Mediating roles of the vanilloid receptor TRPV1 in activation of rat primary afferent nociceptive neurons by formaldehyde

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Author:
TIAN Li-Juan(Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China)
DU Yi-Ru(Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China)
XIAO Yong(Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,the Fourth Military Medical University,Xi'an 710038,China)
LV Zhuo-Min(Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,the Fourth Military Medical University,Xi'an 710038,China)
YU Yao-Qing(Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,the Fourth Military Medical University,Xi'an 710038,China)
CUI Xiu-Yu(Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China)
CHEN Jun(Institute for Biomedical Sciences of Pain,Capital Medical University,Beijing 100069,China;Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders,Tangdu Hospital,the Fourth Military Medical University,Xi'an 710038,China)
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 61, Issue 05, 2009
DOI:
Key Word:
formalin test; nociceptor; TRPV1 receptor; dorsal root ganglion; patch clamp; calcium imaging

Abstract: The formalin test is a commonly used animal model of acute and tonic pain. However, the molecular targets of formaldehyde (FA, the main ingredient of the formalin solution) on primary nociceptor cells remain controversial. In this report, the effects of FA or electrophysiologically-identified primary nociceptor cells were evaluated in vitro and the roles of the vanilloid receptor TRPV 1 in Faproduced activation of primary nociceptors were also examined at both cellular and behavioral levels. Of 92 acutely dissociated dorsaal root ganglion (DRG) cells recorded by current patch-clamp technique, 34% were discharged by FA application with the mean onset latencies of the first action potential (AP) being (367.34±32.96) s. All the FA-sensitive cells were identified as nociceptor cells by their distinguishable features of AP including longer duration, existence of a hump (a shoulder or inflection) on the repolarizing phase, and longer after-hyperpolarization of Aps. Co-application of capsazepine (CPZ), a competitive antagonist of TRPV 1 receptors, could block FA-evoked firing with partial inhibition on the membrane depolarization of all cells tested. Of another 160 cells examined by confocal calcium imaging, 32% were shown to respond to FA with an intracellular Ca~(2+) rise. Of 51 FA-sensitive cells, 67% were suppressed by CPZ, suggesting partial involvement of TRPVI in mediation of the FA-evoked intracellular Ca~(2+) rise. Under voltage. Clamp mode, 41% of DRG cells were evoked to give rise to inward current with the remaining 59% being unchanged. In separate experiments on the other 56 FA-sensitive ceils, concentration-dependent increase in the FA-evoked current amplitude was demonstrated In comparison with controls, the FA-evoked inward current could be significantly suppressed by CPZ that was further enhanced by HC-030031, a TRPA1 selective antagonist. Finally, local effects of CPZ were confirmed in the formalin test and it was shown that the formalin-induced paw flinches were strongly suppressed by CPZ in phase 1 but with phase 2 being significantly suppressed only during 25-55 min. It is therefore concluded that FA can directly activate a subpopulation of primary nociceptor cells and the FA-induced AP discharges are likely to contribute mainly to phase 1, but not phase 2 of the formalin-induced nociception. The activation of primary nociceptor cells by FA is likely to be mediated, at least in part, through TRPV1 and/or TRPA1 receptors.

  • [1]Dubuisson D,Dennis SG.The formalin test:a quantitative study of the analgesic effects of morphine,meperidine,and brain stem stimulation in rats and cats.Pain 1977; 4:161-174.
  • [2]Tjolsen A,Berge OG,Hunskaar S,Rosland JH,Hole K.The formalin test:an evaluation of the method.Pain 1992; 51:5-17.
  • [3]Porto CA,Cavazzuti M.Spatial and temporal aspects of spinal cord and brainstem activation in the formalin pain model.Prog Neurobiol 1993; 41:565-607.
  • [4]Hunskaar S,Hole K.The formalin test in mice:dissociation between inflammatory and non-inflammatory pain.Pain 1987;30:103-114.
  • [5]Dallel R,Raboisson P,Clavelou P,Saade M,Woda A.Evidence for a peripheral origin of the tonic nociceptive response to subcutaneous formalin.Pain 1995; 61:11-16.
  • [6]Chen J,Koyama N,Yokota T.Effects of subcutaneous formalin on responses of dorsal horn wide dynamic range neurons and primary afferent neurons in the cat.Pain Res 1996; 11:71-83.
  • [7]Taylor BK,Peterson MA,Basbaum AI.Persistent cardiovascular and behavioral nociceptive responses to subcutaneous formalin require peripheral nerve input.J Neuroaci 1995; 15:7575-7584.
  • [8]McCall WD,Tanner KD,Levine JD.Formalin induces biphasic activity in C-fibers in the rat.Neurosci Lett 1996; 208:45-48.
  • [9]Puig S,Sorkin LS.Formalin-evoked activity in identified primary afferent fibers:systemic lidoeaine suppresses phase-2 activity.Pain 1996; 64:345-355.
  • [10]Chen J,Koyama N.Effects of subcutaneous formalin on responses of identified primary afferent units in the cat:An electrophysiological study.Chin J Neuroanat (神经解剖学杂志)1996; 12:381-393.
  • [11]MeNamara CR,MandeI-Brehm J,Bautista DM,Siemens J,Deranian KL,Zhao M,Hayward NJ,Chong JA,Julius D,Moran MM,Fanger CM.TRPA1 mediates formalin-induced pain.Proc Natl Acad Sci USA 2007; 104:13525-13530.
  • [12]Macpherson LJ,Xiao B,Kwan KY,Petrus MJ,Dubin AE,Hwang S,Cravatt B,Corey DP,Patapoutian A.An ion channel essential for sensing chemical damage.J Neurosci 2007; 27:11412-11415.
  • [13]Andrade EL,Luiz AP,Ferreira J,Calixto JB.Pronociceptive response elicited by TRPA1 receptor activation in mice.Neuroscience 2008; 152:511-520.
  • [14]Fischer L,Tambeli CH,Parada CA.TRPAl-mediated nociception.Neuroscience 2008; 155:337-338.
  • [15]Parada CA,Tambeli CH,Cunha FQ,Ferreira SH.The major role of peripheral release of histamine and 5-hydroxytryptamine in formalin-induced nociception.Neuroscience 2001; 102:937-944.
  • [16]Reeh P.TRPA1-mediated nociception:response to letter by Fischer et al.Neuroscience 2008; 155(2):339.
  • [17]Cameron AA,Leah JD,Snow PJ.The electrophysiologieal and morphological characteristics of feline dorsal root ganglion cells.Brain Res 1986; 362:1-6.
  • [18]Djouhari L,Bleazard L,Lawson SN.Association of somatic action potential shape with sensory receptive properties in guineapig dorsal root ganglion neurones.J Physiol 1998; 513 (Pt 3):857-872.
  • [19]Koerber HR,Druzinsky RE,Mendell LM.Properties of somata of spinal dorsal root ganglion cells differ according to peripheralreceptor innervated.J Neurophysiol 1988; 60:1584-1596.
  • [20]Fang X,McMullan S,Lawson SN,Djouhri L.Electrophysiological differences between nociceptive and non-nociceptive dorsal root ganglion neurones in the rat in vivo.J Physiol 2005;565:927-943.
  • [21]Kirschstein T,Greffrath W,Busselberg D,Treede RD.Inhibitionof rapid heat responses in nociceptive primary sensory neurons of rats by vanilloid recptor antagonis.J Neurophysiol 1999; 82:2853-2860.
  • [22]Petruska JC,Napapom J,Johnson RD,Gu JG,Cooper BY.Subclassified acutely dissociated cells of rat DRG:histochemistry and patterns of capsaicin-,proton-,and ATP-activatod currents.J Neurophysiol 2000; 84:2365-2379.
  • [23]Julius D,McCleskey EW.Cellular and molecular properties of primary afferent neurons.In:McMahon SB,Koltzenburg M,Ed.Wall and Meizack's Textbook of Pain,5th edition.China:Elsevier Ltd.Churchill Livingstone,2006,35-48.
  • [24]Caterina MJ,Schumacher MA,Tominaga M,Rosen TA,Levine JD,Julius D.The capsaicin receptor:a beat-activated ion channel in the pain pathway.Nature 1997; 389:816-824.
  • [25]Caterina MJ,Rosen TA,Tominaga M,Brake A J,Julius D.A capsaicin-receptor homologne with a high threshold for noxious heat.Nature 1999; 398:436-441.
  • [26]Guo A,Vulchanova L,Wang J,Li X,Elde R.Immunocytochemical localization of the vanilloid receptor 1 (VR1):relationship to neuropeptides,the P2X3 purinoceptor and IB4 binding sites.EurJ Neurosci 1999; 11:946-958.
  • [27]McIntyre P,McLatchie LM,Chambers A,Phillips E,Clarke M,Savidge J,Toms C,Peacock M,Shah K,Winter J,Weerasakera N,Webb M,Rang HP,Bevan S,James IF.Pharmacological differences between the human and rat vanilloid receptor 1 (VR1).Br J Pharmacol 2001; 132:1084-1094.
  • [28]Binzea U,Greffrath W,Hennessy S,Bausen M,Saaler-Reinhardt S,Treede RD.Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV 1 and TRPV2) and the cannabinoid receptor CB 1 in rat dorsal root ganglion neurons.Neuroscience 2006; 142:527-539.
  • [29]Szallasi A,Blumberg PM.Vanilloid (Capsaicin) receptors and mechanisms.Pharmacoi Rev 1999; 51:159-212.
  • [30]Pall ML,Anderson JH.The vanilloid receptor as a putative target of diverse chemicals in multiple chemical sensitivity.Arch Environ Health 2004; 59:363-375.
  • [31]Smart D,Gunthorpe MJ,Jerman JC,Nasir S,Gray J,Muir AI,Chambers JK,Randall AD,Davis JB.The endogenous lipid anandamide is a full agonist at the human vanilloid receptor(hVR1).Br J Pharmacol 2000; 129:227-230.
  • [32]Hwang SW,Cho H,Kwak J,Lee SY,Kang CJ,Jung J,Cho S,Min KH,Suh YG,Kim D,Oh U.Direct activation of capsaicin receptors by products of lipoxygenases:endogenous capsaicin-like substances.Proc Natl Acad Sci USA 2000; 97:6155-6160.
  • [33]Tominaga M,Caterina MJ,Malmberg AB,Rosen TA,Gilbert H,Skinner K,Raumann BE,Basbaum AI,Julius D.The cloned capsaicin receptor integrates multiple pain-producing stimuli.Neuron 1998; 21:531-543.
  • [34]Santos AR,Calixto JB.Ruthenium red and capsazepine antinociceptive effect in formalin and capsaicin models of pain in mice.Neurosci Lett 1997; 235:73-76.
  • [35]Kanai Y,Hara T,Imai A.Participation of the spinal TRPVI receptors in formalin-evoked pain transduction:a study using a selective TRPV1 antagonist,iodo-resiniferatoxin.J Pharm Pharmacol 2006; 58:489-493.
  • [36]Zimmermann M.Ethical guidelines for investigations of experimental pain in couscions animals.Pain 1983; 16:109-110.
  • [37]Seroggs RS,Fox AP.Calcium current variation between acutely isolated adult rat dorsal root ganglion neurons of different size.J Physiol 1992; 445:639-658.
  • [38]Zhang C,Zhou Z.Ca~(2+)-independent but voltage-dependent secretion in mammalian dorsal root ganglion neurons.Nat Neurosci 2002; 5:425-430.
  • [39]Maruo K,Yamamoto H,Yamamoto S,Nagata T,Fujikawa H,Kanno T,Yaguchi T,Maruo S,Yoshiya S,Nishizaki T.Modulation of P2X receptors via adrenergic pathways in rat dorsal root ganglion neurons after sciatic nerve injury.Pain 2006; 120:106-112.
  • [40]Sculptoreanu A,de Groat we.Neurokinins enhance excitability in capsaicin-responsive DRG neurons.Exp Neurol 2007; 205:92-100.
  • [41]Samer RE,Crown ED,Moore EL,Liang HA,Choong KC,Dima S,Henze DA,Kane SA,Urban MO.HC-030031,a TRPA1 selective antagonist,attenuates inflammatory-and neuropathyinduced mechanical hypersensitivity.Mol Pain 2008; 4:48.
  • [42]Chen J,Koyama N.Differential activation of spinal dorsal horn units by subcutaneous formalin injection in the cat:an electrophysiological study.Exp Brain Res 1998; 118:14-18.
  • [43]Chen J,Luo C,Li HL.Thecontribution of spinal neuronal changes to development of prolonged,tonic nociceptive responses of the cat induced by subcutaneous bee venom injection.Eur J Pain 1998; 2:359-376.
  • [44]Chen J,Luo C,Li HL,Chen HS.Primary hyperalgesia to mechanical and heat stimuli following subcutaneous bee venom injection into the plantar surface of hindpaw in the conscious rat:A comparative study with the formalin test.Pain 1999; 83:67-76.
  • [45]Dickenson AH,Knox RJ.Antagonism of mu-opioid receptor-mediated inhibitions of nociceptive neurones by U50488H and dynorphin Al-13 in the rat dorsal horn.Ncurosci Lett 1987; 75:229-234.
  • [46]You HJ,Chen J.Differential effects of subcutaneous injection of formalin and bee venom on responses of wide-dynamic-range neurons in spinal dorsal horn of the rat.Eur J Pain 1999; 3:177-180.
  • [47]Zwick M,Davis BM,Woodbury CA,Burkett JN,Koerber HR,Simpson JF,Albers KM.Glial cell line-derived neurotrophic factor is a survival factor for isolectin B4-positive,but not vanilloid receptor 1-positive,neurons in the mouse.J Neurosci 2002; 22:4057-4065.
  • [48]Story GM,Peier AM,Reeve A J,Eid SR,Mosbacher J,Hricik TR,Earley TJ,He,garden AC,Andersson DA,Hwang SW,McIntyre P,Jegla T,Bevan S,Patapoutian A.ANKTM1,a TRP-like channel expressed in nociceptive neurons,is activated by cold temperatures.Cell 2003; 112:819-829.
  • [49]Reid G.ThermoTRP channels and cold sensing:what are they really up to? Pflugers Arch 2005; 451:250-263.
  • [50]Walpole CS,Bevan S,Bovennann G,Boelsterli JJ,Breckenridge R,Davies JW,Hughes GA,James I,Oberer L,Winter J,Wrigglesworth R.The discovery of capsazepine,the fast competitive antagonist of the sensory neuron excitants capsaicin and resiniferatoxin.J Med Chem 1994; 37:1942-1954.
  • [51]Valenzano K J,Sun Q.Current perspectives on the therapeutic utility of VR 1 antagonists.Curr Med Chem 2004; 11:3185-3202.
  • [52]Szallasi A,Contright DN,Blum CA,Eid SR.The vanilloid receptor TRPV1:10 years from channel cloning to antagonist proof-ofconcept.Nat Rev Drug Discov 2007; 6:357-372.
  • [53]Liu L,Simon SA.Capsazepine,a vanilloid receptor antagonist,inhibits nicotinic acetylcholine receptors in rat trigeminal ganglia.Neurosci Lett 1997; 228:29-32.
  • [54]Docherty RJ,Yeats JC,Piper AS.Capsazepine block of voltageactivated calcium channels in adult rat dorsal root ganglion neurones in culture.Br J Pharmacol 1997; 121:1461-1467.
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