Longitudinal Study of Functional Reinnervation of the Denervated Skin by Collateral Sprouting of Peptidergic Nociceptive Nerves Utilizing Laser Doppler Imaging

Lakatos, Szandra; Jancsó, Gábor; Horváth, Ágnes; Dobos, Ildikó; Stella, Péter

doi:10.3389/fphys.2020.00439

Cited by 9 publications

(15 citation statements)

References 63 publications

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“…Recently, we have developed a novel experimental approach which permits the longitudinal assessment of the functional regeneration of peptidergic nociceptive afferents following peripheral nerve transection. The technique is based on the assessment of the intensity and spatial distribution of mustard oil–induced changes in skin blood flow by utilizing scanning laser Doppler imaging [ 16 ]. Mustard oil is an agonist of transient receptor potential ankyrin type 1 (TRPA1) receptors [ 17 ], which are expressed in all TRPV1 receptor–expressing nociceptive primary sensory neurons [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that skin areas delineated by mustard oil–induced increased vascular permeability as assessed with the Evans blue method [ 14 , 15 , 25 , 26 , 27 ] or the vascular labeling technique [ 7 ] correspond to the innervation territories of nerve endings stimulated by antidromic electrical nerve stimulation or the direct application of chemical irritants onto the skin. Importantly, cutaneous areas displaying sensory nerve stimulation–induced vasodilatation and plasma extravasation are strictly coincident with the innervation territory of the stimulated nerve [ 7 , 16 , 28 ]. Therefore, topographical localization of mustard oil–induced vasodilatation and plasma extravasation can be used to assess the pattern of cutaneous innervation in naïve and nerve-injured animals [ 14 , 15 , 16 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, cutaneous areas displaying sensory nerve stimulation–induced vasodilatation and plasma extravasation are strictly coincident with the innervation territory of the stimulated nerve [ 7 , 16 , 28 ]. Therefore, topographical localization of mustard oil–induced vasodilatation and plasma extravasation can be used to assess the pattern of cutaneous innervation in naïve and nerve-injured animals [ 14 , 15 , 16 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Perineural Capsaicin Treatment Inhibits Collateral Sprouting of Intact Cutaneous Nociceptive Afferents

et al. 2022

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Perineural treatment of peripheral nerves with capsaicin produces a long-lasting selective regional thermo- and chemo-analgesia and elimination of the neurogenic inflammatory response involving degeneration of nociceptive afferent fibers. In this study, we examined longitudinal changes in mustard oil–induced sensory neurogenic vasodilatation and plasma extravasation following perineural capsaicin treatment of the rat saphenous nerve utilizing scanning laser Doppler imaging and vascular labeling with colloidal silver. Capsaicin treatment resulted in a marked decrease in mustard oil–induced vasodilatation in the skin area served by the saphenous nerve. Repeated imaging of the vasodilatatory response showed no recovery for at least 7 weeks. However, following transection and ligation of the capsaicin-treated saphenous nerve, a substantial recovery of the vasodilatatory response was observed, suggesting a reinnervation of the chemodenervated skin area by collateral sprouting of neighboring intact sciatic nerve afferents. Elimination of the recovered vascular reaction by capsaicin treatment of the sciatic nerve supported this conclusion. Similar results have been obtained by using the vascular labeling technique. These findings indicate an inhibitory effect of persisting cutaneous nerve fibers on the collateral sprouting of intact nerve fibers into the chemodenervated skin area. These observations may bear implications for the development of sensory disturbances following peripheral nerve injuries.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Perineural Capsaicin Treatment Inhibits Collateral Sprouting of Intact Cutaneous Nociceptive Afferents

et al. 2022

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“…We hypothesised that the LDI local heating test data will reflect cutaneous vasomotor dysfunction, including significant changes in the sensory axonal reflex and endothelium-dependent vasodilation in migraine patients and that the results of this test will correlate with blood levels of proinflammatory chemokines IL-8. LDI is a reliable technique for the measurement of cutaneous blood flow under physiological and pathophysiological conditions, including for measurement of thermoregulatory vascular responses (Lakatos et al, 2020). The skin blood flow response to local, rapid heating below the pain threshold ( ~43°C) is different from the mechanisms that increase microvascular blood flow in response to an increased overall temperature of the body.…”

Section: Introductionmentioning

confidence: 99%

Influence of Migraine on Axon Reflex-Mediated and Endothelial-Dependent Vasodilatation in the Skin

Plinta

Tretjakovs

Logina

et al. 2021

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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The aim of the study was to evaluate the changes in skin blood flow as a result of local heating tests in migraine patients during the interictal period, measured by laser Doppler perfusion imaging (LDI). The aim of the study was also to estimate the correlations between the results of these tests and interleukin (IL)-8 levels. Twelve migraine patients during their interictal period were compared with twelve healthy control subjects. Only women were included in the study. Both groups were matched with regard of their age, body mass index and blood pressure. For the purpose of measuring cutaneous microvascular blood flow, heating (+44 °C) of the dorsal side of the palm as a response to the local LDI was used. IL-8 was measured in serum by ELISA method. The findings suggested that migraine patients have a cutaneous vasomotor dysfunction during the interictal period. The results showed a significant decrease in the initial peak of vasodilation and the second peak of vasodilation (plateau phase). Also there were significant changes observed in the length of the time interval required to reach the first and second vasodilation peak. It is known that migraine patients have a shorter time interval to reach the first perfusion peak (axonal reflex-mediated) and longer time interval to reach the second peak (endothelium-dependent). The results confirmed the correlation between proinflammatory chemokine IL-8 levels, and the time interval till the second peak of blood flow in all study subjects.

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“…Thus, noxious stimuli activate morphologically complex excitable structures, which differ among primary nociceptive neurons. Importantly, the morphology of terminal trees changes with age or under pathological conditions (Cain et al, 2001;Chartier et al, 2018;Lakatos et al, 2020;Leibovich et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The Input-Output Relation of Primary Nociceptive Neurons is Determined by the Morphology of the Peripheral Nociceptive Terminals

et al. 2020

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The output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree.The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential firing. However, in the majority of cases, noxious stimuli activate multiple terminals; thus, the output of the nociceptive neuron is defined by the integration and computation of the inputs of the individual terminals. Here we used a computational model of nociceptive terminal tree to study how the architecture of the terminal tree affects input-output relation of the primary nociceptive neurons. We show that the input-output properties of the nociceptive neurons depend on the length, the axial resistance, and location of individual terminals. Moreover, we show that activation of multiple terminals by capsaicin-like current allows summation of the responses from individual terminals, thus leading to increased nociceptive output. Stimulation of terminals in simulated models of inflammatory or nociceptive hyperexcitability led to a change in the temporal pattern of action potential firing, emphasizing the role of temporal code in conveying key information about changes in nociceptive output in pathological conditions, leading to pain hypersensitivity.

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Longitudinal Study of Functional Reinnervation of the Denervated Skin by Collateral Sprouting of Peptidergic Nociceptive Nerves Utilizing Laser Doppler Imaging

Cited by 9 publications

References 63 publications

Perineural Capsaicin Treatment Inhibits Collateral Sprouting of Intact Cutaneous Nociceptive Afferents

Perineural Capsaicin Treatment Inhibits Collateral Sprouting of Intact Cutaneous Nociceptive Afferents

Influence of Migraine on Axon Reflex-Mediated and Endothelial-Dependent Vasodilatation in the Skin

The Input-Output Relation of Primary Nociceptive Neurons is Determined by the Morphology of the Peripheral Nociceptive Terminals

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