• Individual sensory neurons can be tuned to many stimuli, each driving unique, stimulus-relevant behaviors, and the ability of multimodal nociceptor neurons to discriminate between potentially harmful and innocuous stimuli is broadly important for organismal survival. (elifesciences.org)
  • Hyperalgesia is an exaggerated and prolonged response to noxious stimuli that can be produced by plasticity at peripheral sites (eg, reduced threshold and/or amplified nociceptor response to noxious stimuli) and centrally in the spinal cord or brain. (nature.com)
  • Those peripheral receptors are called nociceptors , and they can be classified according to how they respond to intense mechanical, thermal, or chemical stimuli. (nationalacademies.org)
  • The most extensively studied nociceptors are the ones that have myelinated axons and respond only to intense mechanical or mechanical and thermal stimuli and the so-called polymodal nociceptors, which have unmyelinated axons and respond to mechanical, thermal, and chemical stimuli. (nationalacademies.org)
  • The myelinated nociceptors appear to encode signals related to pricking first-pain sensations produced by noxious mechanical or thermal stimuli. (nationalacademies.org)
  • After repeated exposure to noxious heat stimuli, nociceptors exhibit lower thresholds, increased sensitivity to stimuli that exceed their thresholds, and spontaneous activity. (nationalacademies.org)
  • Hyperalgesia results in enhancement of spontaneous pain via a reduction in pain threshold and a lengthening in duration of nociceptor response to stimuli. (pharmacology2000.com)
  • Central sensitization, in short, is a hypersensitivity to stimuli from things that are not typically painful. (briomd.com)
  • Patients who find themselves suffering from forms of central sensitization experience pain from stimuli that should not induce pain. (briomd.com)
  • Nociceptors are sensory receptors that respond to painful stimuli. (briomd.com)
  • Nociceptors are sensory nerves that respond to stimuli which produce pain. (rush.edu)
  • We also evidence that CIII neurons make use of atypical depolarizing chloride currents to encode cold, and that overexpression of ncc69 -a fly homologue of NKCC1 -results in phenotypes consistent with neuropathic sensitization, including behavioral sensitization and neuronal hyperexcitability, making Drosophila CIII neurons a candidate system for future studies of the basic mechanisms underlying neuropathic pain. (elifesciences.org)
  • Inflammatory mediators not only activate "pain-"sensing neurons, the nociceptors, to trigger acute pain sensations, more important, they increase nociceptor responsiveness to produce inflammatory hyperalgesia. (jneurosci.org)
  • Central sensitization is a process whereby nociceptive neurons and circuits exhibit increased function in response to activity, inflammation, or injury through a variety of processes that include changes in receptor field size, increases in neuronal excitability, increases in synaptic efficiency/coupling, and changes in neuronal connectivity ( Latremoliere and Woolf, 2009 ). (nature.com)
  • Following brief irradiation of Drosophila larvae with UV, nociceptive sensitization occurs in class IV multiple dendritic (mdIV) neurons, which are polymodal sensory nociceptors. (biomedcentral.com)
  • Diverse signaling pathways have been identified that mediate nociceptive sensitization in mdIV neurons, including TNF, Hedgehog, BMP, and Tachykinin, yet the underlying mechanisms are not completely understood. (biomedcentral.com)
  • Employing the ppk - Gal4 line, which is exclusively expressed in mdIV neurons, we further show that silencing duox in mdIV neurons attenuates UV-induced sensitization. (biomedcentral.com)
  • Our findings reveal a novel role for duox in nociceptive sensitization of Drosophila larvae, and will enhance our understanding of the mechanisms underlying this process in Drosophila sensory neurons. (biomedcentral.com)
  • Next to their acute nociceptive response, mdIV neurons accomplish nociceptive sensitization in response to brief ultraviolet-induced tissue damage in the larval skin [ 11 ]. (biomedcentral.com)
  • Like in mammals, tumor necrosis factor (TNF) signaling was shown to operate in mdIV neurons for nociceptive sensitization [ 11 ]. (biomedcentral.com)
  • Here we report the genetic analysis of ROS-generating Dual Oxidase (Duox) enzymes and find that Duox is required to mediate nociceptive sensitization in mdIV neurons. (biomedcentral.com)
  • Researchers worked off of previous findings regarding the ion channel protein Piezo2 and neurons known as nociceptors. (rush.edu)
  • After a closer look at sensory neurons using single-cell RNA sequencing , investigators also found that Piezo2 is expressed by nociceptors that innervate joints in osteoarthritis in both mice and humans. (rush.edu)
  • MORp constructs designed from promoter regions upstream of the mouse Oprm1 gene (mMORp) were validated for transduction efficiency and selectivity in endogenous MOR+ neurons in the brain, spinal cord, and periphery of mice, with additional studies revealing robust expression in rats, shrews, and human induced pluripotent stem cell (iPSC)-derived nociceptors. (bvsalud.org)
  • Known as tactile allodynia, this sensory distortion is currently viewed as resulting from sensitization of nociceptors that normally don't detect gentle touch and arises as a result of changes in central processing. (nih.gov)
  • Following carrageenan inflammation, there was a marked increase in the proportion of nociceptors which displayed ongoing activity (50% of nociceptors developed spontaneous activity compared to 4% of nociceptors innervating normal uninflamed skin), and this was reflected in a significant increase in the average ongoing discharge activity. (ox.ac.uk)
  • When the NGF-neutralizing molecule trkA-IgG was coadministered with carrageenan at the onset of the inflammation, primary afferent nociceptors did not sensitize and displayed essentially normal response properties, although the inflammation as evidenced by tissue oedema developed normally. (ox.ac.uk)
  • We therefore conclude that NGF is a crucial component for the sensitization of primary afferent nociceptors associated with tissue inflammation. (ox.ac.uk)
  • These products, acting in concert with one another, contribute to inflammation and associated sensitivity and pain, as evidenced by increased vascular permeability, increased leukocyte migration, and increased sensitivity of nociceptors. (nationalacademies.org)
  • Signs of central sensitization: inflammation induced by high demand task occurs in peripheral nerve and spinal cord tissue. (cdc.gov)
  • Prolonged or repeated episodes of inflammation in peripheral tissues that alter nociceptor function is a proposed mechanism of central sensitization implicated in chronic pain. (cdc.gov)
  • The hypothesis that peripheral inflammation is one mechanism of central sensitization is supported by these results. (cdc.gov)
  • At the peripheral nerve and nociceptor level, injury results in inflammation and in activation and over-representation of cation channels, particularly sodium channels. (msdmanuals.com)
  • Additional research in a small number of humans with a rare genetic condition caused by a loss of function of PIEZO2 found that these individuals do not have sensitization and painful reactions to touch after skin inflammation. (nih.gov)
  • Inflammation of the intervertebral disc (IVD) can trigger nerve ingrowth and sensitization. (aofoundation.org)
  • after combined NGF sensitization and UV-B inflammation in humans. (mein-bizeps.de)
  • We found that reducing the amount of Piezo2 expressed by nociceptors could reduce pain in mouse models of osteoarthritis and joint inflammation," Malfait and Miller say. (rush.edu)
  • Here we asked whether NGF contributes to sensitization of primary afferent nociceptors, which are an important component of pain and hyperalgesia in inflamed tissue. (ox.ac.uk)
  • The focus of spatial attention during the induction of central sensitization can modulate the subsequent development of secondary hyperalgesia. (iasp-pain.org)
  • Apart from exciting nociceptors, inflammatory mediators increase nociceptor responsiveness, frequently by initiating G-protein-mediated processes, to cause hyperalgesia. (jneurosci.org)
  • Proinflammatory cytokines, as well as inflammatory mediators such as bradykinins and prostaglandins, play a crucial role in sensitizing nociceptors directly or indirectly through the trigger of various molecular mechanisms that lead to hyperalgesia or hypernociception [ 4 ]. (hindawi.com)
  • Sensitization and hyperalgesia involve the release of various chemical mediators (Hargreaves and Dubner, 1991). (nationalacademies.org)
  • Serotonin, bradykinin, histamine, prostaglandins, substance P (sP) , and various ions (ie, H + or K + )--the biochemical mediators released as a result of tissue injury--have been implicated in nociceptive activation and sensitization (hyperalgesia). (pharmacology2000.com)
  • This continuous painful input induces central sensitization. (medscape.com)
  • The present study used our rat model of upper extremity repetitive motion injury to examine whether mediators of peripheral neuritis contribute to changes in the spinal cord indicative of central sensitization, and whether these changes explain maladaptive behavior. (cdc.gov)
  • We found that performance of the HRHF task induced significant peripheral neuritis that was associated with spinal cord inflammatory markers involved in central sensitization. (cdc.gov)
  • We further compare differences between sensitization resulting from MO and from drug addiction, the neuronal pathways that may be involved, and the genetic susceptibility that may overlap between the two conditions. (biomedcentral.com)
  • In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI. (scienceopen.com)
  • The data indicate that peripheral kainate receptors not only play an important role in normal nociception but also contribute to mechanical sensitivity and heat sensitization accompanying inflammatory pain. (utmb.edu)
  • These findings suggest an important role of peripheral CGRP in visceral nociception and organ cross-sensitization and support the evaluation of CGRP as a therapeutic target for visceral pain in patients with IBS and/or BPS/IC. (aspetjournals.org)
  • By using an in vitro model (with inflamed intervertebral disc cells), the effect of celecoxib on outgrowth and sensitization of dorsal root ganglion cells (DRG), which are the main transmitter of pain signals in the IVD, will be investigated. (aofoundation.org)
  • Treating Discogenic Pain by Reducing Dorsal Root Ganglion Cell Sensitization using the COX-2 Inhibitor Celecoxib - An in vitro Study with Inflammatory Cytokine Treated Annulus Fibrosus Cells. (aofoundation.org)
  • An in vitro skin nerve preparation of the rat was used to directly record the receptive properties of thin myelinated (Adelta) and unmyelinated (C) nociceptors innervating normal hairy skin, carrageenan-inflamed skin and carrageenan-inflamed skin where endogenous NGF had been neutralized by application of a trkA-IgG (tyrosine kinase Aimmunoglobulin G) fusion molecule. (ox.ac.uk)
  • Here, we review the role played by NO on central pain sensitization. (frontiersin.org)
  • This pain sensitization is beneficial to animal survival since it helps to avoid touching damaged tissues until they are healed. (biomedcentral.com)
  • The inhibition of COX-2 by NSAID does not prevent the formation of leukotrienes, which also promote sensitization of nociceptors and result in pain and edema. (bvsalud.org)
  • Using TRPA1-deficient mice, we now show that this channel is the sole target through which mustard oil and garlic activate primary afferent nociceptors to produce inflammatory pain. (scienceopen.com)
  • Thus, TRPA1 is an important component of the transduction machinery through which environmental irritants and endogenous proalgesic agents depolarize nociceptors to elicit inflammatory pain. (scienceopen.com)
  • PGE 1 , PGE 2 , and PGF 2a , are the most potent prostaglandins to produce these sensitization effects. (pharmacology2000.com)
  • In single unit recordings from nociceptors in a glabrous skin-nerve preparation, mechanical sensitization is present in inflamed skin evidenced by a decrease in mechanical threshold and an increase in discharge rate during a suprathreshold, constant force stimulus. (utmb.edu)
  • The administration of TNF- α and interleukins IL-1 β , IL-8, IL-12, IL-15, and IL-18 in rodents via intradermal route has been shown to produce a heightened and prolonged mechanical sensitization and hypernociception [ 5 ]. (hindawi.com)
  • They also found that female mice were protected from mechanical sensitization associated with inflammatory joint pain, and male mice were protected from the joint pain associated with osteoarthritis. (rush.edu)
  • There is a dose-dependent increase in kainate-induced nociceptor activity in both normal and inflamed skin but the kainate required to induce activation is reduced in inflamed skin. (utmb.edu)
  • Intense or sustained activation of peripheral nociceptors can induce central sensitization. (iasp-pain.org)
  • It is postulated that peripheral activation or sensitization of myofascial nociceptors play a major role in episodic TTH. (medscape.com)
  • Treatments target symptoms and include hormonal suppression, surgery or a combination of both approaches, as well as multidisciplinary care to address persistent pain arising from central sensitization and nociplastic pain processes, if required. (cmaj.ca)
  • Exposure of normal and inflamed nociceptors to 0.3mM kainate sensitizes fibers to re-application of kainate and heat. (utmb.edu)
  • Irritable bowel syndrome (IBS) and bladder pain syndrome/interstitial cystitis (BPS/IC) are comorbid visceral pain disorders seen commonly in women with unknown etiology and limited treatment options and can involve visceral organ cross-sensitization. (aspetjournals.org)
  • A handshake, a hug, anything regarding sense of touch can be greatly affected by chronic pain, particularly in those suffering from central sensitization disorders. (briomd.com)
  • In three rodent models, we employed a monoclonal anti-CGRP F(ab') 2 to investigate the hypothesis that visceral organ cross-sensitization is mediated by abnormal CGRP signaling. (aspetjournals.org)
  • Visceral organ cross-sensitization was induced in adult female rats via transurethral infusion of protamine sulfate (PS) into the urinary bladder or infusion into the colon of trinitrobenzene sulfonic acid (TNBS). (aspetjournals.org)
  • This indicates that top-down attentional factors can modulate the development of central sensitization by peripheral nociceptive input, and that the focus of spatial attention, besides its modulatory effects on perception, can affect activity-dependent neuroplasticity. (iasp-pain.org)
  • sensitization-an explanation for spontaneous nociceptor activity? (mein-bizeps.de)
  • Thermal sensitization is also present evidenced by a decrease in heat threshold. (utmb.edu)
  • Although proportions of kainate-activated nociceptors are the same in normal and inflamed skin, the kainate-induced mean discharge rate is significantly enhanced in inflamed skin. (utmb.edu)