Nociceptors—Noxious Stimulus Detectors

Woolf, Clifford J.; Ma, Qiufu

doi:10.1016/j.neuron.2007.07.016

Cited by 828 publications

(735 citation statements)

References 119 publications

(155 reference statements)

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“…This sensitization, described as increased efficiency of synaptic conduction, is evident in every patient with chronic pain due to changes in the central, as well as the peripheral nervous system [24]. Several chemical irritants, such as cytokines, matrix metalloprotease, fibroblast growth factor, leukotrienes, thromboxanes, prostaglandins, immunoglobulins, among others, known to cause inflammation, are considered to play a role in nociceptor sensitization [37].…”

Section: Discussionmentioning

confidence: 99%

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

2011

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Introduction The symptoms of lumbar disc herniation, such as low back pain and sciatica, have been associated with local release of cytokines following the inflammatory process induced by the contact of the nucleus pulposus (NP) with the spinal nerve. Material and methods Using an animal experimental model of intervertebral disc herniation and behavioral tests to evaluate mechanical (electronic von Frey test) and thermal (Hargreaves Plantar test) hyperalgesia in the hind paw of rats submitted to the surgical model, this study aimed to detect in normal intervertebral disc the cytokines known to be involved in the mechanisms of inflammatory hyperalgesia, to observe if previous exposure of the intervertebral disc tissue to specific antibodies could affect the pain behavior (mechanical and thermal hyperalgesia) induced by the NP, and to observe the influence of the time of contact of the NP with the fifth lumbar dorsal root ganglion (L5-DRG) in the mechanical and thermal hyperalgesia. Results The cytokines present at highest concentrations in the rat NP were TNF-a, IL-1b and CINC-1. Rats submitted to the disc herniation experimental model, in which a NP from the sacrococcygeal region is deposited over the right L5-DRG, showed increased mechanical and thermal hyperalgesia that lasted at least 7 weeks. When the autologous NP was treated with antibodies against the three cytokines found at highest concentrations in the NP (TNF-a, IL-1b and CINC-1), there was decrease in both mechanical and thermal hyperalgesia in different time points, suggesting that each cytokine may be important for the hyperalgesia in different steps of the inflammatory process. The surgical remotion of the NP from herniated rats 1 week after the implantation reduced the hyperalgesia to the level similar to the control group. This reduction in the hyperalgesia was also observed in the group that had the NP removed 3 weeks after the implantation, although the intensity of the hyperalgesia did not decreased totally. The removal of the NP after 5 weeks did not changed the hyperalgesia observed in the hind paw, which suggests that the longer the contact of the NP with the DRG, the greater is the possibility of development of chronic pain. Conclusion Together our results indicate that specific cytokines released during the inflammatory process induced by the herniated intervertebral disc play fundamental role in the development of the two modalities of hyperalgesia (mechanical and thermal) and that the maintenance of this inflammation may be the most important point for the chronification of the pain.

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Section: Discussionmentioning

confidence: 99%

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

2011

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“…We found here that low dose capsaicin, which evokes a near-pure thermal hyperalgesia without C-fiber destruction (27,33), produced much reduced pain perception in the AQP1 Ϫ/Ϫ mice. Remarkable phenotype differences were also found upon challenge with bradykinin and PGE 2 , which are major components of the inflammatory soup and sensitize small DRG neurons through G protein-coupled receptors targeting TTX-R and TRP channels (43). Regarding PGE 2 testing, Shields et al (15) reported no differences for a hypoosmotic challenge in the setting of PGE 2 -induced inflammation.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-1 Tunes Pain Perception by Interaction with Nav1.8 Na+ Channels in Dorsal Root Ganglion Neurons

Zhang

Verkman

2010

Journal of Biological Chemistry

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Aquaporin-1 (AQP1) water channels are expressed in the plasma membrane of dorsal root ganglion (DRG) neurons. We found reduced osmotic water permeability in freshly isolated DRG neurons from AQP1 Aquaporins (AQPs) 2 are water-transporting proteins expressed in epithelial, endothelial, and other cell types. In the central nervous system AQP4 is expressed in glial cells, where it plays a role in cerebral edema (1, 2), glial cell migration (3, 4), and neuroexcitation (5, 6). The mechanisms of AQP4 modulation of seizure dynamics (5), cortical spreading depression (6), vision (7), hearing (8), and olfaction (9) remain unclear. AQP4-dependent Kir4.1 K ϩ channel function has been suggested from delayed K ϩ reuptake from brain extracellular space after neuroexcitation (6, 10); however, patch clamp analysis showed AQP4-independent Kir4.1 K ϩ channel function (11). Extracellular space expansion, which has been found AQP4-deficient brain (12, 13), may contribute to the altered neuroexcitation phenotype. Neurons in the central nervous system do not express AQPs.Water channel AQP1 is abundant in hematopoietic cells and kidney. In normal brain AQP1 expression is restricted to the choroid plexus, where it facilitates the secretion of cerebrospinal fluid (14). In the spinal cord and peripheral nervous system, AQP1 is expressed in sensory neurons in dorsal root ganglia (DRG) that are associated with pain nociception (15-17). These neurons, whose cell bodies reside in the DRG, carry sensory signals from the periphery through small diameter, non-myelinated fibers that synapse in the superficial lamina of the dorsal horn in the spinal cord (18). Two prior studies on pain phenotype in AQP1 Ϫ/Ϫ mice have reported conflicting behavioral findings. Oshio et al. (16) reported mild impairment in pain nociception in AQP1 Ϫ/Ϫ mice after thermal (tail flick) and chemical (capsaicin) stimuli, with no differences in response to mechanical stimuli. Shields et al. (15) confirmed AQP1 expression in DRG neurons and partially colocalization with TRPV1 and substance P; however, they reported no significant differences in behavioral pain tests. The role of AQP1 in neuronal function in the DRG has, thus, remained unclear, as does its role in neurons in trigeminal and nodose ganglia, where it is also expressed.To clarify the role of AQP1 in pain physiology, we did more extensive behavioral testing as well as immunolocalization, water permeability, and patch clamp studies on freshly isolated, dissociated DRG neurons from wild type (AQP1 ϩ/ϩ ) and AQP1 null (AQP1 Ϫ/Ϫ ) mice. We found greatly reduced behavioral response to inflammatory thermal and cold pain in littermatched AQP1 Ϫ/Ϫ mice and distinct electrophysiological defects related to impaired Na v 1.8 Na ϩ channel functioning in AQP1-deficient DRG neurons. Patch clamp, immunoprecipitation, and single particle tracking studies in transfected cell models suggested a novel AQP1-Na v 1.8 interaction as responsible, in part, for the impairment in pain-sensing in AQP1 deficiency. EXPERIMENTAL PROCEDURES...

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“…95), the suppressive influence of innocuous A-fiber mechanosensitive inputs at a systems level (18), and the extrapolation of cellular assays to nociception (e.g., poking, ref. This topic is reviewed in more detail elsewhere (12,19,(91)(92)(93).…”

Section: Transduction Of Noxious Mechanical Stimulimentioning

confidence: 99%

Nociceptors: the sensors of the pain pathway

Dubin

Patapoutian²

2010

J. Clin. Invest.

1,014

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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Nociceptors—Noxious Stimulus Detectors

Cited by 828 publications

References 119 publications

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

Cytokine inhibition and time-related influence of inflammatory stimuli on the hyperalgesia induced by the nucleus pulposus

Aquaporin-1 Tunes Pain Perception by Interaction with Nav1.8 Na+ Channels in Dorsal Root Ganglion Neurons

Nociceptors: the sensors of the pain pathway

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