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PubMed2005

Poststenotic flow and intracranial hemodynamics in patients with carotid stenosis: transoral carotid ultrasonography study.

BACKGROUND AND PURPOSE: In severe carotid stenosis, blood supply via the poststenotic internal carotid artery (ICA) and collateral pathways determine cerebral perfusion. We investigated whether poststenotic flow on transoral carotid ultrasonography (TOCU) is predictive of cerebral hemodynamics. METHODS: Eighty-eight patients with unilateral carotid stenosis underwent TOCU to analyze blood flow velocity and poststenotic diameter of the extracranial ICA. Intracranial collaterals and cerebral hemodynamics were assessed with selective angiography and single photon emission CT. RESULTS: Poststenotic diameter (P <.0001) and velocities (peak systolic velocity [PSV], time-averaged mean velocity [TMV], end-diastolic velocity [EDV]; all P < or = .009) decreased with stenotic severity. Poststenotic diameter was correlated with PSV (r=0.36, P=.0005), EDV (r=0.32, P=.002), and TMV (r=0.39, P=.0001). Poststenotic flow was significantly lower with collateral pathways than without pathways (P < or = .02) and significantly decreased as the number of the collaterals increased (P <.0001). Flow <5 mL/s indicated collaterals (81% sensitivity, 80% specificity). When flow was <5 mL/s, the asymmetry index in the middle cerebral artery (MCA) territory was significantly low during rest (P=.003) and after acetazolamide challenge (P=.006). Poststenotic flow velocity was associated with baseline (P=.007) and postacetazolamide (P=.0009) MCA asymmetry indexes. CONCLUSION: Poststenotic ICA flow measured with TOCU reflects collateral flow and cerebral hemodynamics in patients with severe carotid stenosis. This technique may provide new parameters for screening patients with hemodynamically significant carotid stenosis.

Acetazolamide↗
PubMed1989

Increased sensitivity to 1-beta-D-arabinofuranosylcytosine in P388 murine leukemic cells resistant to etoposide.

A variant P388 murine leukemic cell resistant to 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidine)-beta-D-gl ucopyranoside (etoposide) (VP-16-213) was cloned. The variant P388/VP-16 cell line was 159-fold resistant to VP-16. We found that this variant P388/VP-16 cell line showed collateral drug sensitivity to 1-beta-D-arabinofuranosylcytosine(Ara-C), determined by comparing the 50% inhibitory concentrations in 48-h growth inhibition assay. To clarify the mechanism of this increased sensitivity to Ara-C, we quantified the deoxyribonucleoside triphosphate pools and 1-beta-D-arabinofuranosylcytosine triphosphate(Ara-CTP) using high-performance liquid chromatography in the parent and drug-resistant sublines of P388 cells. The analysis of deoxyribonucleoside triphosphate pools revealed that the pyrimidine triphosphate pools were significantly decreased in the P388/VP-16 cell line and the Ara-CTP concentration of two variant cell lines were not significantly different. The Ara-CTP/dCTP ratio was significantly increased in P388/VP-16 cells. These data suggest that the inhibition of the dCTP de-novo pathway and the preservation of the dCTP salvage pathway in P388/VP-16 cells might correlate with the increased sensitivity to Ara-C.

Animals↗
PubMed1997

Impact of severity of coronary artery stenosis and the collateral circulation on the functional outcome of dyssynergic myocardium after revascularization in patients with healed myocardial infarction and chronic left ventricular dysfunction.

The aim of this study was to assess the influence of the severity of coronary artery stenosis and the grade of collateral circulation on myocardial viability in patients with chronic left ventricular (LV) dysfunction undergoing coronary artery bypass grafting. Forty patients (age 59 +/- 8 years) with old myocardial infarction were studied by dobutamine stress echocardiography (DSE) before coronary artery bypass grafting. LV function was assessed using a 16-segment, 5-grade score model. Viability and functional recovery were respectively defined as a reduction in wall motion score > or = 1 at low-dose DSE and at follow-up echocardiograms obtained 3 months after surgery. There were 56 stenotic coronary arteries subtending severely dyssynergic myocardial segments, of which 38 were occluded. Among 186 severely dyssynergic segments, functional recovery occurred in 42 (23%). There was no significant difference between myocordial regions with patent or occluded coronary arteries with respect to prevalence of viability or functional recovery and percentage of viable or recovered segments relative to the total number of dyssynergic segments. In patients with total occlusion, these parameters were not different between regions with different collateral grades. Sensitivity, specificity, and accuracy of low-dose DSE for prediction of regional functional recovery were 71%, 90%, and 86%, respectively. It is concluded that in patients with chronic LV dysfunction, the presence of total occlusion of coronary arteries supplying severely dyssynergic regions does not imply a lower prevalence or extent of functional recovery after revascularization, regardless of the grade of angiographically visualized collaterals. Low-dose DSE can identify myocardial regions with a high probability of functional improvement after revascularization regardless of the severity of underlying coronary stenosis or collateralization of the involved coronary vessel.

Collateral Circulation↗
PubMed1993

[The hemodynamics and anatomy of the circle of Willis. The technic and clinical value of selective MR angiography].

This study evaluates the usefulness of MR angiography in analysing the individual collateral flow dynamics and anatomy of the circle of Willis in 56 patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar area was performed by means of presaturation up to the brain-supplying arteries at the level of the middle neck (angled presaturation slabs). Results obtained with selective and non-selective MRA in 56 consecutive patients were compared with the findings at transcranial Doppler ultrasonography and arterial angiography. Ischaemic cerebral infarctions were classified by computerized tomography and correlated with the results of collateral flow analysis: Sensitivity of selective MRA in detecting intracranial collateral flow via anterior or posterior communicating artery was 96 and 97%, respectively; sensitivity in depicting extracranial transorbital flow was lower (71%). Non-selective MRA was 100% sensitive in detecting a non-filling of the horizontal (A1) segment of the anterior cerebral artery and in identifying an origin of the posterior cerebral artery from the intracranial carotid artery. Slow flow infarctions occurred more frequently in patients with transorbital and posterior-to-anterior collateral flow than in patients with collateral flow via anterior communicating artery.

Angiography↗
PubMed1986

In vivo characterization of a doxorubicin resistant B16 melanoma cell line.

A doxorubicin-resistant line of B16 melanoma (B16VDXR) was obtained in vitro by continuous exposure to increasing concentrations of doxorubicin of an in vitro line (B16V) derived from the in vivo transplanted B16 melanoma. When injected s.c. into mice, B16VDXR exhibited histological features, metastatic behaviour, doubling time and tumourigenic potential similar to those of the parental B16V line. Tumours obtained by implantation of B16VDXR, however, had longer latency and permitted a longer survival time than B16V and had, as in vitro, a higher DNA content. After i.v. inoculation, B16VDXR cells had lower lung colonizing capability compared to B16V. B16V and B16VDXR had significantly lower metastatic potential compared to the B16 melanoma from which they derived. Doxorubicin treatment significantly delayed the growth of B16 and B16V transplanted s.c. and increased the life span of animals bearing B16V. B16VDXR was resistant to doxorubicin treatment when the in vitro resistance index was greater than 100. While the doxorubicin-resistance phenotype was stable in vitro for 50 passages, in vivo the resistance phenotype was lost in 5 passages and tumours grown from s.c. inocula of mixtures of similar percentages of sensitive and resistant cells behaved as sensitive tumours. Cis-diamminedichloroplatinum (II), although marginally active in animals bearing B16V, was highly effective in B16VDXR bearing animals, suggesting a collateral cis-diamminedichloroplatinum (II) sensitivity of the B16VDXR line. After a single i.v. administration, doxorubicin reached initially, in the B16VDXR line, levels similar to those found in the B16 and B16V lines, but its release was faster from the resistant line in comparison with the sensitive ones. Doxorubicin-resistance was not overcome by more frequent treatments with doxorubicin. This doxorubicin-resistant tumour line obtained in vitro and used as a first in vivo transplant, may be a suitable metastaizing model for in vivo study of the mechanisms of resistance and of collateral sensitivity and for screening new drugs.

Animals↗
PubMedDate not supplied

Utility and limitations of splanchnic venous ultrasonography in diagnosis of portal hypertension.

The splanchnic venous system was examined by real-time ultrasonography in 46 patients with cirrhosis and documented portal hypertension and in 32 healthy subjects. Patients with portal hypertension had increased diameter of the splanchnic (portal, splenic, and superior mesenteric) veins (76% of patients), attenuation of the normal inspiratory increase in vein size (59%), and demonstrable portasystemic collateral vessels (umbilical or coronary veins or spontaneous splenorenal shunt) (44%). Splanchnic venous dimensions were significantly increased and changed less with respiration in patients with demonstrable portasystemic collaterals as compared to patients without these vessels. Portal pressure correlated only mildly with portal vein diameter (r = 0.30, p less than 0.05). Ultrasound abnormalities are present in a majority of patients with intrahepatic portal hypertension. However, because increased venous diameter and attenuated change in diameter with respiration are less frequent in patients lacking demonstrable portasystemic collaterals, the sensitivity of the test is least in those patients in whom its specificity is also limited.

Humans↗
PubMed2005

3He diffusion MRI of the lung.

RATIONALE AND OBJECTIVES: MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. RESULTS: We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. METHODS: Techniques for purging and imaging excised lungs are discussed.

Diffusion Magnetic Resonance Imaging↗
PubMed1995

Bacillus licheniformis bacitracin-resistance ABC transporter: relationship to mammalian multidrug resistance.

The nucleotide sequence of the Bacillus licheniformis bacitracin-resistance locus was determined. The presence of three open reading frames, bcrA, bcrB and bcrC, was revealed. The BcrA protein shares a high degree of homology with the hydrophilic ATP-binding components of the ABC family of transport proteins. The bcrB and bcrC genes were found to encode hydrophobic proteins, which may function as membrane components of the permease. Apart from Bacillus subtilis, these genes also confer resistance upon the Gram-negative Escherichia coli. The presumed function of the Bcr transporter is to remove the bacitracin molecule from its membrane target. In addition to the homology of the nucleotide-binding sites, BcrA protein and mammalian multidrug transporter or P-glycoprotein share collateral detergent sensitivity of resistant cells and possibly the mode of Bcr transport activity within the membrane. The advantage of the resistance phenotype of the Bcr transporter was used to construct deletions within the nucleotide-binding protein to determine the importance of various regions in transport.

ATP-Binding Cassette Transporters↗
PubMed1996

Induction of apoptosis in malignant and camptothecin-resistant human cells.

Flow cytometry studies demonstrate that androgen-independent human prostate carcinoma DU-145 cells are arrested at the G1-phase of the cell cycle in the presence of suramin, but they die by apoptosis in the presence of 9-nitrocamptothecin (9NC). The addition of cytostatic concentrations of suramin increases the apoptotic action of 9NC on DU-145 cells, and induces apoptosis in 9NC-resistant DU-145/RC cells that were derived from the parental DU-145 cells by continuous exposure to progressively increased concentrations of 9NC. In addition, the topoisomerase II-directed drug etoposide exerts more extensive apoptotic action on DU-145/RC than DU-145 cells. Increased resistance of DU-145 cells to 9 NC and collaterally increased sensitivity to etoposide and suramin appear to correlate with alterations in the structure rather than synthesis of topoisomerases and possibly with specific cellular proteins that regulate apoptosis. The results suggest that etoposide and suramin may be successful alternative treatments for 9NC-resistant androgen-independent prostate cancer.

Androgens↗
PubMed2000

Neuromuscular function of the human lower oesophageal sphincter in reflux disease and Barrett's oesophagus.

BACKGROUND: Columnar lined (Barrett's) oesophagus is often considered a sequel to chronic severe reflux disease. Aberrant lower oesophageal sphincter (LOS) motility associated with Barrett's oesophagus includes reduced basal LOS pressures. The aim of this study was to characterise neuromuscular function of the LOS in normal (squamous cell carcinoma (SCC) with uninvolved LOS) and reflux affected (Barrett's) oesophagus in vitro. METHODS: Strips of LOS muscle were prepared at biopsy following oesophagectomy from 16 patients with SCC and seven patients with oesophageal adenocarcinoma and Barrett's oesophagus associated with a history of reflux disease. LOS smooth muscle responses were recorded in response to electrical field stimulation (EFS), potassium chloride (KCl), DMPP, isoprenaline, capsaicin, bethanechol, and tachykinins. RESULTS: Basal LOS tone and LOS relaxations in response to isoprenaline, EFS, and DMPP were not significantly altered in the Barrett's group. After tetrodotoxin pretreatment, responses to KCl and DMPP were significantly reduced in the SCC but not in Barrett's LOS. Maximal contraction in response to bethanechol was significantly decreased in Barrett's LOS while substance P and NK-2 receptor mediated contraction was unaltered. Capsaicin, NK-1, and NK-3 receptor agonists exerted negligible effects on LOS tone. CONCLUSIONS: LOS muscle strips from patients with reflux associated Barrett's oesophagus exhibit a reduction in cholinergic muscle contraction while retaining similar features of basal tone, responses to tachykinins, and inhibitory muscle and neural function. Enteric inhibitory neurones in LOS muscle strips from patients with reflux associated Barrett's oesophagus display resistance to axonal sodium channel blockade. No evidence for functional NK-1 or NK-3 receptors or capsaicin sensitive axon collateral reflexes was observed in the human LOS.

Barrett Esophagus↗
PubMed1992

[Reassessment of radionuclide-venography for deep vein thrombosis in the lower extremities and pelvic cavity using 99mTc-MAA].

We performed radioisotope (RI)-venography in 31 patients suspected of deep vein thrombosis (DVT), and 18 patients of them (58.1%) had abnormal findings. Out of the 18 patients, 14 satisfied the diagnostic criteria for DVT, that were interruption in the venous flow with the presence of collateral circulation. Sensitivity, specificity and accuracy of RI-venography for DVT were 100%, 76%, 87%, respectively. In all of the patients with chief complaints of edema and pain in the unilateral extremity DVT was found by RI-venography. Lung scan revealed multiple pulmonary perfusion defects in 4 (33.3%) of 12 patients with DVT. Out of the 4 patients, 3 (75%) had silent pulmonary thromboembolism. 99mTc-MAA accumulation was seen in the left lobe of the liver in a patient with occlusion of the IVC and common iliac veins. We are convinced that patients with PTE and/or edema and pain in the unilateral lower extremity should undergo routine RI-venography. In conclusion, RI-venography using 99mTc-MAA was reassessed and we obtained the result that it is useful for screening and monitoring DVT and pulmonary thromboembolism.

Adolescent↗
PubMed1990

On the collateral sesamoidean (suspensory navicular) ligament of equines: topographic relations and sensitive innervation.

The origin and course of the collateral sesamoidean (suspensory navicular) ligament of the horse and ass and its attachment to the distal sesamoid bone were studied by means of dissection. Particular attention was given to the topographic relations between this ligament and the deep digital flexor tendon. Numerous sensitive nerve endings are present in this anatomical district. The free and encapsulated nerve endings, displayed by impregnating techniques, are mostly concentrated in the ligament tract connected to the above-named tendon and close to its attachment to the distal sesamoid angle. The nerve endings are identified as typical Pacini, Pacini-like and Golgi-Mazzoni corpuscles on account of their morphological features and are found isolated, grouped to form flower-sprays, lined up along the course of a single nerve fibre or grouped to originate poikilomorphous fibres.

Animals↗
PubMed2004

Altered calcium sensitivity contributes to enhanced contractility of collateral-dependent coronary arteries.

Coronary arteries distal to chronic occlusion exhibit enhanced vasoconstriction and impaired relaxation compared with nonoccluded arteries. In this study, we tested the hypotheses that an increase in peak Ca(2+) channel current density and/or increased Ca(2+) sensitivity contributes to altered contractility in collateral-dependent coronary arteries. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery (LCX) of female miniature swine. Segments of epicardial arteries ( approximately 1 mm luminal diameter) were isolated from the LCX and nonoccluded left anterior descending (LAD) arteries 24 wk after Ameroid placement. Contractile responses to depolarization (10-100 mM KCl) were significantly enhanced in LCX compared with size-matched LAD arterial rings [concentration of KCl causing 50% of the maximal contractile response (EC(50)); LAD = 41.7 +/- 2.3, LCX = 34.3 +/- 2.7 mM]. However, peak Ca(2+) channel current was not altered in isolated smooth muscle cells from LCX compared with LAD (-5.29 +/- 0.42 vs. -5.68 +/- 0.55 pA/pF, respectively). Furthermore, whereas half-maximal activation of Ca(2+) channel current occurred at nearly the same membrane potential in LAD and LCX, half-maximal inactivation was shifted to a more positive membrane potential in LCX cells. Simultaneous measures of contractile tension and intracellular free Ca(2+) (fura 2) levels in arterial rings revealed that significantly more tension was produced per unit change in fura 2 ratio in LCX compared with LAD in response to KCl but not during receptor-agonist stimulation with endothelin-1. Taken together, our data indicate that coronary arteries distal to chronic occlusion display increased Ca(2+) sensitivity in response to high KCl-induced depolarization, independent of changes in whole cell peak Ca(2+) channel current. Unaltered Ca(2+) sensitivity in endothelin-stimulated arteries suggests more than one mechanism regulating Ca(2+) sensitization in coronary smooth muscle.

Animals↗
PubMed1995

Transcranial Doppler ultrasound in the evaluation of collateral blood flow in patients with internal carotid artery occlusion: correlation with cerebral angiography.

PURPOSE: To determine the accuracy of transcranial Doppler (TCD) ultrasound for evaluation of collateral supply through the circle of Willis in patients with internal carotid artery (ICA) occlusion. METHODS: The evaluation of the collateral pathways through the circle of Willis with TCD ultrasound and with cerebral angiography was compared in 40 patients (30 men, 10 women; mean age, 55 +/- 9 years) in a total of 44 ICA occlusions of which 43 had a suitable ipsilateral temporal bone window for TCD examination. RESULTS: By TCD, a patent anterior communicating artery is indicated by a reversal blood flow in the A1-segment of the anterior cerebral artery or by a prompt fall of blood velocity in the middle cerebral artery after compression of the nonoccluded contralateral carotid artery. In 42 of 43 instances of ICA occlusion, TCD and angiography agreed in the evaluation of a present or absent anterior communicating artery collateral supply. TCD's sensitivity was 95%, its specificity 100%. A collateral supply through the basilar artery was assumed with TCD when there was: (a) a basilar artery blood velocity of more than 70 cm/s; (b) a marked increase of basilar artery blood velocity after compression of the nonoccluded carotid artery; (c) an evident side-to-side asymmetry of the blood velocity of the posterior cerebral arteries with high blood velocity ipsilateral to the ICA occlusion. For evaluating the collateralization via the basilar artery, TCD and angiography agreed in 37 of 40 ICA occlusions. TCD's sensitivity was 87%, its specificity 95%. CONCLUSIONS: TCD is a reliable tool for the evaluation of the collateral supply in patients with ICA occlusions.

Adult↗
PubMed1998

Collateral response to activation of potassium channels in vivo.

Activation of ATP-sensitive K+ channels is involved in the coronary vascular response to decreases in perfusion pressure and ischemia. Since activation of ATP-sensitive K+ channels in collateral vessels may be important in determining flow to collateral-dependent myocardium, the ability of collaterals to respond to activation of the channel was tested. In the beating heart of dogs, we compared responses of non-collaterals less than 100 microns in diameter to collaterals of similar size using computer-controlled stroboscopic epi-illumination of the left ventricle coupled to a microscope-video system. Aprikalim, a selective activator of ATP-sensitive K+ channels (0.1-10 microM) produced similar dose-dependent dilation of non-collaterals and collaterals. Relaxation was decreased by inhibition of ATP-sensitive K+ channels with glibenclamide, but not by inhibition of nitric oxide synthase with nitro-L-arginine. Bradykinin (10-100 microM) produced similar dilation of non-collaterals and collaterals which was decreased by nitro-L-arginine but not glibenclamide. Thus, in microvascular collaterals, relaxation to both nitric oxide and activation of ATP-sensitive K+ channels is similar to non-collaterals.

Acetylcholine↗
PubMed1975

Time-dependent changes of collateral coronary reactivity in the dog.

Vascular reactivity of the developing coronary collaterals has been investigated by studying local flow responses elicited by adrenergic and hypoxic stimuli in the ischemic foci of the canine heart. Tissue blood flow was measured by means of the heat clearance technique. The myocardial area explored was rendered ischemic by ligating the left anterior descending coronary artery 2-90 days prior to the experiment. This area is supplied exclusively by collateral channels. Adrenergic sensitivity was tested by i.v. administration or noradrenaline and isoproterenol (1 mug/kh), as well as by supramaximal electrical stimulation of the stellate ganglion. Metabolic sensitivity of the vessels was tested by brief periods of general hypoxia. During the first 3 weeks of the myocardial infarction, the collateral vascular response induced by each form of the adrenergic activation was considerably different from that observed in the normal coronary bed: instead of the conventional beta-type dilation, noradrenaline and stellate stimulation induced constriction in the ischemic zone whereas isoproterenol, having only pure beta-stimulating effects proved to be ineffective. Following the 3rd postoperative week, a gradually increasing sensitivity to beta-dilator influences appeared on the collateral vessels. However, this transformation of the adrenergic effect was not accompanied by a similar restoration of the local vascular propensity for metabolic (hypoxic) dilation. The results suggest that time courses of the changes of the adrenergic and metabolic vascular reactivity in the collateral network, although probably interrelated, do not parallel each other.

Animals↗
PubMed1997

Detection of coronary collaterals using dipyridamole PET myocardial perfusion imaging with rubidium-82.

UNLABELLED: This study evaluated the ability of dipyridamole PET myocardial perfusion imaging to detect coronary collaterals. A previous study showed an association between dipyridamole-induced coronary steal on PET imaging and the presence of coronary collaterals on angiography. METHODS: Dipyridamole PET myocardial perfusion imaging using 82Rb was performed in 45 patients who had recent coronary angiography. The stress/rest count ratio (rubidium activity with stress divided by activity at rest)-was used to express the change in regional tracer uptake with dipyridamole and was calculated manually and automatically. The accuracy of the stress/rest count ratio for detecting coronary collaterals was determined. RESULTS: A manual stress/rest count ratio < or = 0.80 identified coronary collaterals with 81% sensitivity, 92% specificity and 90% accuracy (p < 0.0001). An automated ratio < or = 0.80 had 90% sensitivity, 88% specificity and 90% accuracy (p < 0.0001). Vascular beds incorrectly identified by PET as having collaterals had an increased frequency of severe stenoses and abnormal wall motion. CONCLUSION: PET perfusion imaging using the stress/rest count ratio can serve as a unique imaging method to identify coronary collaterals noninvasively.

Collateral Circulation↗
PubMed1996

Limitation of sensitization to injured parts of receptive fields in human skin C-nociceptors.

Unmyelinated cutaneous mechano-heat fibers (CMH) in the peroneal nerve of healthy human volunteers were studied by means of a "marking" technique which allows stable recordings from identified single units over extended periods. Mechanoreceptive field sizes were 105 +/- 13 mm2 in 25 units. These large receptive fields indicate extensive terminal branching of C fibers in the skin of foot and lower leg. Sensitization of CMHs was tested by assessment of thresholds for mechanical (von Frey hair) and heat stimuli before and after topical application of mustard oil (allyl isothiocyanate) and capsaicin (8-methyl-N-vanillyl-6-noneamide). While in a group of 14 CMHs the entire receptive field was treated with these irritant substances, in another group of 11 CMH units only parts of the receptive field were treated to check for signs of spreading sensitization through axon collaterals. Mustard oil application did not change mechanical thresholds, regardless of whether parts of or complete receptive fields were treated. However, mean heat thresholds dropped by 5.6 degrees C to 36.5 +/- 1.5 degrees C in completely treated receptive fields and by 5.7 degrees C to 37.3 +/- 3.4 degrees C in treated parts of receptive fields ("primary sensitization"). In contrast, heat thresholds in the nontreated parts did not change significantly (42.1 +/- 3.4 degrees C vs 41.2 +/- 3.9 degrees C), i.e. "secondary sensitization" to heat was lacking. The absence of primary sensitization to probing with von Frey hairs indicates that sensitization of insensitive C fibers and recruitment of insensitive axon collaterals may be more important for mechanical hyperalgesia than sensitization of conventional CMH units-apart from the contribution of central mechanisms. The lack of spread of sensitization to untreated parts of the receptive fields o CMHs ("secondary sensitization") indicates that this fiber group is probably not involved in any form of secondary hyperalgesia to heating.

Adult↗