Antidromic vasodilatation and neurogenic inflammation

Chahl, Loris A.

doi:10.1016/0163-7258(88)90029-0

Cited by 135 publications

(51 citation statements)

References 209 publications

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“…Current-induced vasodilation is well recognized and is most likely secondary to activation of polymodal Cfiber nociceptors (9,49). The increase in blood flow inside the iontophoretic zone was significantly attenuated by EMLA treatment.…”

Section: Ach-mediated Cutaneous Microcirculatory Vasodilationmentioning

confidence: 90%

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Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Berghoff

Kathpal

Kilo

et al. 2002

Journal of Applied Physiology

109

118

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nisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation. J Appl Physiol 92: 780-788, 2002; 10.1152/japplphysiol.01167.2000.-The relative contribution of endothelial vasodilating factors to acetylcholine (ACh)-mediated vasodilation in the forearm cutaneous microcirculation is unclear. The aims of this study were to investigate the contributions of prostanoids and cutaneous C fibers to basal cutaneous blood flow (CuBF) and ACh-mediated vasodilation. ACh was iontophoresed into the forearm, and cutaneous perfusion was measured by laser-Doppler flowmetry. To inhibit the production of prostanoids, four doses of acetylsalicylic acid (ASA; 81, 648, 972, and 1,944 mg) were administered orally. Cutaneous nerve fibers were blocked with topical anesthesia. Cyclooxygenase inhibition did not change basal CuBF or endothelium-mediated vasodilation to ACh. In contrast, ASA (972 and 1,944 mg) significantly reduced the C-fiber-mediated axon reflex in a dose-dependent fashion. Blockade of C-fiber function significantly reduced axon reflex-mediated vasodilation but did not affect basal CuBF or endothelium-dependent vasodilation. The findings suggest that prostanoids do not contribute significantly to basal CuBF or endothelium-dependent vasodilation in the forearm microcirculation. In contrast, prostanoids are mediators of the ACh-provoked axon reflex. endothelium; prostaglandin; nitric oxide; axon reflex; acetylcholine CUTANEOUS BLOOD FLOW (CuBF) is regulated by endothelial, neural, and humoral factors. The interaction between these mechanisms of blood flow control is poorly defined. Recent studies of CuBF have used the technique of laser-Doppler flowmetry in combination with the iontophoretic application of charged vasoactive agents. Acetylcholine (ACh) has been used to induce endothelium-mediated blood flow, and the direct nitric oxide (NO) donor sodium nitroprusside has been used to provoke non-endothelium-mediated blood flow. Despite the widespread use of ACh-evoked vasodilation in studies investigating vascular physiology and pathophysiology, the mechanisms responsible for its effect, particularly in the cutaneous microcirculation, are unresolved. This question has important implications. If prostaglandins do play a major role in endotheliummediated vasodilation, some effects of acetylsalicylic acid (ASA) therapy, which is extensively used for its prophylactic antiplatelet effect in patients with cardiovascular and cerebrovascular disease (17, 27), may be counterproductive. Furthermore, if prostaglandins play a major role in the C-fiber-mediated axon reflex, reduction of this reflex by cyclooxygenase inhibition may attenuate the ability to mount a neurogenic inflammatory response (4, 48). Attenuation of this important protective reflex in patients with peripheral neuropathy impairs wound healing and increases susceptibility to infection, thereby leading to cutaneous ulceration, gangrene, and ultimately amputation (3,21).Factors released by the endothelium in response to ACh include NO, vasoactive prostanoi...

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Section: Ach-mediated Cutaneous Microcirculatory Vasodilationmentioning

confidence: 90%

“…This possibility was suggested by Forst et al (22), who proposed that the effect of intracutanous ACh on CuBF is mediated mainly by the axon reflex. The situation is more complex, however, as there is evidence that the iontophoretic current alone may also induce an axon reflex (9). Furthermore, prostaglandins may play a role in the axon reflex.…”

mentioning

confidence: 85%

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Berghoff

Kathpal

Kilo

et al. 2002

Journal of Applied Physiology

109

118

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“…A physiological operating range of nociceptive afferents at monkey hairy skin to these repetitive temperature steps is discharge rates that are not transmitted across central synapses (i.e. remain below conscious perception) was first postulated by Janos Szolcsanyi (Chahl et al 1984). Indeed, low-grade activity down to a few action potentials at several seconds interval is sufficient for release of neuropeptides, most notably CGRP, from the peripheral terminals of nociceptive afferents (for review see Holzer, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…The peripheral release of substance P and calcitonin gene-related peptide (CGRP) causes hyperaemia by dilatation of arterioles and plasma extravasation by leakage at postcapillary venules (Holzer, 1992). These peripheral consequences of nociceptor activation are collectively termed neurogenic inflammation (Chahl et al 1984), because they match the cardinal signs of inflamnmation (calor, rubor, tumor). The vasodilatation component of neurogenic inflammation is one of several mechanisms (in addition to endothelium-dependent and metabolic vasodilatation) that counteract the vasoconstriction due to sympathetic innervation and circulating catecholamines.…”

mentioning

confidence: 99%

Heat‐evoked vasodilatation in human hairy skin: axon reflexes due to low‐level activity of nociceptive afferents.

Magerl

Treede

1996

The Journal of Physiology

133

112

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1. Spreading vasodilatation of the axon reflex type was evoked by contact heat stimulation of the hairy skin in the human forearm (13X3 cm2 stimulus area) and was detected by laser Doppler flowmetry at 8, 19 and 30 mm distance.2. From a base temperature of 350, rapidly rising short heat stimuli (4°C s-1, 2 s plateau) elicited vasodilatation at an average threshold of 39 4 0C. For slowly rising sustained heat stimuli (64 s duration) the average threshold was 39-6 0C (n.s.). Laser Doppler flowmetry revealed a rapid onset within about 4 s, a long duration of several minutes beyond the end of the stimulus, and a rapid spread of vasodilatation to remote skin areas. These characteristics are typical for vasodilatation by an axon reflex of nociceptive afferents. 3. Axon reflex thresholds matched the lower range of C fibre nociceptor heat thresholds.Thermal stimuli that were adjusted to elicit about half-maximal phasic responses in warm fibres (steps from 30 to 350), but were below the range of C fibre nociceptor thresholds, did not cause any vasodilatation. 4. Pain thresholds were higher than axon reflex thresholds for both rapidly and slowly rising heat stimuli and strongly depended on the stimulus pattern (40-1 0C for rapidly rising stimuli and >430C for slowly rising stimuli). This observation is consistent with recent reports that the phasic response of nociceptive afferents is essential to overcome the summation requirements at central synapses. 5. In conclusion, axon reflex vasodilatation in response to heat stimuli in the hairy skin of humans is elicited by activation of heat-sensitive nociceptors, even in the absence of a conscious perception of heat pain. The dissociation of pain and vasodilatation thresholds supports the concept of two operating ranges of primary nociceptive afferents. Warm fibres do not contribute to axon reflex vasodilatation in the hairy skin of the human forearm. Release of vasoactive peptides by nociceptive primary afferents may also contribute to local heat-evoked vasodilatation at temperatures above 400C.

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“…These sensory neurones play a dual, sensory and 'efferent' function (Szolcsanyi, 1984;Maggi & Meli, 1986;, the latter being determined by transmitter release from peripheral nerve endings at the time of sensory receptor stimulation. Strong pharmacological and physiological evidence indicates that TKs release in the periphery takes place during the well-known phenomenon of 'neurogenic inflammation' (Lembeck & Holzer, 1979; see Chahl, 1988 andHolzer, 1988 for review). Nilsson et al (1985) reported that TKs exert a potent stimulant action on proliferation of human skin fibroblasts and, on this basis, a possible role of endogenous TKs on wound healing was suggested (see also Maggi et al, 1987a;Kjartansson et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

NK₁‐receptors mediate the proliferative response of human fibroblasts to tachykinins

Ziche¹,

Morbidelli

Pacini

et al. 1990

British J Pharmacology

102

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1The effect of synthetic tachykinin selective receptor agonists was studied on the growth of cultured human skin fibroblasts (HF). 2 Human fibroblasts were grown in serum-free conditions in the presence of natural tachykinins (substance P and neurokinin A) and of three synthetic agonists, [fl-Ala4, Sar9, Met (02) Cell proliferation was measured by percentage increase in cell number and by [3H]-thymidine uptake following 48 h exposure to agents compared to baseline condition. 3 Neurokinin A (NKA) and substance P (SP) significantly increased cell proliferation the threshold concentrations being 10-12 and 10-11 M, respectively. Addition of thiorphan to culture conditions enhanced the effect of SP but not of NKA.4 The selective NK1-receptor agonist produced a dose-dependent increase in cell proliferation as judged by total cell number and [3H]-thymidine uptake. No significant effect was observed with NK2-and NK3-receptor agonists. 5 These data indicate that the effect of SP on fibroblast proliferation is mediated by interaction with a NK1-receptor type and local metabolism can interfere with the full expression of this effect of SP on cell proliferation.

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Antidromic vasodilatation and neurogenic inflammation

Cited by 135 publications

References 209 publications

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Heat‐evoked vasodilatation in human hairy skin: axon reflexes due to low‐level activity of nociceptive afferents.

NK₁‐receptors mediate the proliferative response of human fibroblasts to tachykinins

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Antidromic vasodilatation and neurogenic inflammation

Cited by 135 publications

References 209 publications

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Vascular and neural mechanisms of ACh-mediated vasodilation in the forearm cutaneous microcirculation

Heat‐evoked vasodilatation in human hairy skin: axon reflexes due to low‐level activity of nociceptive afferents.

NK1‐receptors mediate the proliferative response of human fibroblasts to tachykinins

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NK₁‐receptors mediate the proliferative response of human fibroblasts to tachykinins