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Mechanisms of Pain
Published in Benjamin Apichai, Chinese Medicine for Lower Body Pain, 2021
There are two main types of nociceptor: A-fibers are thinly myelinated and associated with fast conduction and response, such as first acute pain and heat.C-fibers are unmyelinated and associated with longer-lasting and dull pain such as reactions to chemicals and thermal and mechanical stimuli.1
Physiology of the Pain System
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Nociception is carried on primary afferent fibers by Aδ fibers or C fibers. Aδ-fibers are smaller in diameter and thinly myelinated, making them slower conducting (4–30 m/sec) than Aβ-fibers but much quicker than C-fibers.2 Aδ fibers are mechanoreceptors or thermoreceptors that respond to either low- or high-threshold stimuli. Aδ fibers are small, myelinated, and fast conducting. Myelinated axons usually contain specialized terminals that are sensitive to mechanical distortion.1 C-fibers are the smallest fibers and non-myelinated, making them the slowest conducting fiber type (2.5 m/sec).3 These free nerve endings are activated by high-intensity stimuli. C-fibers are polymodal—meaning they respond to mechanical stimuli, thermal stimuli, chemical stimuli, or a combination. Some C-fibers respond only to thermal stimuli. Almost all C-fibers respond to chemical stimuli—specifically capsaicin.4
Pathophysiology and Prevalence of Detrusor-Sphincter Dyssynergia
Published in Jacques Corcos, Gilles Karsenty, Thomas Kessler, David Ginsberg, Essentials of the Adult Neurogenic Bladder, 2020
Marcio Augusto Averbeck, Helmut Madersbacher
As a consequence of an acute SCL, the normal connections between the sacral cord and the supraspinal circuits that control urine storage and release are disrupted. After the so-called “spinal shock phase,” detrusor overactivity (DO) develops. DO is mediated by a spinal micturition reflex that emerges in response to a reorganization of synaptic connections in the spinal cord.2 Bladder afferents that are normally unresponsive to low intravesical pressures become more mechanosensitive, leading to DO. A newly developed spinal reflex circuit, which is mediated by C fibers as a response to a reorganization of synaptic connections in the spinal cord, is thought to be responsible for the development of DO in response to low-volume filling after SCL. In normal micturition, the afferent reflex is carried by Aδ-nerve fibers to dorsal root ganglia. The unmyelinated C fibers are silent under normal conditions. In neurogenic DO, this changes, and transmission is via unmyelinated C fibers, which leads to a shorter latency period.16–18 C fiber–mediated reflexes may be relevant for future studies on new drugs. In complete suprasacral SCL (neurologically defined as ASIA A), there is no modulation of pelvic floor reflexes, such as the pudendo-anal (or urethral) reflex, whereas in incomplete injuries the reflex activity is variably facilitated. DO is therefore often accompanied by DSD.
Mechanisms of action of vitamin B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) in pain: a narrative review
Published in Nutritional Neuroscience, 2023
A. M. Paez-Hurtado, C. A. Calderon-Ospina, M. O. Nava-Mesa
There is evidence of the role of the NO/cyclic guanosine monophosphate (cGMP) in hyperalgesia and allodynia phenomena at the spinal cord level in several models of pain [113]. Modulation of this intracellular cascade has antinociceptive effects after stimulation of type C fibers in inflammatory pain in rats [114]. Considering that the B-complex vitamins regulate the activity of NO/cGMP pathway at levels of tissue GMP [15], an antiallodynic effect of these vitamins through this mechanism is feasible. Indeed, it has been found that different B vitamins (in particular pyridoxine) have antinociceptive effects mediated by activation of guanylyl cyclase in visceral pain models (writhing test) [115], and this mechanism has been also suggested on inflammatory pain [116]. Accordingly, several studies have reported that activation of guanylyl cyclase with the subsequent increase in cGMP may lead to antinociception [12,68,79,117,118]. In addition, cGMP–protein kinase G (PKG) signaling pathway also contributes to modulate hyperexcitability states in compression models of DRG neurons [119]. Song et al. (2003) investigated the possible involvement of cGMP–PKG pathway in inhibition of hyperalgesia in rats with chronic compression of DRG after treatment with thiamine. In that study, intrathecal administration of thiamine inhibited thermal hyperalgesia through activation of cGMP–PKG and potassium channels [118].
Diagnosis and treatment of non-allergic rhinitis: focus on immunologic mechanisms
Published in Expert Review of Clinical Immunology, 2021
Yifan Meng, Chengshuo Wang, Luo Zhang
Neurogenic mechanisms associated with sensory system have also been widely studied; with indirect evidence suggesting C-fibers to play a vital role in the pathophysiology of VMR. C-fibers are unmyelinated fibers of sensory neurons that originate from ethmoidal and posterior nerves and control epithelial, vascular, and glandular processes within the nasal mucosa [59]. C-fibers release neuropeptides like SP and CGRP, and cause a localized increase in vascular permeability and nasal secretion [59]. Indeed, some studies have demonstrated that exposure to nonallergic environmental irritants can trigger the sensory nerve endings and synapsing in the airway epithelial cells and activate transient receptor potential (TRP) channels to release neuropeptides like SP and CGRP though local axonal and centrally mediated reflex, which results in dilatation of submucosal blood vessels and increase of epithelial permeability [47,60]. Indeed, one study has indicated that protein kinase C/protein kinase A (PKC/PKA) mediates phosphorylation of the TRPV1 ion channel leading to influx of calcium into sensory neurons [61]. Thus, based on these findings, altering the expression or activity of the TRP channels may be a potential treatment option for VMR [61].
Clinical diagnosis and management of small fiber neuropathy: an update on best practice
Published in Expert Review of Neurotherapeutics, 2020
Grazia Devigili, Daniele Cazzato, Giuseppe Lauria
Microneurography is a valuable neurophysiological technique developed to record the activity of single C-nociceptors, thermoceptors, mechanoreceptors, and sympathetic fibers from peripheral nerves in awake subjects. This technique provided data regarding the physiological activity of C fiber and elucidated the pathophysiological correlates of clinical phenomena in painful syndromes such as spontaneous activity, sensitization, and hyperexcitability [94]. In SFN and other conditions characterized by peripheral neuropathic pain, microneurography could detect abnormal C-nociceptor activity [20]. Furthermore, it allowed investigating the effect of drugs on blocking the abnormal on-going activity of C-nociceptors [95]. Its application in clinical practice, however, remains partly limited by complex technical requirements, time to perform the exam, and collaboration of the patient.