Roles of TRPV<sub>1</sub> and Neuropeptidergic Receptors in Dorsal Root Reflex-Mediated Neurogenic Inflammation Induced by Intradermal Injection of Capsaicin

Lin, Qing; Li, Dingge; Xu, Xijin; Zou, Xiaoju; Li, Fang

doi:10.1186/1744-8069-3-30

Cited by 78 publications

(96 citation statements)

References 56 publications

(93 reference statements)

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“…In addition it is established, that though tachykinins are in most conditions potent vasodilators, in different models or species they can induce vasoconstriction, and that their net effect is heavily influenced by the local differences of the endothelium [58]. This assumption also correlates with the fact, that so far no substance could be labeled as the exclusive mediator of cutaneous vasodilation [4,24].…”

Section: Discussionmentioning

confidence: 87%

“…It should be noted that the well established effect of SP in neurogenic inflammation is increasing venular permeability, a phenomen which was not measured with the laser Doppler scanning [19]. In addition, CGRP is considered as the most potent mediator of vasodilation [24]. It was suggested, that the NK 1 receptor activation serves to increase indirectly the production of nitric oxide (NO) and other local vasodilatory substances, however it is accepted, that there is a lot of interactions between the neuropeptides, local mediators, and receptors involved in this process, and the responsible pathways are redundant [59].…”

Section: Discussionmentioning

confidence: 99%

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Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

et al. 2013

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a b s t r a c tPituitary Adenylate-Cyclase Activating Polypeptide (PACAP) and Tac1 gene-encoded tachykinins (substance P: SP, neurokinin A: NKA) are expressed in capsaicin-sensitive nerves, but their role in nociception, inflammation and vasoregulation is unclear. Therefore, we investigated the function of these neuropeptides and the NK 1 tachykinin receptor (from Tacr1 gene) in the partial sciatic nerve ligationinduced traumatic mononeuropathy model using gene deficient (PACAP −/− , Tac1 −/− , and Tacr1 −/− ) mice. Mechanonociceptive threshold of the paw was measured with dynamic plantar aesthesiometry, motor coordination with Rota-Rod and cutaneous microcirculation with laser Doppler imaging. Neurogenic vasodilation was evoked by mustard oil stimulating sensory nerves. In wildtype mice 30-40% mechanical hyperalgesia developed one week after nerve ligation, which was not altered in Tac1−/− and Tacr1mice, but was absent in PACAP −/− animals. Motor coordination of the PACAP −/− and Tac1 −/− groups was significantly worse both before and after nerve ligation compared to their wildtypes, but it did not change in Tacr1−/− mice. Basal postoperative microcirculation on the plantar skin of PACAP −/− mice did not differ from the wildtypes, but was significantly lower in Tac1 −/− and Tacr1 −/− ones. In contrast, mustard oil-induced neurogenic vasodilation was significantly smaller in PACAP −/− mice, but not in Tacr1 −/− and Tac1 −/− animals. Both PACAP and SP/NKA, but not NK 1 receptors participate in normal motor coordination. Tachykinins maintain basal cutaneous microcirculation. PACAP is a crucial mediator of neuropathic mechanical hyperalgesia and neurogenic vasodilation. Therefore identifying its target and developing selective, potent antagonists, might open promising new perspectives for the treatment of neuropathic pain and vascular complications.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

et al. 2013

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“…The released substances produce a myriad of autocrine or paracrine effects on endothelial, epithelial, and resident immune cells (Langerhans), which lead to arteriolar vasodilatation ("flare," via CGRP) and/or increased vascular permeability and plasma extravasation from venules (edema, via substance P). Liberated enzymes (e.g., kallikreins) and blood cells (e.g., platelets, mast cells) further contribute to the accumulation of inflammatory mediators and neurogenic inflammation (110,111). A large variety of substances feed back onto nociceptors innervating the injured region and sensitize peripheral terminals by direct and indirect actions at ion channels, receptors, and second messenger cascades (87,102,111,112).…”

Section: Adaptive and Maladaptive Shifts In Pain Thresholdmentioning

confidence: 99%

Nociceptors: the sensors of the pain pathway

Dubin

Patapoutian²

2010

J. Clin. Invest.

960

856

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Specialized peripheral sensory neurons known as nociceptors alert us to potentially damaging stimuli at the skin by detecting extremes in temperature and pressure and injury-related chemicals, and transducing these stimuli into long-ranging electrical signals that are relayed to higher brain centers. The activation of functionally distinct cutaneous nociceptor populations and the processing of information they convey provide a rich diversity of pain qualities. Current work in this field is providing researchers with a more thorough understanding of nociceptor cell biology at molecular and systems levels and insight that will allow the targeted design of novel pain therapeutics.

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“…The TRPV-1 isoform has been shown to be activated by heat and capsaicin (2,19,27). Although TRPV-1 channels are located predominantly on afferent sensory nerves and Charkoudian et al (3) found no effect of acute and chronic capsaicin treatment on reflex cutaneous vasodilation, it is possible alternative sources/locations of TRPV-1 channels contribute to reflex cutaneous vasodilation.…”

mentioning

confidence: 99%

Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans

Wong

Fieger

2012

Journal of Applied Physiology

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Wong BJ, Fieger SM. Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans. J Appl Physiol 112: 2037-2042, 2012. First published April 19, 2012 doi:10.1152/japplphysiol.00209.2012.-Mechanisms underlying the cutaneous vasodilation in response to an increase in core temperature remain unresolved. The purpose of this study was to determine a potential contribution of transient receptor potential vanilloid type 1 (TRPV-1) channels to reflex cutaneous vasodilation. Twelve subjects were equipped with four microdialysis fibers on the ventral forearm, and each site randomly received 1) 90% propylene glycol ϩ 10% lactated Ringer (vehicle control); 2) 10 mM L-NAME; 3) 20 mM capsazepine to inhibit TRPV-1 channels; 4) combined 10 mM L-NAME ϩ 20 mM capsazepine. Whole body heating was achieved via water-perfused suits sufficient to raise oral temperature at least 0.8°C above baseline. Maximal skin blood flow was achieved by local heating to 43°C and infusion of 28 mM nitroprusside. Systemic arterial pressure (SAP) was measured, and skin blood flow was monitored via laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as LDF/SAP and normalized to maximal vasodilation (%CVC max). Capsazepine sites were significantly reduced compared with control (50 Ϯ 4%CVC max vs. 67 Ϯ 5%CVC max, respectively; P Ͻ 0.05). L-NAME (33 Ϯ 3%CVCmax) and L-NAME ϩ capsazepine (30 Ϯ 4%CVCmax) sites were attenuated compared with control (P Ͻ 0.01) and capsazepine (P Ͻ 0.05); however, there was no difference between L-NAME and combined L-NAME ϩ capsazepine. These data suggest TRPV-1 channels participate in reflex cutaneous vasodilation and TRPV-1 channels may account for a portion of the NO component. TRPV-1 channels may have a direct neural contribution or have an indirect effect via increased arterial blood temperature. Whether the TRPV-1 channels directly or indirectly contribute to reflex cutaneous vasodilation remains uncertain. microdialysis; heat stress; nitric oxide INCREASES IN SKIN BLOOD FLOW and sweating represent humans' primary physiological defense against an increase in core temperature. The initial increase in skin blood flow during hyperthermia is driven primarily by withdrawal of tonic sympathetic vasoconstrictor tone, which results in approximate doubling of resting thermoneutral skin blood flow(8, 23). Further increases in skin blood flow, concomitant with the onset of sweating, are mediated by reflex sympathetic cholinergic nerve activity (8). This reflex cutaneous active vasodilation accounts for 85-95% of the increase in skin blood flow during hyperthermia and can result in nearly 8 liters/min of cardiac output directed to the cutaneous vasculature(24).The co-transmission theory of cutaneous active vasodilation suggests acetylcholine and one or more unknown vasodilators are co-released from sympathetic cholinergic nerves, where acetylcholine is primarily responsible for the sweat response and the unknown vasodilator(s) are responsible for the refle...

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Roles of TRPV₁ and Neuropeptidergic Receptors in Dorsal Root Reflex-Mediated Neurogenic Inflammation Induced by Intradermal Injection of Capsaicin

Cited by 78 publications

References 56 publications

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Nociceptors: the sensors of the pain pathway

Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans

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Roles of TRPV1 and Neuropeptidergic Receptors in Dorsal Root Reflex-Mediated Neurogenic Inflammation Induced by Intradermal Injection of Capsaicin

Cited by 78 publications

References 56 publications

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

Nociceptors: the sensors of the pain pathway

Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans

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Roles of TRPV₁ and Neuropeptidergic Receptors in Dorsal Root Reflex-Mediated Neurogenic Inflammation Induced by Intradermal Injection of Capsaicin