Inhibition of synaptic transmission by anandamide precursor 20:4-NAPE is mediated by TRPV1 receptors under inflammatory conditions
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic-ecollection
Document type Journal Article
PubMed
37426071
PubMed Central
PMC10325575
DOI
10.3389/fnmol.2023.1188503
Knihovny.cz E-resources
- Keywords
- 20:4-NAPE, CB1, NAPE-PLD, TRPV1, anandamide, inflammation, spinal cord,
- Publication type
- Journal Article MeSH
Transient receptor potential ion channel, vanilloid subfamily, type 1 (TRPV1) cation channel, and cannabinoid receptor 1 (CB1) are essential in the modulation of nociceptive signaling in the spinal cord dorsal horn that underlies different pathological pain states. TRPV1 and CB1 receptors share the endogenous agonist anandamide (AEA), produced from N-arachidonoylphosphatidylethanolamine (20:4-NAPE). We investigated the effect of the anandamide precursor 20:4-NAPE on synaptic activity in naive and inflammatory conditions. Patch-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) from superficial dorsal horn neurons in rat acute spinal cord slices were used. Peripheral inflammation was induced by subcutaneous injection of carrageenan. Under naive conditions, mEPSCs frequency (0.96 ± 0.11 Hz) was significantly decreased after 20 μM 20:4-NAPE application (55.3 ± 7.4%). This 20:4-NAPE-induced inhibition was blocked by anandamide-synthesizing enzyme N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor LEI-401. In addition, the inhibition was prevented by the CB1 receptor antagonist PF 514273 (0.2 μM) but not by the TRPV1 receptor antagonist SB 366791 (10 μM). Under inflammatory conditions, 20:4-NAPE (20 μM) also exhibited a significant inhibitory effect (74.5 ± 8.9%) on the mEPSCs frequency that was prevented by the TRPV1 receptor antagonist SB 366791 but not by PF 514273 application. Our results show that 20:4-NAPE application has a significant modulatory effect on spinal cord nociceptive signaling that is mediated by both TRPV1 and CB1 presynaptic receptors, whereas peripheral inflammation changes the underlying mechanism. The switch between TRPV1 and CB1 receptor activation by the AEA precursor 20:4-NAPE during inflammation may play an important role in nociceptive processing, hence the development of pathological pain.
Department of Physiology University of Debrecen Debrecen Hungary
Laboratory of Pain Research Institute of Physiology of the Czech Academy of Sciences Prague Czechia
See more in PubMed
Adamek P., Heles M., Palecek J. (2019). Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy. Neuropharmacology 146, 163–174. doi: 10.1016/j.neuropharm.2018.11.027, PMID: PubMed DOI
Ahluwalia J., Urban L., Bevan S., Nagy I. (2003). Anandamide regulates neuropeptide release from capsaicin-sensitive primary sensory neurons by activating both the cannabinoid 1 receptor and the vanilloid receptor 1 in vitro. Eur. J. Neurosci. 17, 2611–2618. doi: 10.1046/j.1460-9568.2003.02703.x, PMID: PubMed DOI
Ahluwalia J., Urban L., Capogna M., Bevan S., Nagy I. (2000). Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons. Neuroscience 100, 685–688. doi: 10.1016/S0306-4522(00)00389-4 PubMed DOI
Amaya F., Shimosato G., Kawasaki Y., Hashimoto S., Tanaka Y., Ji R. R., et al. . (2006). Induction of CB1 cannabinoid receptor by inflammation in primary afferent neurons facilitates antihyperalgesic effect of peripheral CB1 agonist. Pain 124, 175–183. doi: 10.1016/j.pain.2006.04.001, PMID: PubMed DOI
Baccei M. L., Bardoni R., Fitzgerald M. (2003). Development of nociceptive synaptic inputs to the neonatal rat dorsal horn: glutamate release by capsaicin and menthol. J. Physiol. 549, 231–242. doi: 10.1113/jphysiol.2003.040451, PMID: PubMed DOI PMC
Bari M., Oddi S., De Simone C., Spagnolo P., Gasperi V., Battista N., et al. . (2008). Type-1 cannabinoid receptors colocalize with caveolin-1 in neuronal cells. Neuropharmacology 54, 45–50. doi: 10.1016/j.neuropharm.2007.06.030, PMID: PubMed DOI PMC
Binzen U., Greffrath W., Hennessy S., Bausen M., Saaler-Reinhardt S., Treede R. D. (2006). Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons. Neuroscience 142, 527–539. doi: 10.1016/j.neuroscience.2006.06.020, PMID: PubMed DOI
Chen J., Varga A., Selvarajah S., Jenes A., Dienes B., Sousa-Valente J., et al. . (2016). Spatial distribution of the cannabinoid type 1 and capsaicin receptors may contribute to the complexity of their crosstalk. Sci. Rep. 6:33307. doi: 10.1038/srep33307, PMID: PubMed DOI PMC
Comunanza V., Carbone E., Marcantoni A., Sher E., Ursu D. (2011). Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons. Pflugers Arch. 462, 709–722. doi: 10.1007/s00424-011-1023-5, PMID: PubMed DOI
Di Scala C., Fantini J., Yahi N., Barrantes F. J., Chahinian H. (2018). Anandamide revisited: how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter. Biomol. Ther. 8:20031. doi: 10.3390/biom8020031, PMID: PubMed DOI PMC
Dow R. L., Carpino P. A., Hadcock J. R., Black S. C., Iredale P. A., DaSilva-Jardine P., et al. . (2009). Discovery of 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyraz olo[3,4-f][1,4]oxazepin-8(5H)-one (PF-514273), a novel, bicyclic lactam-based cannabinoid-1 receptor antagonist for the treatment of obesity. J. Med. Chem. 52, 2652–2655. doi: 10.1021/jm900255t, PMID: PubMed DOI
Ermolyuk Y. S., Alder F. G., Surges R., Pavlov I. Y., Timofeeva Y., Kullmann D. M., et al. . (2013). Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels. Nat. Neurosci. 16, 1754–1763. doi: 10.1038/nn.3563, PMID: PubMed DOI PMC
Farquhar-Smith W. P., Egertova M., Bradbury E. J., McMahon S. B., Rice A. S., Elphick M. R. (2000). Cannabinoid CB(1) receptor expression in rat spinal cord. Mol. Cell. Neurosci. 15, 510–521. doi: 10.1006/mcne.2000.0844 PubMed DOI
Goncalves Dos Santos G., Li R., Ng M. P. E., Lemes J. B. P., Vieira W. F., Nagy I., et al. . (2020). CB1 receptor-dependent desensitisation of TRPV1 channels contributes to the analgesic effect of dipyrone in sensitised primary sensory neurons. Br. J. Pharmacol. 177, 4615–4626. doi: 10.1111/bph.15170, PMID: PubMed DOI PMC
Gunthorpe M. J., Rami H. K., Jerman J. C., Smart D., Gill C. H., Soffin E. M., et al. . (2004). Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist. Neuropharmacology 46, 133–149. doi: 10.1016/S0028-3908(03)00305-8, PMID: PubMed DOI
Hegyi Z., Hollo K., Kis G., Mackie K., Antal M. (2012). Differential distribution of diacylglycerol lipase-alpha and N-acylphosphatidylethanolamine-specific phospholipase d immunoreactivity in the superficial spinal dorsal horn of rats. Glia 60, 1316–1329. doi: 10.1002/glia.22351, PMID: PubMed DOI PMC
Hegyi Z., Kis G., Hollo K., Ledent C., Antal M. (2009). Neuronal and glial localization of the cannabinoid-1 receptor in the superficial spinal dorsal horn of the rodent spinal cord. Eur. J. Neurosci. 30, 251–262. doi: 10.1111/j.1460-9568.2009.06816.x, PMID: PubMed DOI
Heles M., Mrozkova P., Sulcova D., Adamek P., Spicarova D., Palecek J. (2021). Chemokine CCL2 prevents opioid-induced inhibition of nociceptive synaptic transmission in spinal cord dorsal horn. J. Neuroinflammation 18:279. doi: 10.1186/s12974-021-02335-4, PMID: PubMed DOI PMC
Howlett A. C., Barth F., Bonner T. I., Cabral G., Casellas P., Devane W. A., et al. . (2002). International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev. 54, 161–202. doi: 10.1124/pr.54.2.161, PMID: PubMed DOI
Katona I., Freund T. F. (2008). Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat. Med. 14, 923–930. doi: 10.1038/nm.f.1869, PMID: PubMed DOI
Katona I., Urban G. M., Wallace M., Ledent C., Jung K. M., Piomelli D., et al. . (2006). Molecular composition of the endocannabinoid system at glutamatergic synapses. J. Neurosci. 26, 5628–5637. doi: 10.1523/JNEUROSCI.0309-06.2006, PMID: PubMed DOI PMC
Kim C., Jun K., Lee T., Kim S. S., McEnery M. W., Chin H., et al. . (2001). Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel. Mol. Cell. Neurosci. 18, 235–245. doi: 10.1006/mcne.2001.1013, PMID: PubMed DOI
La Porta C., Bura S. A., Aracil-Fernandez A., Manzanares J., Maldonado R. (2013). Role of CB1 and CB2 cannabinoid receptors in the development of joint pain induced by monosodium iodoacetate. Pain 154, 160–174. doi: 10.1016/j.pain.2012.10.009, PMID: PubMed DOI
Li Y., Adamek P., Zhang H., Tatsui C. E., Rhines L. D., Mrozkova P., et al. . (2015). The cancer chemotherapeutic paclitaxel increases human and rodent sensory neuron responses to TRPV1 by activation of TLR4. J. Neurosci. 35, 13487–13500. doi: 10.1523/JNEUROSCI.1956-15.2015, PMID: PubMed DOI PMC
Mahmud A., Santha P., Paule C. C., Nagy I. (2009). Cannabinoid 1 receptor activation inhibits transient receptor potential vanilloid type 1 receptor-mediated cationic influx into rat cultured primary sensory neurons. Neuroscience 162, 1202–1211. doi: 10.1016/j.neuroscience.2009.05.024, PMID: PubMed DOI
Mrozkova P., Spicarova D., Palecek J. (2021). Spinal PAR2 activation contributes to hypersensitivity induced by peripheral inflammation in rats. Int. J. Mol. Sci. 22:991. doi: 10.3390/ijms22030991, PMID: PubMed DOI PMC
Nagy I., Fedonidis C., Paule C. C., Wahba J., Andrew P., Austin J., et al. . (2009). NAPE-PLD is involved in Anandamide synthesis in capsaicin-sensitive primary sensory neurons. J. Physiol. Sci. 59:422.
Nagy B., Fedonidis C., Photiou A., Wahba J., Paule C. C., Ma D., et al. . (2009). Capsaicin-sensitive primary sensory neurons in the mouse express N-Acyl phosphatidylethanolamine phospholipase D. Neuroscience 161, 572–577. doi: 10.1016/j.neuroscience.2009.03.047, PMID: PubMed DOI PMC
Nerandzic V., Mrozkova P., Adamek P., Spicarova D., Nagy I., Palecek J. (2018). Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N-arachidonoylphosphatidylethanolamine. Br. J. Pharmacol. 175, 2322–2336. doi: 10.1111/bph.13849, PMID: PubMed DOI PMC
Nichols R. A., Suplick G. R., Brown J. M. (1994). Calcineurin-mediated protein dephosphorylation in brain nerve terminals regulates the release of glutamate. J. Biol. Chem. 269, 23817–23823. doi: 10.1016/S0021-9258(17)31588-0, PMID: PubMed DOI
Nyilas R., Gregg L. C., Mackie K., Watanabe M., Zimmer A., Hohmann A. G., et al. . (2009). Molecular architecture of endocannabinoid signaling at nociceptive synapses mediating analgesia. Eur. J. Neurosci. 29, 1964–1978. doi: 10.1111/j.1460-9568.2009.06751.x, PMID: PubMed DOI PMC
Park J., Luo Z. D. (2010). Calcium channel functions in pain processing. Channels (Austin) 4, 510–517. doi: 10.4161/chan.4.6.12869, PMID: PubMed DOI PMC
Pertwee R. G. (2006). The pharmacology of cannabinoid receptors and their ligands: an overview. Int. J. Obes. 30, S13–S18. doi: 10.1038/sj.ijo.0803272 PubMed DOI
Pertwee R. G. (2009). Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br. J. Pharmacol. 156, 397–411. doi: 10.1111/j.1476-5381.2008.00048.x, PMID: PubMed DOI PMC
Pospisilova E., Palecek J. (2006). Post-operative pain behavior in rats is reduced after single high-concentration capsaicin application. Pain 125, 233–243. doi: 10.1016/j.pain.2006.05.021, PMID: PubMed DOI
Rimmerman N., Hughes H. V., Bradshaw H. B., Pazos M. X., Mackie K., Prieto A. L., et al. . (2008). Compartmentalization of endocannabinoids into lipid rafts in a dorsal root ganglion cell line. Br. J. Pharmacol. 153, 380–389. doi: 10.1038/sj.bjp.0707561, PMID: PubMed DOI PMC
Santha P., Jenes A., Somogyi C., Nagy I. (2010). The endogenous cannabinoid anandamide inhibits transient receptor potential vanilloid type 1 receptor-mediated currents in rat cultured primary sensory neurons. Acta Physiol. Hung. 97, 149–158. doi: 10.1556/APhysiol.97.2010.2.1, PMID: PubMed DOI
Sihra T. S., Nairn A. C., Kloppenburg P., Lin Z., Pouzat C. (1995). A role for calcineurin (protein phosphatase-2B) in the regulation of glutamate release. Biochem. Biophys. Res. Commun. 212, 609–616. doi: 10.1006/bbrc.1995.2013, PMID: PubMed DOI
Snider N. T., Walker V. J., Hollenberg P. F. (2010). Oxidation of the endogenous cannabinoid arachidonoyl ethanolamide by the cytochrome P450 monooxygenases: physiological and pharmacological implications. Pharmacol. Rev. 62, 136–154. doi: 10.1124/pr.109.001081, PMID: PubMed DOI PMC
Sousa-Valente J., Andreou A. P., Urban L., Nagy I. (2014). Transient receptor potential ion channels in primary sensory neurons as targets for novel analgesics. Br. J. Pharmacol. 171, 2508–2527. doi: 10.1111/bph.12532, PMID: PubMed DOI PMC
Sousa-Valente J., Varga A., Torres-Perez J. V., Jenes A., Wahba J., Mackie K., et al. . (2017). Inflammation of peripheral tissues and injury to peripheral nerves induce differing effects in the expression of the calcium-sensitive N-arachydonoylethanolamine-synthesizing enzyme and related molecules in rat primary sensory neurons. J. Comp. Neurol. 525, 1778–1796. doi: 10.1002/cne.24154, PMID: PubMed DOI
Spicarova D., Adamek P., Kalynovska N., Mrozkova P., Palecek J. (2014a). TRPV1 receptor inhibition decreases CCL2-induced hyperalgesia. Neuropharmacology 81, 75–84. doi: 10.1016/j.neuropharm.2014.01.041, PMID: PubMed DOI
Spicarova D., Nerandzic V., Palecek J. (2011). Modulation of spinal cord synaptic activity by tumor necrosis factor alpha in a model of peripheral neuropathy. J. Neuroinflammation 8:177. doi: 10.1186/1742-2094-8-177, PMID: PubMed DOI PMC
Spicarova D., Nerandzic V., Palecek J. (2014b). Update on the role of spinal cord TRPV1 receptors in pain modulation. Physiol. Res. 63, S225–S236. doi: 10.33549/physiolres.932713, PMID: PubMed DOI
Spicarova D., Palecek J. (2008). The role of spinal cord vanilloid (TRPV1) receptors in pain modulation. Physiol. Res. 57, S69–S77. doi: 10.33549/physiolres.931601 PubMed DOI
Spicarova D., Palecek J. (2009). The role of the TRPV1 endogenous agonist N-Oleoyldopamine in modulation of nociceptive signaling at the spinal cord level. J. Neurophysiol. 102, 234–243. doi: 10.1152/jn.00024.2009, PMID: PubMed DOI
Storti B., Di Rienzo C., Cardarelli F., Bizzarri R., Beltram F. (2015). Unveiling TRPV1 spatio-temporal organization in live cell membranes. PLoS One 10:e0116900. doi: 10.1371/journal.pone.0116900, PMID: PubMed DOI PMC
Tominaga M., Caterina M. J., Malmberg A. B., Rosen T. A., Gilbert H., Skinner K., et al. . (1998). The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21, 531–543. doi: 10.1016/s0896-6273(00)80564-4, PMID: PubMed DOI
Uchytilova E., Spicarova D., Palecek J. (2021). Hypersensitivity induced by intrathecal bradykinin administration is enhanced by N-oleoyldopamine (OLDA) and prevented by TRPV1 antagonist. Int. J. Mol. Sci. 22:712. doi: 10.3390/ijms22073712, PMID: PubMed DOI PMC
van der Stelt M., Trevisani M., Vellani V., De Petrocellis L., Schiano Moriello A., Campi B., et al. . (2005). Anandamide acts as an intracellular messenger amplifying Ca2+ influx via TRPV1 channels. EMBO J. 24, 3026–3037. doi: 10.1038/sj.emboj.7600784, PMID: PubMed DOI PMC
Varga A., Jenes A., Marczylo T. H., Sousa-Valente J., Chen J., Austin J., et al. . (2014). Anandamide produced by Ca(2+)-insensitive enzymes induces excitation in primary sensory neurons. Pflugers Arch. 466, 1421–1435. doi: 10.1007/s00424-013-1360-7, PMID: PubMed DOI
Vellani V., Petrosino S., De Petrocellis L., Valenti M., Prandini M., Magherini P. C., et al. . (2008). Functional lipidomics. Calcium-independent activation of endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein kinases C and A and thrombin. Neuropharmacology 55, 1274–1279. doi: 10.1016/j.neuropharm.2008.01.010, PMID: PubMed DOI
Veress G., Meszar Z., Muszil D., Avelino A., Matesz K., Mackie K., et al. . (2013). Characterisation of cannabinoid 1 receptor expression in the perikarya, and peripheral and spinal processes of primary sensory neurons. Brain Struct. Funct. 218, 733–750. doi: 10.1007/s00429-012-0425-2, PMID: PubMed DOI PMC
Wang J., Okamoto Y., Morishita J., Tsuboi K., Miyatake A., Ueda N. (2006). Functional analysis of the purified anandamide-generating phospholipase D as a member of the metallo-beta-lactamase family. J. Biol. Chem. 281, 12325–12335. doi: 10.1074/jbc.M512359200, PMID: PubMed DOI
Wang J., Ueda N. (2009). Biology of endocannabinoid synthesis system. Prostaglandins Other Lipid Mediat. 89, 112–119. doi: 10.1016/j.prostaglandins.2008.12.002 PubMed DOI
Woodhams S. G., Wong A., Barrett D. A., Bennett A. J., Chapman V., Alexander S. P. (2012). Spinal administration of the monoacylglycerol lipase inhibitor JZL184 produces robust inhibitory effects on nociceptive processing and the development of central sensitization in the rat. Br. J. Pharmacol. 167, 1609–1619. doi: 10.1111/j.1476-5381.2012.02179.x, PMID: PubMed DOI PMC
Wu Z. Z., Chen S. R., Pan H. L. (2005). Transient receptor potential vanilloid type 1 activation down-regulates voltage-gated calcium channels through calcium-dependent calcineurin in sensory neurons. J. Biol. Chem. 280, 18142–18151. doi: 10.1074/jbc.M501229200, PMID: PubMed DOI
Wu Z. Z., Chen S. R., Pan H. L. (2006). Signaling mechanisms of down-regulation of voltage-activated Ca2+ channels by transient receptor potential vanilloid type 1 stimulation with olvanil in primary sensory neurons. Neuroscience 141, 407–419. doi: 10.1016/j.neuroscience.2006.03.023, PMID: PubMed DOI
Wu Y., Liu Y., Hou P., Yan Z., Kong W., Liu B., et al. . (2013). TRPV1 channels are functionally coupled with BK(mSlo1) channels in rat dorsal root ganglion (DRG) neurons. PLoS One 8:e78203. doi: 10.1371/journal.pone.0078203, PMID: PubMed DOI PMC
Yu L., Yang F., Luo H., Liu F. Y., Han J. S., Xing G. G., et al. . (2008). The role of TRPV1 in different subtypes of dorsal root ganglion neurons in rat chronic inflammatory nociception induced by complete Freund's adjuvant. Mol. Pain 4:61. doi: 10.1186/1744-8069-4-61, PMID: PubMed DOI PMC
Zygmunt P. M., Petersson J., Andersson D. A., Chuang H., Sorgard M., Di Marzo V., et al. . (1999). Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400, 452–457. doi: 10.1038/22761, PMID: PubMed DOI
Anandamide-Mediated Modulation of Nociceptive Transmission at the Spinal Cord Level