PubMed Health⌕ Search

Biomedical subjects

R Baron

Publications and source records attributed to R Baron.

At least 91 records · Page 5Linked to original sources
PubMed2000

No effect of sympathetic sudomotor activity on capsaicin-evoked ongoing pain and hyperalgesia.

BACKGROUND: Complex regional pain syndromes (causalgia and RSD) can be relieved by blockade of the sympathetic efferent activity. The mechanisms of sympathetically maintained pain (SMP) are unclear. So far an adrenergic interaction between sympathetic vasoconstrictor neurons and nociceptors has been proposed. Alternatively, a cholinergic coupling of sympathetic sudomotor neurons and nociceptors is possible. OBJECTIVE: To determine the effect of cutaneous sympathetic sudomotor activity on pain induced by primary afferent C-nociceptor activation with capsaicin in humans. METHODS: In 10 healthy volunteers capsaicin was injected into the forearm skin to induce ongoing pain and dynamic and punctate mechanical hyperalgesia. Intensity of pain and hyperalgesia and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of low and high sympathetic sudomotor skin activity induced by whole-body temperature changes with a thermal suit. By altering whole-body temperature from a moderately warm to an intensely warm state, sympathetic sudomotor activity is modulated selectively in the widest range that can be achieved physiologically while sympathetic vasoconstrictor activity is continuously inhibited. The degree of sudomotor discharge was monitored by measuring cutaneous sweat production at the forearm with the colour indicator ponso-red. The inhibition of vasocontrictor discharge was monitored by measuring cutaneous blood flow at the index finger with laser Doppler flowmetry. RESULTS: The intensity and spatial distribution of capsaicin-evoked ongoing pain and dynamic and punctate mechanical hyperalgesia were not significantly different during the presence of high and low sympathetic sudomotor discharge. CONCLUSIONS: Cutaneous sympathetic sudomotor activity does not influence capsaicin induced pain and mechanical hyperalgesia.

Adult↗
PubMed2000

An antisense oligonucleotide targeting the alphaV integrin gene inhibits adhesion and induces apoptosis in breast cancer cells.

The aim of this study was to show the anti-adhesive potential of an antisense oligodeoxynucleotide (ODN) approach when designed to suppress the cellular function of the alphaV integrin subunit in breast cancer cells. The alphaV integrins play major roles in favouring breast cancer spreading. In this study, we inhibited alphaV subunit synthesis in the human breast carcinoma cell line, MDA-MB231, by a partially phosphorothioated antisense oligodeoxynucleotide (5543-ODN). The alphaV antisense 5543-ODN reduced alphaV, but not actin, mRNA transcription and protein expression by 55% and 65% respectively (1 microM, 72 h). Control sense and mismatch reagents were inactive. The antisense, but not the sense and mismatch, 5543-ODN induced dose- and time-dependent inhibition of MDA-MB231 adhesion to serum, vitronectin, fibrinogen and fibronectin substrates but was inactive on adhesion to laminin. Thus, the alphaV integrin was located in adhesion structures, which were disrupted by treatment with the alphaV antisense 5543-ODN. Antisense treated cells also showed evidence of programmed cell death with the appearance of apoptotic bodies. MDA-MB231 cells express a mutant form of the pro-apoptotic factor p53; however, no changes in the expression of p53 were observed by Western blotting. Immunofluorescence did reveal an increased nuclear translocation of p53 suggesting activation of the protein, but such a translocation did not lead to significant changes in either the expression of the cyclin dependent kinase inhibitor, p21(WAF1/CIP1) the cell survival factor Bcl-2 or the pro-apoptotic factor Bax.

Antigens, CD↗
PubMed2000

A Src SH2 selective binding compound inhibits osteoclast-mediated resorption.

BACKGROUND: The observations that Src(-/-) mice develop osteopetrosis and Src family tyrosine kinase inhibitors decrease osteoclast-mediated resorption of bone have implicated Src in the regulation of osteoclast-resorptive activity. We have designed and synthesized a compound, AP22161, that binds selectively to the Src SH2 domain and demonstrated that it inhibits Src-dependent cellular activity and inhibits osteoclast-mediated resorption. RESULTS: AP22161 was designed to bind selectively to the Src SH2 domain by targeting a cysteine residue within the highly conserved phosphotyrosine-binding pocket. AP22161 was tested in vitro for binding to SH2 domains and was found to bind selectively and with high affinity to the Src SH2 domain. AP22161 was further tested in mechanism-based cellular assays and found to block Src SH2 binding to peptide ligands, inhibit Src-dependent cellular activity and diminish osteoclast resorptive activity. CONCLUSIONS: These results indicate that a compound that selectively inhibits Src SH2 binding can be used to inhibit osteoclast resorption. Furthermore, AP22161 has the potential to be further developed for treating osteoporosis.

Amino Acid Sequence↗
PubMed2000

Progressive increase in bone mass and development of odontomas in aging osteopetrotic c-src-deficient mice.

The critical role of c-src in osteoclast-mediated bone resorption has been emphasized by gene deletion experiments in mice. However, the long-term effects of the lack of c-src and impaired osteoclast function on the skeleton remain unknown. To further study the physiological role of c-src and to circumvent the early death of src(-/-) mice, due to starvation in the absence of erupted teeth, we maintained mice on a liquid diet. At the age of 2 months the src(-/-) mice presented signs of airway obstruction and all mice died progressively between 2.5 and 6 months of age. Radiography demonstrated severe osteopetrosis of the whole skeleton. Histomorphometrical analysis of the src(-/-) mice confirmed a significant increase in bone mass with age, resulting in complete loss of bone marrow spaces in some bones and explaining the consistent hepatosplenomegaly, due to extraskeletal hematopoesis. Histopathological examination of the skull revealed the presence of odontomas in the region of the unerupted incisors, with a penetrance of 100% in the aging src(-/-) mice. Although odontomas are benign lesions, their progressive growth leads to the obliteration of the nasal airways, progressive suffocation, and death in src(-/-) mice. These results suggest that: (i) in the absence of bone resorption, bone formation continues and leads to progressive accentuation of the osteopetrotic phenotype in src(-/-) mice; (ii) osteoclastic function is required for regular eruption of the incisors and deficient bone resorption is associated with the development of odontomas; and (iii) src(-/-) mice die by suffocation due to airway obliteration as a result of progressive odontoma growth.

Aging↗
PubMed2000

Overexpression of DeltaFosB transcription factor(s) increases bone formation and inhibits adipogenesis.

Members of the AP-1 family of transcription factors participate in the regulation of bone cell proliferation and differentiation. We report here a potent AP-1-related regulator of osteoblast function: DeltaFosB, a naturally occurring truncated form of FosB that arises from alternative splicing of the fosB transcript and is expressed in osteoblasts. Overexpression of DeltaFosB in transgenic mice leads to increased bone formation throughout the skeleton and a continuous post-developmental increase in bone mass, leading to osteosclerosis. In contrast, DeltaFosB inhibits adipogenesis both in vivo and in vitro, and downregulates the expression of early markers of adipocyte differentiation. Because osteoblasts and adipocytes are thought to share a common precursor, it is concluded that DeltaFosB transcriptionally regulates osteoblastogenesis, possibly at the expense of adipogenesis.

Adipocytes↗
PubMed2000

Comparison of laboratory and "on-court" endurance testing in tennis.

Treadmill testing (TT) commonly used in endurance testing is often not sport-specific. Therefore a field test (FT) for tennis players was developed. The purpose was 1) to compare metabolic and cardiorespiratory response between TT and FT and 2) to assess tennis stroke ratings during FT. In both tests ventilatory variables (VO2, VE, VT, Bf, VE x VO2(-1)), heart rate (HR), and lactate (LA) were measured. For both tests an "individual anaerobic threshold" (IAT) was calculated. The comparison of TT and FT yielded significant differences in cardiorespiratory and metabolic response. LA and VE were significantly higher in TT compared to FT at VO2 of 35, 40, and 45 ml x kg(-1) x min(-1). There were statistical differences between IAT resulting from both tests (TT vs. FT): HR (165+/-16, 175+/-11, p<0.001), VO2 (44.4+/-4.3, 47.8+/-4.8, p<0.05), LA (3.1+/-0.5, 2.5+/-0.4, p < 0.001), VE (97.0+/-15.6, 89.1+/-14.9, p < 0.05), VT (2.66+/-0.34, 2.34+/-0.47, p<0.05), VE/VO2 (27.9+/-3.9, 23.9+/-2.9, p<0.01). High correlation was found between stroke ratings and the national ranking of the players. We concluded that 1) metabolic, ventilatory, and cardiorespiratory demands of TT vs. FT were (semi)sport-specific and significantly different and 2) that the stroke rating in our study was a good predictor for tournament performance (r = 0.94). This type of stroke rating can be implemented in a FT.

Adult↗
PubMed2000

Peripheral neuropathic pain: from mechanisms to symptoms.

Several independent pathophysiological mechanisms in both the peripheral and central nervous system are responsible for sensory symptoms as well as spontaneous and evoked pains in peripheral neuropathies: (1) Pathologic active or sensitized nociceptors can induce secondary changes in central processing, leading to spinal cord hyperexcitability that causes input from mechanoreceptive Abeta-fibers (light touching) to be perceived as pain. These patients characteristically have spontaneous pain, heat hyperalgesia, static mechanical allodynia, and and severe dynamic mechanical allodynia. (2) Nociceptor function may be selectively impaired within the allodynic skin. Pain and temperature sensation are profoundly impaired but light moving mechanical stimuli can often produce severe pain (dynamic mechanical allodynia). Anatomic reorganization in the dorsal horn resulting from C-fiber degeneration may lead to Abeta-fiber-mediated allodynia. (3) Persistent inflammatory reactions of the nerve trunk can induce ectopic activity in primary afferent nociceptors and thus is a potential cause of spontaneous pain and allodynia. This effect is mediated by the cytokine tumor necrosis factor-alpha produced by activated macrophages. (4) After nerve lesion the sympathetic nervous system might interact with afferent neurons. Activity in sympathetic fibers can induce further activity in sensitized nociceptors and, therefore, enhance pain and allodynia (sympathetically maintained pain). This pathologic interaction acts via noradrenaline released from sympathetic terminals and newly expressed receptors on the afferent neuron membrane. These mechanisms can operate in concert in a single disease entity (e.g., postherpetic neuralgia) and also in a single patient. Distinct pathophysiological mechanisms lead to specific sensory symptoms (e.g., dynamic mechanical allodynia, cold hyperalgesia). It is also possible that the pain-generating mechanism and the symptoms change during the course of the disease. A thorough analysis of sensory symptoms may, reveal the underlying mechanisms that are mainly active in a particular patient. The treatment of neuropathic pain is currently unsatisfactory. In the future, drugs will be developed that address specifically the relevant combination of mechanisms.

Animals↗
PubMed2000

Change in left atrial and ventricular dimensions during and immediately after exercise.

PURPOSE: The aim of this study was to evaluate differences in the left atrial (LAD), total ventricular end-diastolic (TEDD), end-systolic diameters (TESD), and left ventricular shortening fraction (SF) compared with heart rate (HR) and systolic blood pressure (SBP) during exercise and recovery. METHODS: Healthy young male (N = 15) and female (N = 16) subjects performed an incremental cycle ergometer test in upright position, and three phases of energy supply were defined by means of blood lactate concentration (LA) and respiratory gas exchange variables (I: aerobic; II: aerobic-anaerobic transition; III: anaerobic). Subjects were required to rest their arms on a steering bar and to lean their upper body forward; two dimensional (2-D) echocardiograms were obtained over the left parasternal area at rest (R), at the end of each phase, immediately within 15 s post, and 6 min after exercise (6 min). By using VINGMED's "Anatomical M-Mode," it was possible to extract M-Mode Sweeps from stored 2-D-Loops and perform the M-Mode measurement. RESULTS: In contrast to the significant decrease in TEDD and TESD from III to 15 s up to resting values and the significant increase in SF from III to 15 s, the moderate decrease in HR immediately post exercise (15 s) was not significant. The SBP showed a significantly decrease from III to 15 s; in contrast to TEDD, TESD, and SF, the values at 15 s were comparable with the values at II. For LAD, significant increase during exercise and a decrease during recovery were observed. Sex-specific differences of changes in measured variables could not be found. CONCLUSION: We concluded that post exercise measurement of left ventricular and atrial dimensions or SF were not valid to describe heart function at maximal exercise although immediately post exercise HR was near maximal level.

Adult↗
PubMed2000

Cross-sectional survey of trachoma in school age children in the region of Thiès (Senegal).

BACKGROUND: Trachoma is a leading cause of blindness in West Africa. In Senegal previous studies have shown that the endemicity is high. AIMS: To verify the extent of the pathology and to study the epidemiologic characters of this infectious disease in a population of school age children in a rural zone, located in the Thiès region (Senegal). METHODS: A cross-sectional survey in six villages in the region of Thiès was performed in a population of school age children (5 to 15 years old). Sixty variables (individual, family, village, etc.) with morbidity indicators for trachoma cases were collected and analyzed. RESULTS: The cross-sectional survey confirmed the extent of the prevalence of trachoma in the childhood population; 208 of the 388 children (mean age, 9.19 years) included had trachoma (53.6%). Significant statistical correlations were found among the occurrence of trachoma and ethnic origins, the village of residence, the father's profession and the daily quantity of water ingested and its origin. Inversely no correlation could be found between the occurrence of trachoma and sex, age (except for florid trachoma), the size of the sibship, whether the mother washes the child, washing their hands before eating, the number of cospouses and the number of children per mother. CONCLUSIONS: The data obtained confirmed the extent of this endemic disease in the region of Thiès, because dispensing antibiotic eye drop has limited efficacy over time. Information should be provided to the population on the extent of the disease and its epidemiologic characteristics and more widespread well drilling, and use of that water should be encouraged.

Adolescent↗
PubMed2000

Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5.

Growth hormone (GH) regulates both bone growth and remodeling, but it is unclear whether these actions are mediated directly by the GH receptor (GHR) and/or IGF-I signaling. The actions of GH are transduced by the Jak/Stat signaling pathway via Stat5, which is thought to regulate IGF-I expression. To determine the respective roles of GHR and IGF-I in bone growth and remodeling, we examined bones of wild-type, GHR knockout (GHR(-/-)), Stat5ab(-/-), and GHR(-/-) mice treated with IGF-I. Reduced bone growth in GHR(-/-) mice, due to a premature reduction in chondrocyte proliferation and cortical bone growth, was detected after 2 weeks of age. Additionally, although trabecular bone volume was unchanged, bone turnover was significantly reduced in GHR(-/-) mice, indicating GH involvement in the high bone-turnover level during growth. IGF-I treatment almost completely rescued all effects of the GHR(-/-) on both bone growth and remodeling, supporting a direct effect of IGF-I on both osteoblasts and chondrocytes. Whereas bone length was reduced in Stat5ab(-/-) mice, there was no reduction in trabecular bone remodeling or growth-plate width as observed in GHR(-/-) mice, indicating that the effects of GH in bone may not involve Stat5 activation.

Animals↗
PubMed2000

Osteopenia and decreased bone formation in osteonectin-deficient mice.

Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled synthesis and resorption of collagenous and noncollagenous extracellular matrix proteins, and an imbalance in this process can lead to disease states such as osteoporosis, or more rarely, osteopetrosis. There is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling. Osteonectin is abundant in bone and is expressed in areas of active remodeling outside the skeleton. In vitro studies indicate that osteonectin can bind collagen and regulate angiogenesis, metalloproteinase expression, cell proliferation, and cell-matrix interactions. In some osteopenic states, such as osteogenesis imperfecta and selected animal models for bone fragility, osteonectin expression is decreased. To determine the function of osteonectin in bone, we used contact x-ray, histomorphometry, and Northern blot analysis to characterize the skeletal phenotype of osteonectin-null mice. We found that osteonectin-null mice have decreased bone formation and decreased osteoblast and osteoclast surface and number, leading to decreased bone remodeling with a negative bone balance and causing profound osteopenia. These data indicate that osteonectin supports bone remodeling and the maintenance of bone mass in vertebrates.

Animals↗
PubMed1999

Ligand-induced ubiquitination of the epidermal growth factor receptor involves the interaction of the c-Cbl RING finger and UbcH7.

c-Cbl plays a negative regulatory role in tyrosine kinase signaling by an as yet undefined mechanism. We demonstrate here, using the yeast two-hybrid system and an in vitro binding assay, that the c-Cbl RING finger domain interacts with UbcH7, a ubiquitin-conjugating enzyme (E2). UbcH7 interacted with the wild-type c-Cbl RING finger domain but not with a RING finger domain that lacks the amino acids that are deleted in 70Z-Cbl, an oncogenic mutant of c-Cbl. The in vitro interaction was enhanced by sequences on both the N- and C-terminal sides of the RING finger. In vivo and in vitro experiments revealed that c-Cbl and UbcH7 synergistically promote the ligand-induced ubiquitination of the epidermal growth factor receptor (EGFR). In contrast, 70Z-Cbl markedly reduced the ligand-induced, UbcH7-mediated ubiquitination of the EGFR. MG132, a proteasome inhibitor, significantly prolonged the ligand-induced phosphorylation of both the EGFR and c-Cbl. Thus, c-Cbl plays an essential role in the ligand-induced ubiquitination of the EGFR by a mechanism that involves an interaction of the RING finger domain with UbcH7. This mechanism participates in the down-regulation of tyrosine kinase receptors and loss of this function, as occurs in the naturally occurring 70Z-Cbl isoform, probably contributes to oncogenic transformation.

Cysteine Endopeptidases↗
PubMed1999

Leucine zipper-mediated homodimerization of the adaptor protein c-Cbl. A role in c-Cbl's tyrosine phosphorylation and its association with epidermal growth factor receptor.

The 120-kDa proto-oncogenic protein c-Cbl is a multidomain adaptor protein that is phosphorylated in response to the stimulation of a broad range of cell surface receptors and participates in the assembly of signaling complexes that are formed as a result of the activation of various signal transduction pathways. Several structural features of c-Cbl, including the phosphotyrosine-binding domain, proline-rich domain, and motifs containing phosphotyrosine and phosphoserine residues, mediate the association of c-Cbl with other components of these complexes. In addition to those domains that have been demonstrated to play a role in the binding of c-Cbl to other signaling molecules, c-Cbl also contains a RING finger motif and a putative leucine zipper. In this study, we demonstrate that the previously identified putative leucine zipper mediates the formation of Cbl homodimers. Using the yeast two-hybrid system, we show that deletion of the leucine zipper domain is sufficient to abolish Cbl homodimerization, while Cbl mutants carrying extensive N-terminal truncations retain the ability to dimerize with the full-length Cbl. The requirement of the leucine zipper for the homodimerization of Cbl was confirmed by in vitro binding assays, using deletion variants of the C-terminal half of Cbl with and without the leucine zipper domain, and in cells using Myc and green fluorescent protein (GFP) N-terminal-tagged Cbl variants. In cells, the deletion of the leucine zipper caused a decrease in both the tyrosine phosphorylation of Cbl and its association with the epidermal growth factor receptor following stimulation with epidermal growth factor, thus demonstrating a role for the leucine zipper in c-Cbl's signaling functions. Thus, the leucine zipper domain enables c-Cbl to homodimerize, and homodimerization influences Cbl's signaling function, modulating the activity of Cbl itself and/or affecting Cbl's associations with other signaling proteins in the cell.

Cell Line↗
PubMed1999

Cytoskeleton-dependent tyrosine phosphorylation of the p130(Cas) family member HEF1 downstream of the G protein-coupled calcitonin receptor. Calcitonin induces the association of HEF1, paxillin, and focal adhesion kinase.

HEF1 is a recently described p130(Cas)-like docking protein that contains one SH3 domain and multiple SH2 binding motifs. In B cells, HEF1 is phosphorylated by a cytoskeleton-dependent mechanism that is triggered by integrin ligation. However, the induction of HEF1 phosphorylation by G protein-coupled receptors has not been reported. We found that HEF1, but not p130(Cas), is tyrosine-phosphorylated following stimulation of the rabbit C1a calcitonin receptor stably expressed in HEK-293 cells. The calcitonin-induced tyrosine phosphorylation of HEF1 increased in a time- and dose-dependent manner. Dibutyryl cAMP and forskolin had little or no effect on HEF1 phosphorylation, and the protein kinase A inhibitor H89 failed to detectably inhibit the response to calcitonin, indicating that the G(s)/cAMP/protein kinase A pathway does not mediate the calcitonin effect. Pertussis toxin, which selectively blocks G(i/o) signaling, also had no effect. Increasing cytosolic Ca(2+) with ionomycin stimulated HEF1 phosphorylation and preventing any calcitonin-induced change in cytosolic calcium by a combination of BAPTA and extracellular EGTA completely blocked the calcitonin-induced tyrosine phosphorylation of HEF1. Phorbol 12-myristate 13-acetate also induced HEF1 tyrosine phosphorylation, and the protein kinase C inhibitor calphostin C completely inhibited both calcitonin- and phorbol 12-myristate 13-acetate-stimulated HEF1 phosphorylation. Calcitonin also induced the tyrosine phosphorylation of paxillin and focal adhesion kinase, and the association of these two proteins with HEF1. Pretreatment with cytochalasin D, which disrupts actin microfilaments, prevented the calcitonin-induced HEF1 and paxillin phosphorylation. In conclusion, the calcitonin-stimulated tyrosine phosphorylation of HEF1 is mediated by calcium- and protein kinase C-dependent mechanisms and requires the integrity of the actin cytoskeleton.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Brain processing of capsaicin-induced secondary hyperalgesia: a functional MRI study.

OBJECTIVE: To investigate, using functional MRI (fMRI), the neural network that is activated by the pain component of capsaicin-induced secondary mechanical hyperalgesia. BACKGROUND: Mechanical hyperalgesia (i.e., pain to innocuous tactile stimuli) is a distressing symptom of neuropathic pain syndromes. Animal experiments suggest that alterations in central pain processing occur that render tactile stimuli capable of activating central pain-signaling neurons. A similar central sensitization can be produced experimentally with capsaicin. METHODS: In nine healthy individuals the cerebral activation pattern resulting from cutaneous nonpainful mechanical stimulation at the dominant forearm was imaged using fMRI. Capsaicin was injected adjacent to the stimulation site to induce secondary mechanical hyperalgesia. The identical mechanical stimulation was then perceived as painful without changing the stimulus intensity and location. Both activation patterns were compared to isolate the specific pain-related component of mechanical hyperalgesia from the tactile component. RESULTS: The pattern during nonpainful mechanical stimulation included contralateral primary sensory cortex (SI) and bilateral secondary sensory cortex (SII) activity. During hyperalgesia, significantly higher activation was found in the contralateral prefrontal cortex: the middle (Brodmann areas [BAs] 6, 8, and 9) and inferior frontal gyrus (BAs 44 and 45). No change was present within SI, SII, and the anterior cingulate cortex. CONCLUSIONS: Prefrontal activation is interpreted as a consequence of attention, cognitive evaluation, and planning of motor behavior in response to pain. The lack of activation of the anterior cingulate contrasts with physiologic pain after C-nociceptor stimulation. It might indicate differences in the processing of hyperalgesia and C-nociceptor pain or it might be due to habituation of affective sensations during hyperalgesia compared with acute capsaicin pain.

Adult↗
PubMed1999

Effect of sympathetic activity on capsaicin-evoked pain, hyperalgesia, and vasodilatation.

BACKGROUND: Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. OBJECTIVE: To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. METHODS: In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. RESULTS: The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. CONCLUSIONS: Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.

Adult↗