Multi-Channel Bioimpedance System for Detecting Vascular Tone in Human Limbs: An Approach

Vascular tone plays a vital role in regulating blood pressure and coronary circulation, and it determines the peripheral vascular resistance. Vascular tone is dually regulated by the perivascular nerves and the cells in the inside lining of blood vessels (endothelial cells). Only a few methods for measuring vascular tone are available. Because of this, determining vascular tone in different arteries of the human body and monitoring tone changes is a vital challenge. This work presents an approach for determining vascular tone in human extremities based on multi-channel bioimpedance measurements. Detailed steps for processing the bioimpedance signals and extracting the main parameters from them have been presented. A graphical interface has been designed and implemented to display the vascular tone type in all channels with the phase of breathing during each cardiac cycle. This study is a key step towards understanding the way vascular tone changes in the extremities and how the nervous system regulates these changes. Future studies based on records of healthy and diseased people will contribute to increasing the possibility of early diagnosis of cardiovascular diseases.

Intra-arterial instillation of a nociceptive agent modulate cardiorespiratory parameters involving 5-HT3 and TRPV1 receptors in anesthetized rats

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

Innervation of the human intervertebral disc: a scoping review

Objective: Back pain is an elusive symptom complicated by a variety of possible causes, precipitating and maintaining factors, and consequences. Notably, the underlying pathology remains unknown in a significant number of cases. Changes to the intervertebral disc (IVD) have been associated with back pain, leading many to postulate that the IVD may be a direct source of pain, typically referred to as discogenic back pain. Yet, despite decades of research into the neuroanatomy of the IVD, there is a lack of consensus in the literature as to the distribution and function of neural elements within the tissue. The current scoping review provides a comprehensive systematic overview of studies that document the topography, morphology, and immunoreactivity of neural elements within the IVD in humans. <uMel>thod: Articles were retrieved from six separate databases in a three-step systematic search, and independently evaluated by two reviewers. <Resul>ults: Three categories of neural elements were described within the IVD: perivascular nerves, sensory nerves independent of blood vessels, and mechanoreceptors. Nerves were consistently localized within the outer layers of the annulus fibrosus. Neural ingrowth into the inner annulus fibrosus and nucleus pulposus was found to occur only in degenerative states and disease states. Conclusion: While the pattern of innervation within the IVD is clear, the specific topographic arrangement and function of neural elements in the context of back pain remains unclear.

Comparison of Adrenergic and Purinergic Receptor Contributions to Vasomotor Responses in Mesenteric Arteries of C57BL/6J Mice and Wistar Rats

<b><i>Introduction:</i></b> The sympathetic nervous system can modulate arteriolar tone through release of adenosine triphosphate and norepinephrine, which bind to purinergic and adrenergic receptors (ARs), respectively. The expression pattern of these receptors, as well as the composition of neurotransmitters released from perivascular nerves (PVNs), can vary both in organ systems within and across species, such as mice and rats. <b><i>Objective:</i></b> This study explores the function of α_1A subtypes in mouse and rat third-order mesenteric arteries and investigates PVN-mediated vasoconstriction to identify which neurotransmitters are released from sympathetic PVNs. <b><i>Methods:</i></b> Third-order mesenteric arteries from male C57BL/6J mice and Wistar rats were isolated and mounted on a wire myograph for functional assessment. Arteries were exposed to phenylephrine (PE) and then incubated with either α_1A antagonist RS100329 (RS) or α_1D antagonist BMY7378, before reexposure to PE. Electrical field stimulation was performed by passing current through platinum electrodes positioned adjacent to arteries in the absence and presence of a nonspecific alpha AR blocker phentolamine and/or P2X₁-specific purinergic receptor blocker NF449. <b><i>Results:</i></b> Inhibition of α₁ ARs by RS revealed that PE-induced vasoconstriction is primarily mediated through α_1A and that the contribution of the α_1A AR is greater in rats than in mice. In the mouse model, sympathetic nerve-mediated vasoconstriction is mediated by both ARs and purinergic receptors, whereas in rats, vasoconstriction appeared to only be mediated by ARs and a nonpurinergic neurotransmitter. Further, neither model demonstrated that α_1D ARs play a significant role in PE-mediated vasoconstriction. <b><i>Conclusions:</i></b> The mesenteric arteries of male C57BL/6J mice and Wistar rats have subtle differences in the signaling mechanisms used to mediate vasoconstriction. As signaling pathways in humans under physiological and pathophysiological conditions become better defined, the current study may inform animal model selection for preclinical studies.

Acetaminophen (Paracetamol) Metabolites Induce Vasodilation and Hypotension by Activating Kv7 Potassium Channels Directly and Indirectly

Objective: Intravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation. Conclusions: Direct and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.

Instillation of bradykinin into femoral artery elicits cardiorespiratory reflexes involving perivascular afferents in anesthetized rats

The physiology of baroreceptors and chemoreceptors present in large blood vessels of the heart is well known in the regulation of cardiorespiratory functions. Since large blood vessels and peripheral blood vessels are of the same mesodermal origin, therefore, involvement of the latter in the regulation of cardiorespiratory system is expected. The role of perivascular nerves in mediating cardiorespiratory alterations produced after intra-arterial injection of a nociceptive agent (bradykinin) was examined in urethane-anesthetized male rats. Respiratory frequency, blood pressure, and heart rate were recorded for 30 min after the retrograde injection of bradykinin/saline into the femoral artery. In addition, paw edema was determined and water content was expressed as percentage of wet weight. Injection of bradykinin produced immediate tachypneic, hypotensive and bradycardiac responses of shorter latency (5–8 s) favoring the neural mechanisms involved in it. Injection of equi-volume of saline did not produce any responses and served as time-matched control. Paw edema was observed in the ipsilateral hind limb. Pretreatment with diclofenac sodium significantly attenuated the bradykinin-induced responses and also blocked the paw edema. Ipsilateral femoral and sciatic nerve sectioning attenuated bradykinin-induced responses significantly, indicating the origin of responses from the local vascular bed. Administration of bradykinin in the segment of an artery produced reflex cardiorespiratory changes by stimulating the perivascular nociceptors involving prostaglandins. This is a novel study exhibiting the role of peripheral blood vessels in the regulation of the cardiorespiratory system.

Effect of Electroacupuncture on Hyperalgesia and Vasoactive Neurotransmitters in a Rat Model of Conscious Recurrent Migraine

Migraine onset is associated with the abnormal release of vasoactive neurotransmitters from perivascular nerves, and these neurotransmitters are involved in the pathophysiology of migraine. Hyperalgesia is a key feature of migraine, and accumulating evidence indicates that electroacupuncture (EA) at the single acupuncture point (Fengchi [GB20]) is effective in ameliorating hyperalgesia. In clinical practice, multiple acupuncture points are widely used, especially GB20 and Yanglingquan (GB34). However, the role played by vasoactive neurotransmitters in acupuncture antihyperalgesic effect at the single or multiple acupuncture points remains unknown. We aimed to determine whether EA would exert its antihyperalgesic effects by modulating vasoactive neurotransmitter release from the perivascular nerves. Furthermore, we examined whether targeting multiple acupuncture points would be more effective than targeting a single point in reducing hyperalgesia. The mechanical and thermal hyperalgesia were evaluated by measuring the facial and hind-paw mechanical withdrawal thresholds, tail-flick and hot-plate latencies. Plasma concentrations of vasoactive neurotransmitters were determined using rat-specific ELISA kits from jugular vein, including calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating polypeptide (PACAP), nitric oxide (NO), and endothelin-1 (ET-1). The result suggested that EA significantly ameliorated the mechanical and thermal hyperalgesia, reduced c-Fos levels in the trigeminal ganglion, and attenuated plasma and dural levels of vasoactive neurotransmitters, especially in the multiple acupuncture points group (GB20+GB34). In conclusion, EA exerts antihyperalgesic effect in a rat model of conscious recurrent migraine, possibly via modulation of the vasoactive neurotransmitters. Furthermore, targeting multiple acupuncture points is more effective than targeting a single point in reducing hyperalgesia.

Craniotomy

This chapter discusses postcraniotomy headache (PCH), a common yet frequently underdiagnosed and undertreated occurrence, with up to 30% of patients experiencing persistent headache after surgery. The chapter identifies risk factors for the development of acute and persistent PCH and describes mechanisms for its development, such as injury to the sensory nerves supplying the scalp and underlying tissues or to the perivascular nerves that supply sensation to the dura mater. Pain management following craniotomy is a balancing act of achieving adequate analgesia while avoiding oversedation, respiratory depression, hypercapnia, nausea, vomiting, and hypertension. Current evidence suggests that a balanced, multimodal approach to the treatment of acute PCH is often required to optimize pain control, minimize undesired side effects, and prevent the development of persistent PCH.