Cleoper C Paule

Publications (8)15.51 Total impact

• Article: Severe burn injury induces a characteristic activation of extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons.

  John P M White, Chin Wing Ko, Antonio Rei Fidalgo, Mario Cibelli, Cleoper C Paule, Peter J Anderson, Celia Cruz, Szabolcs Gomba, Klara Matesz, Gabor Veress, Antonio Avelino, Istvan Nagy
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  ABSTRACT: We have studied scalding-type burn injury-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the spinal dorsal horn, which is a recognised marker for spinal nociceptive processing. At 5min after severe scalding injury to mouse hind-paw, a substantial number of phosphorylated ERK1/2 (pERK1/2) immunopositive neurons were found in the ipsilateral dorsal horn. At 1h post-injury, the number of pERK1/2-labelled neurons remained substantially the same. However, at 3h post-injury, a further increase in the number of labelled neurons was found on the ipsilateral side, while a remarkable increase in the number of labelled neurons on the contralateral side resulted in there being no significant difference between the extent of the labelling on both sides. By 6h post-injury, the number of labelled neurons was reduced on both sides without there being significant difference between the two sides. A similar pattern of severe scalding injury-induced activation of ERK1/2 in spinal dorsal horn neurons over the same time-course was found in mice which lacked the transient receptor potential type 1 receptor (TRPV1) except that the extent to which ERK1/2 was activated in the ipsilateral dorsal horn at 5 min post-injury was significantly greater in wild-type animals when compared to TRPV1 null animals. This difference in activation of ERK1/2 in spinal dorsal horn neurons was abolished within 1h after injury, demonstrating that TRPV1 is not essential for the maintenance of ongoing spinal nociceptive processing in inflammatory pain conditions in mouse resulting from at least certain types of severe burn injury.
  European journal of pain (London, England) 03/2011; 15(7):683-90. · 3.37 Impact Factor
• Article: Xenon reduces activation of transient receptor potential vanilloid type 1 (TRPV1) in rat dorsal root ganglion cells and in human TRPV1-expressing HEK293 cells.

  John P M White, Guy Calcott, Agnes Jenes, Mahmuda Hossein, Cleoper C Paule, Peter Santha, John B Davis, Daqing Ma, Andrew S C Rice, Istvan Nagy
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  ABSTRACT: Xenon provides effective analgesia in several pain states at sub-anaesthetic doses. Our aim was to examine whether xenon may mediate its analgesic effect, in part, through reducing the activity of transient receptor potential vanilloid type 1 (TRPV1), a receptor known to be involved in certain inflammatory pain conditions. We studied the effect of xenon on capsaicin-evoked cobalt uptake in rat cultured primary sensory neurons and in human TRPV1 (hTRPV1)-expressing human embryonic kidney 293 (HEK293) cells. We also examined xenon's effect on the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the rat spinal dorsal horn evoked by hind-paw injection of capsaicin. Xenon (75%) reduced the number of primary sensory neurons responding to the TRPV1 agonist, capsaicin (100 nM-1 μM) by ~25% to ~50%. Xenon reduced the number of heterologously-expressed hTRPV1 activated by 300 nM capsaicin by ~50%. Xenon (80%) reduced by ~40% the number of phosphorylated ERK1/2-expressing neurons in rat spinal dorsal horn resulting from hind-paw capsaicin injection. Xenon substantially reduces the activity of TRPV1 in response to noxious stimulation by the specific TRPV1 agonist, capsaicin, suggesting a possible role for xenon as an adjunct analgesic where hTRPV1 is an active contributor to the excitation of primary afferents which initiates the pain sensation.
  Life sciences 11/2010; 88(3-4):141-9. · 2.56 Impact Factor
• Article: Effects of cannabinoids on capsaicin receptor activity following exposure of primary sensory neurons to inflammatory mediators.

  Neil D Soneji, Cleoper C Paule, Marta Mlynarczyk, Istvan Nagy
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  ABSTRACT: Activation of the cannabinoid 1 (CB1) receptor in cultured primary sensory neurons reduces responses mediated through the transient receptor potential vanilloid type 1 receptor (TRPV1), which plays a pivotal role in the development of heat hyperalgesia and visceral hyper-reflexia in inflammatory conditions. Here, we studied the effect of cannabinoid-evoked inhibitory effect on TRPV1 in inflammatory conditions. The effect of anandamide (1 nM-30 nM) and 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol (HU210; 1 microM-10 microM) was assessed on capsaicin (10 nM or 100 nM)-evoked cobalt uptake in rat cultured primary sensory neurons following the incubation of the cells in an "inflammatory environment" created by the major inflammatory mediators, bradykinin (5 microM), prostaglandin E(2) (5 microM) and nerve growth factor (100 ng/ml) for 10 min. 1 nM and 10 nM anandamide significantly reduced the 10 nM but not the 100 nM capsaicin-evoked responses. HU210 did not produce a significant change in responses evoked by capsaicin at either of its concentrations. The anandamide-induced inhibitory effect could not be reversed by the CB1 receptor antagonist, rimonabant (200 nM) or the membrane-permeable cAMP analogue, 8Br-cAMP (100 microM). These findings suggest that anandamide may inhibit TRPV1-mediated responses in a non-CB1/non-cannabinoid 2 receptor-dependent manner in primary sensory neurons in inflammatory conditions.
  Life sciences 07/2010; 87(5-6):162-8. · 2.56 Impact Factor
• Article: Role of Transient Receptor Potential and Acid-sensing Ion Channels in Peripheral Inflammatory Pain

  John P. M. White, Mario Cibelli, Antonio Rei Fidalgo, Cleoper C. Paule, Faruq Noormohamed, Laszlo Urban, Mervyn Maze, Istvan Nagy
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  ABSTRACT: Pain originating in inflammation is the most common pathologic pain condition encountered by the anesthesiologist whether in the context of surgery, its aftermath, or in the practice of pain medicine. Inflammatory agents, released as components of the body's response to peripheral tissue damage or disease, are now known to be collectively capable of activating transient receptor potential vanilloid type 1, transient receptor potential vanilloid type 4, transient receptor potential ankyrin type 1, and acid-sensing ion channels, whereas individual agents may activate only certain of these ion channels. These ionotropic receptors serve many physiologic functions—as, indeed, do many of the inflammagens released in the inflammatory process. Here, we introduce the reader to the role of these ionotropic receptors in mediating peripheral pain in response to inflammation.
  Anesthesiology 02/2010; 112(3):729-741. · 5.36 Impact Factor
• Article: Cystitis is associated with TRPV1b-downregulation in rat dorsal root ganglia.

  Ana Charrua, Carlos Reguenga, Cleoper C Paule, Istvan Nagy, Francisco Cruz, António Avelino
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  ABSTRACT: The recently identified splice variant of the transient receptor vanilloid type 1 (TRPV1) molecule, TRPV1b, produces a negative-dominant effect on the responsiveness of the TRPV1 channel, which is increased by peripheral inflammatory processes. Here, we studied, using real-time polymerase chain reaction, whether cyclophosphamide injection-evoked cystitis is associated with altered TRPV1/TRPV1b expression in the L5-L6 dorsal root ganglia, which innervate the urinary bladder. We found that while TRPV1 mRNA expression was unchanged, the amount of TRPV1b transcript was significantly reduced in L5-L6 dorsal root ganglia during cystitis. These data indicate that peripheral inflammatory events induce changes in TRPV1b expression in primary sensory neurons, which may result in increased responsiveness of the TRPV1 channel.
  Neuroreport 11/2008; 19(15):1469-72. · 1.66 Impact Factor
• Source

  Available from: cingulate.ibms.sinica.edu.tw

  Chapter: An Historical Introduction to the Endocannabinoid and Endovanilloid Systems

  Istvan Nagy, John P. M. White, Cleoper C. Paule, Attila Köfalvi
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  ABSTRACT: Cannabis and chili pepper have been used for medical, gastronomical and recreational purposes for at least 8,000 years. Nevertheless, it was discovered only eight years ago that the cloned neuronal targets of their active principles, delta9-tetrahydrocannabinol (Δ9-THC) and capsaicin are related to each other, as they all can be activated by some arachidonic acid-derivative endogenous ligands. Here, we will summarize the history of man's relationship with cannabis and capsaicin, and we will detail the most important scientific keystones in the evolution of cannabinoid and vanilloid research, featuring the list of cannabinoid and capsaicin effects, the discovery of endogenous ligands and the cloning of receptors, namely, the CB1 and the CB2 cannabinoid receptor as well as the TRPV1 vanilloid receptor, where the endogenous and the plant-derived substances act upon. This chapter serves, therefore, as an introduction to Cannabinoids and the Brain, the book which will extensively describe the neuronal and, to some extent, the peripheral cannabinoid and vanilloid systems in molecular, pharmacological, physiological, pathological and neuropsychiatric viewpoints.
  12/2007: pages 3-13;
• Source

  Available from: Laszlo Urban

  Chapter: Functional Molecular Biology of the TRPV1 Ion Channel

  Istvan Nagy, John P. M. White, Cleoper C. Paule, Mervyn Maze, Laszlo Urban
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  ABSTRACT: This chapter offers an introduction to the structure and function of TRPV1 receptor. In terms of activators and sites of interaction, we elaborate at least five mechanisms by which TRPV1 receptor may be activated, including ligand binding, protonation, post-translational changes, thermal energy, and electrical energy. The sub-cellular expression of TRPV1 receptor and its expression in primary sensory neurons in the central nervous system and by non-neuronal cells are also examined, as is co-expression of TRPV1 receptor with the cannabinoid 1 receptor. The cellular responses to TRPV1 receptor activation are discussed, including its role in generating ionic influx into primary sensory neurons and desensitisation of TRPV1 receptor. Finally, consideration is afforded to the role of TRPV1 receptor in physiological and pathological conditions.
  12/2007: pages 101-130;
• Article: Molecular Mechanisms of TRPV1-Mediated Pain

  Istvan Nagy, Cleoper C. Paule, John P.M. White
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  ABSTRACT: The transient receptor potential vanilloid type 1 receptor ion channel (TRPV1) (formerly known as the “capsaicin receptor”) plays a crucial role in the excitation of the large subpopulation of nociceptive primary sensory neurons which are sensitive to noxious heat and to a large variety of other pain-inducing stimuli. These ion channels are the important principal mediators of the pain sensations associated with peripheral inflammation which is by far the most important source of pathological pain in humans. Since the cloning of TRPV1, numerous investigations have resulted in the accumulation of substantial amounts of data concerning this ion channel’s molecular, biophysical, and pharmacological properties. Moreover, the mechanisms through which TRPV1 activity may initiate the perception of pain are also beginning to be elucidated. This chapter offers a summary of developments in the rapidly evolving field of TRPV1 research, and considers how TRPV1 activity may contribute to the development of various acute and chronic pain sensations.
  NeuroImmune Biology.