcome. CONCLUSIONS: Photodynamic therapy with low-concentration HAL and BF-200 ALA has a similar efficacy, tolerability and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration.

Ablative fractional laser-assisted photodynamic therapy for lentigo maligna: a prospective pilot study.

BACKGROUND: Lentigo maligna (LM) is an in situ form of melanoma carrying a risk of progression to invasive lentigo maligna melanoma (LMM). LM poses a clinical challenge, with subclinical extension and high recurrence rates after incomplete surgery. Alternative treatment methods have been investigated with varying results. Photodynamic therapy (PDT) with methylaminolaevulinate (MAL) has already proved promising in this respect. OBJECTIVES: To investigate the efficacy of ablative fractional laser (AFL)-assisted PDT with 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) for treating LM. METHODS: In this non-sponsored prospective pilot study, ten histologically verified LMs were treated with AFL-assisted PDT three times at 2-week intervals using a light dose of 90 J/cm2 per treatment session. Local anaesthesia with ropivacaine was used. Four weeks after the last PDT treatment the lesions were treated surgically with a wide excision and sent for histopathological examination. The primary outcome was complete histopathological clearance of the LM from the surgical specimen. Patient-reported pain during illumination and the severity of the skin reaction after the PDT treatments were monitored as secondary outcomes. RESULTS: The complete histopathological clearance rate was 7 out of 10 LMs (70%). The pain during illumination was tolerable, with the mean pain scores for the PDT sessions on a visual assessment scale ranging from 2.9 to 3.8. Some severe skin reactions occurred during the treatment period, however. CONCLUSIONS: Ablative fractional laser-assisted PDT showed moderate efficacy in terms of histological clearance. It could constitute an alternative treatment for LM but due to the side effects it should only be considered in inoperable cases.

Hyperspectral imaging system in the delineation of Ill-defined basal cell carcinomas: a pilot study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the Caucasian population. Eighty per cent of BCCs are located on the head and neck area. Clinically ill-defined BCCs often represent histologically aggressive subtypes, and they can have subtle subclinical extensions leading to recurrence and the need for re-excisions. OBJECTIVES: The aim of this pilot study was to test the feasibility of a hyperspectral imaging system (HIS) in vivo in delineating the preoperatively lateral margins of ill-defined BCCs on the head and neck area. METHODS: Ill-defined BCCs were assessed clinically with a dermatoscope, photographed and imaged with HIS. This was followed by surgical procedures where the BCCs were excised at the clinical border and the marginal strip separately. HIS, with a 12-cm2 field of view and fast data processing, records a hyperspectral graph for every pixel in the imaged area, thus creating a data cube. With automated computational modelling, the spectral data are converted into localization maps showing the tumour borders. Interpretation of these maps was compared to the histologically verified tumour borders. RESULTS: Sixteen BCCs were included. Of these cases, 10 of 16 were the aggressive subtype of BCC and 6 of 16 were nodular, superficial or a mixed type. HIS delineated the lesions more accurately in 12 of 16 of the BCCs compared to the clinical evaluation (4 of 16 wider and 8 of 16 smaller by HIS). In 2 of 16 cases, the HIS-delineated lesion was wider without histopathological confirmation. In 2 of 16 cases, HIS did not detect the histopathologically confirmed subclinical extension. CONCLUSIONS: HIS has the potential to be an easy and fast aid in the preoperative delineation of ill-defined BCCs, but further adjustment and larger studies are warranted for an optimal outcome.

5-aminolaevulinic acid nanoemulsion is more effective than methyl-5-aminolaevulinate in daylight photodynamic therapy for actinic keratosis: a nonsponsored randomized double-blind multicentre trial.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) with methyl-5-aminolaevulinate (MAL) is an effective treatment for mild and moderate actinic keratosis (AK). OBJECTIVES: To assess the clinical efficacy, tolerability and cost-effectiveness of 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) compared with MAL in DL-PDT for grade I-II AKs. METHODS: This nonsponsored, prospective randomized double-blind multicentre trial included 69 patients with 767 grade I-II AKs located symmetrically on the face or scalp. A single DL-PDT was given in a randomized split-face design. The primary outcome was clearance of the AKs at 12 months as assessed by a blinded observer. The secondary outcomes were pain, treatment reactions, cosmetic outcome and the cost-effectiveness of the therapy. RESULTS: In the per-patient (half-face) analysis, clearance was better for the BF-200 ALA sides than for those treated with MAL (P = 0·008). In total, BF-200 ALA cleared 299/375 AKs (79·7%) and MAL 288/392 (73·5%) (P = 0·041). The treatment was practically painless with both photosensitizers, the mean pain visual analogue scale being 1·51 for BF-200 ALA and 1·35 for MAL (P = 0·061). Twenty-six patients had a stronger skin reaction on the BF-200 ALA side, seven on the MAL side and 23 displayed no difference (P = 0·001). The cosmetic outcome was excellent or good in > 90% of cases with both photosensitizers (P = 1·000). The cost-effectiveness plane showed that the costs of DL-PDT were similar for both photosensitizers, but the effectiveness was slightly higher for BF-200 ALA. CONCLUSIONS: Our results indicate that BF-200 ALA is more effective than MAL in DL-PDT for grade I-II AKs. BF-200 ALA provides slightly better value for money than MAL.

Clinicopathological characteristics and cell cycle proteins as potential prognostic factors in myoepithelial carcinoma of salivary glands.

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).

Daylight photodynamic therapy for actinic keratoses: a randomized double-blinded nonsponsored prospective study comparing 5-aminolaevulinic acid nanoemulsion (BF-200) with methyl-5-aminolaevulinate.

BACKGROUND: Daylight-mediated photodynamic therapy (DL-PDT) using methyl-5-aminolaevulinate (MAL) is effective for thin, grade I, actinic keratoses (AK). There are no published studies of other photosensitizers used in DL-PDT. OBJECTIVES: To compare the efficacy and adverse effects of 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) with MAL in DL-PDT of grade I-III AKs. METHODS: In 13 patients, 177 AKs were randomized symmetrically for a split-face prospective observer-blinded study and received either BF-200 ALA or MAL DL-PDT. Grade I AKs were treated once and grade II-III AKs twice with a 0·25-mm layer of photosensitizer precursors. Pain was assessed during and after the daylight exposure. Efficacy at 3 months was assessed clinically and histologically. RESULTS: BF-200 ALA cleared 71/84 (84·5%) and MAL 69/93 (74·2%) of the AKs (P = 0·099), all grades responding equally, but with new AKs appearing during follow-up (n = 4, BF-200 ALA; n = 8, MAL). In per patient half-face analysis BF-200 ALA showed significantly higher clearance rates for grade I AKs than did MAL (P = 0·027), but for thicker grades, clearance was equal (P = 0·564). BF-200 ALA and MAL treatments resulted in 61·5% and 38·5% complete histological clearance (P = 0·375), respectively. p53 expression decreased by 54·4% and 33·7%, respectively (P = 0·552). Both treatments were nearly painless with similar adverse reactions and no difference in patient preference. CONCLUSIONS: BF-200 ALA showed a trend towards improved efficacy results compared with MAL. Thicker lesions in both groups responded when treated repeatedly. Importantly, a thin 0·25-mm layer of the photosensitizer precursors was sufficient, which may lead to lower expense.

Long-term renal function following bone marrow transplantation.

Renal function, evaluated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), was investigated in 187 pediatric patients who underwent allogeneic (n=169) or autologous bone marrow transplantation (BMT). Allogeneic BMT patients were divided into three groups: hematological malignancies, aplastic anemia and non-malignant diseases, whereas autologous patients constituted a fourth group. A total of 64% received total body irradiation (TBI) as conditioning therapy, and 50 healthy children served as controls. GFR and ERPF were normal before transplantation. After 1 year, both GFR and ERPF were significantly reduced. GFR had recovered slightly after 3 years and remained stable thereafter. Recovery in ERPF was not apparent. Renal impairment was found in 41% of patients at 1 year, in 31% at 3 years and in 11% 7 years after BMT. Patients with hematological malignancies had lower GFRs than patients with non-malignant diseases at all time points. The most important risk factor as regards chronic renal impairment was TBI. Type of donor, cyclophosphamide (CY), or acute graft-versus-host disease (GVHD) did not seem to contribute to the development of chronic renal impairment. We suggest that tests of renal function should be included in long-term followup after BMT.

Screening for endometrial cancer in asymptomatic postmenopausal women with conventional and colour Doppler sonography.

OBJECTIVE: To evaluate endometrial thickness and uterine arterial flow measurement as predictors of endometrial cancer. DESIGN: Prospective study among a cohort of women invited to age-adjusted, population-based breast cancer screening by mammography. SETTING: City of Turku, Finland. POPULATION: 1074 postmenopausal women aged 57-61 years (mean 59 years). METHODS: Conventional and colour Doppler sonography. Endometrial biopsy was taken when the endometrial thickness (double layer) was > or = 4.0 mm, if the uterine artery pulsatility index was < or = 1.0 or if there was a fluid accumulation in the endometrial cavity. MAIN OUTCOME MEASURES: Detection of endometrial cancer in endometrial biopsy. Record linkage with the files of the Finnish Cancer Registry three and a half years after the first ultrasound examination. Major statistical results are based on the analysis of variance and logistic regression models. RESULTS: An endometrial biopsy was taken from 291 women (27%). One woman had endometrial tuberculosis, three an endometrial polyp, 16 endometrial hyperplasia, three endometrial carcinoma (Stage Ib), and one had cervical carcinoma (Stage Ib). One woman was diagnosed as having endometrial cancer Stage Ib two and a half years after screening; she had refused further examination after a positive screen. A second endometrial cancer (Stage Ib) was diagnosed three years after a negative screening result. CONCLUSION: Transvaginal sonography is confirmed to have a very high sensitivity for the detection of early endometrial carcinoma, but the specificity remains low. If endometrial cancer is to be detected at an early stage, further examinations should be carried out when the endometrial thickness is > or = 4.0 mm, especially when the woman has risk factors such as obesity, late menopause or current use of hormonal replacement therapy. Doppler sonography does not improve the detection of premalignant and malignant endometrial lesions compared with normal ultrasound.

Altered skin sensitivity in chronic itch: role of peripheral and central mechanisms.

Nodular prurigo (NP) is a chronic skin disease causing severe itch of unknown origin in restricted skin areas surrounded by healthy skin areas. In the present investigation we studied cutaneous sensibility in five NP-patients and in five control subjects. Pain thresholds were determined with short argon laser pulses using two different sizes of stimulus surface (diameters 2 and 4 mm), tactile threshold with calibrated monofilaments and skin blood flow with a laser Doppler flowmeter. We also studied the effect of prolonged capsaicin treatment which should predominantly impair the function of nociceptive C-fibers. In both the itching and healthy skin areas the pain thresholds were lower in NP-patients than in healthy control subjects. Before capsaicin, an increase in stimulus area produced an equal decrease in pain threshold in all subjects. Following prolonged capsaicin treatment the pain threshold obtained with a large but not a small stimulus surface was elevated to control levels in NP-patients. Tactile thresholds in NP-patients were lower than in control subjects, and this abnormality was reversed by capsaicin. The basal skin blood flow level was more labile (fluctuating) in itching skin areas than in healthy skin areas of NP-patients. Capsaicin reduced blood flow fluctuation in the itching area. A lowered pain threshold not only in the itching area but also in the healthy skin area of NP-patients suggests that central convergence of itch and pain may contribute to increased pain sensitivity in chronic itch. Capsaicin-reversible abnormal fluctuation of the blood flow in the itching skin area might be explained by abnormal spontaneous activity of nociceptive peripheral nerve fibers and a consequent release of vasoactive agents from their terminals (axon reflex). The decreased tactile threshold and the elevation of it by capsaicin indicates that also the mechanisms underlying tactile sensibility are changed in chronic itch patients.

Endometrial fluid accumulation in asymptomatic postmenopausal women.

Postmenopausal endometrial fluid accumulation was considered in the past to be related to cancer of the genital organs. Our purpose was to evaluate its prevalence, and its association with cervical stricture, use of hormone replacement therapy and endometrial pathology. A group of 1074 asymptomatic postmenopausal women aged 57-61 (mean 59) years was examined by transvaginal sonography with color Doppler imaging. Women who had an endometrial fluid accumulation underwent endometrial biopsy. Statistical analysis was mainly based on analysis of variance. Endometrial fluid accumulation was found in 134 women (12%). Women using only estrogen as hormone replacement therapy had a relative risk of 3.5 of endometrial fluid accumulation. In 12 women (9%), a cervical stricture precluded endometrial sampling. Six abnormal histopathological samples were found (5%): two endometrial polyps, one cystic hyperplasia, two adenomatous hyperplasias but only one adenocarcinoma. One further patient with endometrial cancer was registered by the Finnish Cancer Registry 2.5 years later in a woman who had refused endometrial sampling. Endometrial fluid accumulation is quite a common finding on transvaginal sonography among asymptomatic postmenopausal women and the process may be multifactorial. Cervical stricture is not the most important etiological factor. The use of estrogen replacement therapy increases the risk of endometrial fluid accumulation; however, it is rarely a sign of malignancy.

Influence of selective nerve fiber blocks on argon laser-induced thermal pain in the human skin.

Influence of selective nerve fiber blocks on cutaneous pain induced by short argon laser pulses was studied in healthy humans. The minimal energy per surface area needed to produce a pain sensation was lower with a larger stimulus surface indicating spatial summation. Both compression of the peripheral nerve innervating the stimulus site (A-fiber block) and prolonged topical treatment of the stimulus site with 1% capsaicin (a predominant block of nociceptive C-fibers) produced an elevation of the pain threshold. Prolonged capsaicin treatment produced significantly higher pain thresholds than the compression block. Magnitude of the pain threshold elevation induced by nerve blocks varied depending on the area of the stimulus surface. Especially following prolonged capsaicin treatment, pain threshold elevations tended to be smaller with the larger area of the stimulus surface suggesting an enhanced spatial summation effect. Tactile thresholds were significantly elevated only by the compression block. The results indicate that nociceptive C-fibers have a significant contribution to the threshold sensation of pain induced by argon laser. Moreover, following impairment of function in nociceptive C-fibers, the spatial summation of argon laser-induced pain tends to be enhanced.

Transdermal estrogen for female stress urinary incontinence in postmenopause.

OBJECTIVE: To evaluate the effect of transdermal estrogen for stress urinary incontinence in postmenopause. STUDY DESIGN: An open within patient, dose-finding study with transdermal 17-beta-estradiol combined with cyclic medroxyprogesterone acetate was conducted over 9 months in 21 patients (mean age 57.3 years) suffering from urodynamically verified mild to moderate stress incontinence without detrusor instability. RESULTS: Subjective improvement was noted in 16 out of 21 patients (76%). The dose level of 50 micrograms was better tolerated than 100 micrograms and sufficient enough to achieve continence. CONCLUSION: Transdermal estrogen therapy plays an adjuvant role in conservative therapy for mild to moderate stress urinary incontinence in postmenopausal women.

An attempt to attenuate experimental pain in humans by dextromethorphan, an NMDA receptor antagonist.

Dextromethorphan (100 mg, orally), an NMDA receptor antagonist, did not significantly attenuate pain intensity or unpleasantness induced by experimental ischemia or by topical capsaicin in healthy human subjects, nor did it increase the threshold for heat pain or mechanical pain. A dose of 200 mg produced marked side effects. Thus, systemically administered dextromethorphan does not attenuate pain at clinically applicable doses in humans.

Evaluation of ovarian findings in asymptomatic postmenopausal women with color Doppler ultrasound.

BACKGROUND: To evaluate the prevalence and significance of abnormal ovarian findings in asymptomatic postmenopausal women, screening for ovarian cancer with color Doppler ultrasound was performed. METHODS: One thousand three hundred sixty-four asymptomatic women aged 56-61 years (mean, 59 years) were examined by color Doppler sonography. Ninety-six percent of the examinations were transvaginal and 4% transabdominal. The criteria for abnormality were an ovarian volume 8 cm3 or greater, nonuniform echogenicity, and/or pulsatility index (PI) of the ovarian artery or tumor vessel, if present, 1.0 or less. Repeat sonograms were performed 1-3 months later on all patients with abnormal findings, and exploratory laparotomy was performed if a malignant tumor was suspected. RESULTS: Abnormal ovarian findings were detected in 160 women (12%). At the time of repeat sonogram there were 28 persisting abnormalities (2%). At that time, the ovary was regarded as normal if it still contained a small clear cyst with an unchanged greatest dimension of less than 20 mm. Three women had a low PI value but all had also abnormal ovarian sonographic morphology. Two ultrasound-guided cyst punctures were performed and three patients had surgery; one benign serous cyst, one benign serous cystadenoma, and one serous cystadenoma of borderline malignancy were detected. The remaining abnormal findings disappeared or remained unchanged during a minimum follow-up of 2 years. One case of Stage IA ovarian cancer has been reported 2 years after a negative screening and one abdominal carcinomatosis 2 1/2 years after a negative screening result. CONCLUSIONS: There is a high frequency of small ovarian cysts in asymptomatic postmenopausal women. A large percentage of these cysts regress spontaneously or remain unchanged. Transvaginal color Doppler ultrasound is an effective method for detecting these lesions. Color Doppler does not increase substantially the number of operations for benign reasons. However, as a primary screening modality, the conventional sonography seems to be quite sufficient.

Effect of cocaine on sexual behaviour in male stumptail macaques (Macaca arctoides).

The effect of cocaine (0.01-1.0 mg/kg) on sexual behaviour was studied in four male stumptail macaques (Macaca arctoides). Following drug-saline control administration, the behaviour of the male monkey with a female was observed for 30 min in two different behavioural conditions; in one of the conditions the baseline sexual activity was low, and in the other it was high (partial or complete separation of the male and the female between the sessions, respectively). The reversal of the cocaine-induced effects was attempted by haloperidol (0.003-0.01 mg/kg), a dopamine-2-receptor antagonist. Cocaine (0.1-1.0 mg/kg) produced a highly significant dose-dependent suppression in the number of ejaculations. The cocaine-induced suppression of ejaculatory behaviour was completely reversed by haloperidol. Haloperidol at the dose range used did not in itself influence ejaculatory behaviour. The effect of cocaine on grooming, nonejaculatory mounting, aggression, or perineal investigations did not reach statistical significance. The possibility that cocaine at very low doses (0.01-0.1 mg/kg) might increase sexual activity was excluded in the behavioural condition with a low basal sexual activity. The results indicate that cocaine dose-dependently suppresses ejaculatory behaviour as a result of dopamine-2-receptor-mediated mechanisms. The cocaine-induced suppression of ejaculatory behaviour might be explained by the strong rewarding effect of cocaine alone.

A longitudinal study of screening for endometrial cancer by endometrial biopsy in diabetic females.

Diabetics are at high risk of developing endometrial cancer; the relative risk of endometrial cancer in diabetics is fourfold in comparison to non-diabetic controls. The purpose of this longitudinal study was to evaluate the effectiveness of screening asymptomatic diabetic females in terms of the premalignant and malignant endometrial findings, and to try to determine the optimal screening interval. In 1980-1981, a group of 462 diabetic females was identified and registered. One half of them (237) was invited to be screened. Endometrial samples were taken by using Vabra aspiration. The results of this first randomized screening in 1980-1981 have been published elsewhere. At that time 124 females participated. The remaining 225 females acted as an unscreened control group. Eight years later (1988-1989), both groups were invited to be screened. The Pistolet aspiration method was used. At this stage, group 1 (screened in 1980-1981) consisted of 78 females, and group 2 (not screened in 1980-1981) consisted of 148 females. In 85% (193/226) of the females, the uterine cavity was reached with the Pistolet instrument; 96% of the females found the pain acceptable. In the group screened twice (group 1), no pathologic lesions of the endometrium were found in the second screening. In the group screened for the first time (group 2), one female had endometrial adenocarcinoma (0.8%), one had complex hyperplasia without atypia (0.8%) and four had endometrial polyps (3.3%). In 165 cases of 193, both a cytologic and a histologic specimen were available. In 130 cases (79%) the cytology was of class I, including the one endometrial adenocarcinoma. In three cases (2%) it was of class II and in one case (1%) of class III. Endometrial biopsy by Pistolet aspiration was a method highly acceptable by the patients for examining the endometrium. However, cytologic examination was not able to show the existing endometrial adenocarcinoma. One endometrial sampling of asymptomatic diabetic females during early menopause could detect the bulk of the occult, slowly progressing lesions of the endometrium. Such screeening might be most efficient in terms of cost-benefit ratio.

Capsaicin-induced central facilitation of a sympathetic vasoconstrictor response to painful stimulation in humans.

The effect of capsaicin, a compound selectively activating nociceptive primary afferent fibers, on a centrally mediated autonomic (sympathetic) vasoconstriction response to painful peripheral stimulation was studied in healthy human volunteers. Capsaicin (1%) was applied topically to the dorsal forearm and the threshold for eliciting a vasoconstriction response in the contralateral forefinger to painful electrical or thermal stimulation of the forearm skin adjacent to or remote from the capsaicin-treated region was determined with Laser Doppler flowmetry. Capsaicin produced a significant decrease of the threshold for the vasoconstriction response to painful electrical stimulation of the area of central allodynia; i.e., the skin area located adjacent to the capsaicin-treated region in which a light touch evoked an unpleasant sensation. Capsaicin did not change the threshold for the vasoconstriction response to painful heat stimuli applied to the area of central allodynia or to painful electric stimulation applied outside the borders of the allodynic area. Heart rate, blood pressure and heart vagal tone were not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central submodality-dependent facilitation of an autonomic vasoconstriction response to noxious stimulation in humans. This central facilitation can be explained by segmental excitability changes of afferent interneurons at the spinal cord level.