Search results for "Neuropathic pain"
showing 10 items of 115 documents
Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors
2007
Although endocannabinoids constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting from the central actions of cannabinoids. We deleted the type 1 cannabinoid receptor (CB1) specifically in nociceptive neurons localized in the peripheral nervous system of mice, preserving its expression in the CNS, and analyzed these genetically modified mice in preclinical models of inflammatory and neuropathic pain. The nociceptor-spec…
Multiple mechanisms of secondary hyperalgesia
2000
Publisher Summary This chapter discusses the multiple mechanisms of secondary hyperalgesia. The chapter defines the minimal conditions of complexity that must be fulfilled by a model of plasticity of spinal nociceptive transmission in order to explain clinical and psychophysical observations in humans. Secondary hyperalgesia is characterized by a leftward shift of the stimulus-response function for noxious mechanical stimuli. In order to define the afferent pathways involved in inducing central sensitization and in mediating the hyperalgesia to noxious mechanical stimuli, several psychophysical experiments using selective nerve block techniques is performed. Secondary hyperalgesia is likely…
Chapter 33 Experimental human models of neuropathic pain
2006
Publisher Summary This chapter reviews human surrogate models of neuropathic pain that focus on the mechanisms of symptom generation. A vast array of human surrogate models exists for ongoing symptoms, for positive sensory symptoms, and for sensory loss. The chapter discusses that by design, human surrogate models of neuropathic pain involve a reversible modulation of the properties of the nociceptive system such as its acute plasticity (phase 2). They usually do not create a long-lasting and potentially irreversible modification (phase 3). The denervation and ectopic activity of phase 3 can be modeled to a certain extent by transient nerve compression–ischemia and by topical capsaicin. By …
Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy
2021
Abstract Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α1-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α1-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α1-AR expression and activation with spontaneous and sympathetically maintained pain (SMP) induced by intradermal injection of the α1-agonist phenylephrine was investigated. For control purposes the α2-agonist clonidine was injected in a different session. We found that dermal nerve density wa…
Skin innervation at different depths correlates with small fibre function but not with pain in neuropathic pain patients
2012
Background: Neuropathy can lead not only to impaired function but also to sensory sensitization. We aimed to link reduced skin nerve fibre density in different levels to layer-specific functional impairment in neuropathic pain patients and tried to identify pain-specific functional and structural markers. Methods: In 12 healthy controls and 36 patients with neuropathic pain, we assessed clinical characteristics, thermal thresholds (quantitative sensory testing) and electrically induced pain and axon reflex erythema. At the most painful sites and at intra-individual control sites, skin biopsies were taken and innervation densities in the different skin layers were assessed. Moreover, neurona…
Histone post-translational modifications as potential therapeutic targets for pain management
2021
Effective pharmacological management of pain associated with tissue pathology is an unmet medical need. Transcriptional modifications in nociceptive pathways are pivotal for the development and the maintenance of pain associated with tissue damage. Accumulating evidence has shown the importance of the epigenetic control of transcription in nociceptive pathways via histone post-translational modifications (PTMs). Hence, histone PTMs could be targets for novel effective analgesics. Here, we discuss the current understanding of histone PTMs in the modulation of gene expression affecting nociception and pain phenotypes following tissue injury. We also provide a critical view of the translationa…
The craniofacial necrotizing fasciitis after a minor trauma in an elderly white woman
2014
The term necrotizing fasciitis /NF/ was probably first described by Jones in 1871 as “hospital gangrene”. NF, with its fast spreading from the local infection to massive necrosis of the underlying tissues, ie. superficial fascia and subcutaneous layers, is a potentially fatal disease, unless diagnosed early and properly treated. NF is more frequent in frail patients with chronic debilitating illnesses, immune deficiencies or from a poor social background. Sixty percent of NF cases occur in females. Here we present a case of necrotizing fasciitis of the head and neck region after a minor trauma (phenol blocks due to severe neuropathic pain) in an 82-year-old female with the history of trigem…
DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain.
2022
While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summar…
Antihyperalgesic and analgesic properties of the N-methyl-d-aspartate (NMDA) receptor antagonist neramexane in a human surrogate model of neurogenic …
2006
Abstract NMDA-receptors are a major target in the prevention and treatment of hyperalgesic pain states in neuropathic pain. However, previous studies revealed equivocal results depending on study design and efficacy parameters. We tested the analgesic (generalized reduction of generation and processing of nociceptive signalling) and anti-hyperalgesic (prevention of central sensitization) properties of the NMDA-receptor antagonist neramexane and the potassium channel opener flupirtine in the intradermal capsaicin injection model. Furthermore, we tested the effect on pain summation (wind up). Eighteen healthy subjects received either a single dose of neramexane (40 mg p.o.), flupirtine (100 m…
Remote Photoplethysmography for Evaluation of Cutaneous Sensory Nerve Fiber Function
2021
About 2% of the world’s population suffers from small nerve fiber dysfunction, neuropathy, which can result in severe pain. This condition is caused by damage to the small nerve fibers and its assessment is challenging, due to the lack of simple and objective diagnostic techniques. The present study aimed to develop a contactless photoplethysmography system using simple instrumentation, for objective and non-invasive assessment of small cutaneous sensory nerve fiber function. The approach is based on the use of contactless photoplethysmography for the characterization of skin flowmotions and topical heating evoked vasomotor responses. The feasibility of the technique was evaluated on volunt…