Back
 PP  Vol.6 No.3 , March 2015
Anandamide Depresses Glycinergic and GABAergic Inhibitory Transmissions in Adult Rat Substantia Gelatinosa Neurons
Abstract: Cannabinoid CB1 receptors have been found in the superficial dorsal horn of the spinal cord, particularly the substantia gelatinosa (SG), which is thought to play a pivotal role in modulating nociceptive transmission. Although cannabinoids are known to inhibit excitatory transmission in SG neurons, their effects on inhibitory transmission have not yet been examined fully. In order to know further about a role of cannabinoids in regulating nociceptive transmission, we examined the effects of cannabinoids on inhibitory transmissions in adult rat SG neurons using whole-cell voltage-clamp recordings. Anandamide (10 μM) superfused for 2 min reduced glycinergic and GABAergic electrically-evoked inhibitory postsynaptic current (IPSC) amplitudes; these actions persisted for more than 6 min after washout. Similar actions were produced by cannabinoid-receptor agonist WIN55,212-2 (5 μM) and 2-arachidonoyl glycerol (20 μM). The evoked IPSC amplitudes reduced by anandamide recovered to the control level following superfusion of CB1-receptor antagonist SR141716A (5 μM). A ratio of the second to first evoked IPSC amplitude in paired-pulse experiments was increased by anandamide (10 μM). The frequencies of glycinergic and GABAergic spontaneous IPSCs were reduced by anandamide (10 μM) without a change in their amplitudes. It is concluded that cannabinoids depress inhibitory transmissions in adult rat SG neurons by activating CB1 receptors in nerve terminals. This action could contribute to the modulation of nociceptive transmission by cannabinoids.
Cite this paper: Kawasaki, Y. , Fujita, T. , Yang, K. and Kumamoto, E. (2015) Anandamide Depresses Glycinergic and GABAergic Inhibitory Transmissions in Adult Rat Substantia Gelatinosa Neurons. Pharmacology & Pharmacy, 6, 103-117. doi: 10.4236/pp.2015.63013.
References

[1]   Pertwee, R.G. (2001) Cannabinoid Receptors and Pain. Progress in Neurobiology, 63, 569-611.
http://dx.doi.org/10.1016/S0301-0082(00)00031-9

[2]   Freund, T.F., Katona, I. and Piomelli, D. (2003) Role of Endogenous Cannabinoids in Synaptic Signaling. Physiological Reviews, 83, 1017-1066.
http://dx.doi.org/10.1152/physrev.00004.2003

[3]   Walker, J.M. and Hohmann, A.G. (2005) Cannabinoid Mechanisms of Pain Suppression. Handbook of Experimental Pharmacology, 168, 509-554.
http://dx.doi.org/10.1007/3-540-26573-2_17

[4]   Manzanares, J., Julian, M.D. and Carrascosa, A. (2006) Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes. Current Neuropharmacology, 4, 239-257.
http://dx.doi.org/10.2174/157015906778019527

[5]   Lichtman, A.H. and Martin, B.R. (1991) Cannabinoid-Induced Antinociception Is Mediated by a Spinal α2-Noradrenergic Mechanism. Brain Research, 559, 309-314.
http://dx.doi.org/10.1016/0006-8993(91)90017-P

[6]   Hohmann, A.G., Tsou, K. and Walker, J.M. (1998) Cannabinoid Modulation of Wide Dynamic Range Neurons in the Lumbar Dorsal Horn of the Rat by Spinally Administered WIN55,212-2. Neuroscience Letters, 257, 119-122.
http://dx.doi.org/10.1016/S0304-3940(98)00802-7

[7]   Mailleux, P. and Vanderhaeghen, J.-J. (1992) Distribution of Neuronal Cannabinoid Receptor in the Adult Rat Brain: A Comparative Receptor Binding Radioautography and in Situ Hybridization Histochemistry. Neuroscience, 48, 655-668.
http://dx.doi.org/10.1016/0306-4522(92)90409-U

[8]   Hohmann, A.G., Briley, E.M. and Herkenham, M. (1999) Pre- and Postsynaptic Distribution of Cannabinoid and Mu Opioid Receptors in Rat Spinal Cord. Brain Research, 822, 17-25.
http://dx.doi.org/10.1016/S0006-8993(98)01321-3

[9]   Tsou, K., Brown, S., Sañudo-Peña, M.C., Mackie, K. and Walker, J.M. (1998) Immunohistochemical Distribution of Cannabinoid CB1 Receptors in the Rat Central Nervous System. Neuroscience, 83, 393-411.
http://dx.doi.org/10.1016/S0306-4522(97)00436-3

[10]   Farquhar-Smith, W.P., Egertová, M., Bradbury, E.J., McMahon, S.B., Rice, A.S.C. and Elphick, M.R. (2000) Cannabinoid CB1 Receptor Expression in Rat Spinal Cord. Molecular and Cellular Neuroscience, 15, 510-521.
http://dx.doi.org/10.1006/mcne.2000.0844

[11]   Salio, C., Fischer, J., Franzoni, M.F. and Conrath, M. (2002) Pre- and Postsynaptic Localizations of the CB1 Cannabinoid Receptor in the Dorsal Horn of the Rat Spinal Cord. Neuroscience, 110, 755-764.
http://dx.doi.org/10.1016/S0306-4522(01)00584-X

[12]   Hegyi, Z., Kis, G., Holló, K., Ledent, C. and Antal, M. (2009) Neuronal and Glial Localization of the Cannabinoid-1 Receptor in the Superficial Spinal Dorsal Horn of the Rodent Spinal Cord. European Journal of Neuroscience, 30, 251-262.
http://dx.doi.org/10.1111/j.1460-9568.2009.06816.x

[13]   Chapman, V. (1999) The Cannabinoid CB1 Receptor Antagonist, SR141716A, Selectively Facilitates Nociceptive Responses of Dorsal Horn Neurones in the Rat. British Journal of Pharmacology, 127, 1765-1767.
http://dx.doi.org/10.1038/sj.bjp.0702758

[14]   Willis Jr., W.D. and Coggeshall, R.E. (1991) Sensory Mechanisms of the Spinal Cord. 2nd Edition, Plenum Press, New York.
http://dx.doi.org/10.1007/978-1-4899-0597-0

[15]   Fürst, S. (1999) Transmitters Involved in Antinociception in the Spinal Cord. Brain Research Bulletin, 48, 129-141.
http://dx.doi.org/10.1016/S0361-9230(98)00159-2

[16]   Todd, A.J. (2010) Neuronal Circuitry for Pain Processing in the Dorsal Horn. Nature Reviews Neuroscience, 11, 823-836.
http://dx.doi.org/10.1038/nrn2947

[17]   Kohno, T., Kumamoto, E., Higashi, H., Shimoji, K. and Yoshimura, M. (1999) Actions of Opioids on Excitatory and Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord. Journal of Physiology (London), 518, 803-813.
http://dx.doi.org/10.1111/j.1469-7793.1999.0803p.x

[18]   Ito, A., Kumamoto, E., Takeda, M., Takeda, M., Shibata, K., Sagai, H. and Yoshimura, M. (2000) Mechanisms for Ovariectomy-Induced Hyperalgesia and Its Relief by Calcitonin: Participation of 5-HT1A-Like Receptor on C-Afferent Terminals in Substantia Gelatinosa of the Rat Spinal Cord. Journal of Neuroscience, 20, 6302-6308.

[19]   Luo, C., Kumamoto, E., Furue, H., Chen, J. and Yoshimura, M. (2002) Nociceptin Inhibits Excitatory but Not Inhibitory Transmission to Substantia Gelatinosa Neurones of Adult Rat Spinal Cord. Neuroscience, 109, 349-358.
http://dx.doi.org/10.1016/S0306-4522(01)00459-6

[20]   Kawasaki, Y., Kumamoto, E., Furue, H. and Yoshimura, M. (2003) α2 Adrenoceptor-Mediated Presynaptic Inhibition of Primary Afferent Glutamatergic Transmission in Rat Substantia Gelatinosa Neurons. Anesthesiology, 98, 682-689. http://dx.doi.org/10.1097/00000542-200303000-00016

[21]   Lao, L.J., Kawasaki, Y., Yang, K., Fujita, T. and Kumamoto, E. (2004) Modulation by Adenosine of Aδ and C Primary-Afferent Glutamatergic Transmission in Adult Rat Substantia Gelatinosa Neurons. Neuroscience, 125, 221-231.
http://dx.doi.org/10.1016/j.neuroscience.2004.01.029

[22]   Yue, H.Y., Fujita, T. and Kumamoto, E. (2011) Biphasic Modulation by Galanin of Excitatory Synaptic Transmission in Substantia Gelatinosa Neurons of Adult Rat Spinal Cord Slices. Journal of Neurophysiology, 105, 2337-2349.
http://dx.doi.org/10.1152/jn.00991.2010

[23]   Morisset, V. and Urban, L. (2001) Cannabinoid-Induced Presynaptic Inhibition of Glutamatergic EPSCs in Substantia Gelatinosa Neurons of the Rat Spinal Cord. Journal of Neurophysiology, 86, 40-48.

[24]   Luo, C., Kumamoto, E., Furue, H., Chen, J. and Yoshimura, M. (2002) Anandamide Inhibits Excitatory Transmission to Rat Substantia Gelatinosa Neurones in a Manner Different from that of Capsaicin. Neuroscience Letters, 321, 17-20.
http://dx.doi.org/10.1016/S0304-3940(01)02471-5

[25]   Liang, Y.C., Huang, C.C., Hsu, K.S. and Takahashi, T. (2004) Cannabinoid-Induced Presynaptic Inhibition at the Primary Afferent Trigeminal Synapse of Juvenile Rat Brainstem Slices. Journal of Physiology (London), 555, 85-96.
http://dx.doi.org/10.1113/jphysiol.2003.056986

[26]   Todd, A.J., Watt, C., Spike, R.C. and Sieghart, W. (1996) Colocalization of GABA, Glycine, and Their Receptors at Synapses in the Rat Spinal Cord. Journal of Neuroscience, 16, 974-982.

[27]   Sandkühler, J. (2009) Models and Mechanisms of Hyperalgesia and Allodynia. Physiological Reviews, 89, 707-758.
http://dx.doi.org/10.1152/physrev.00025.2008

[28]   Zeilhofer, H.U., Wildner, H. and Yévenes, G.E. (2012) Fast Synaptic Inhibition in Spinal Sensory Processing and Pain Control. Physiological Reviews, 92, 193-235.
http://dx.doi.org/10.1152/physrev.00043.2010

[29]   Moore, K.A., Kohno, T., Karchewski, L.A., Scholz, J., Baba, H. and Woolf, C.J. (2002) Partial Peripheral Nerve Injury Promotes a Selective Loss of GABAergic Inhibition in the Superficial Dorsal Horn of the Spinal Cord. Journal of Neuroscience, 22, 6724-6731.

[30]   Coull, J.A.M., Boudreau, D., Bachand, K., Prescott, S.A., Nault, F., Sik, A., de Koninck, P. and de Koninck, Y. (2003) Trans-Synaptic Shift in Anion Gradient in Spinal Lamina I Neurons as a Mechanism of Neuropathic Pain. Nature, 424, 938-942.
http://dx.doi.org/10.1038/nature01868

[31]   Baba, H., Shimoji, K. and Yoshimura, M. (2000) Norepinephrine Facilitates Inhibitory Transmission in Substantia Gelatinosa of Adult Rat Spinal Cord (Part 1): Effects on Axon Terminals of GABAergic and Glycinergic Neurons. Anesthesiology, 92, 473-484.
http://dx.doi.org/10.1097/00000542-200002000-00030

[32]   Baba, H., Kohno, T., Okamoto, M., Goldstein, P.A., Shimoji, K. and Yoshimura, M. (1998) Muscarinic Facilitation of GABA Release in Substantia Gelatinosa of the Rat Spinal Dorsal Horn. Journal of Physiology (London), 508, 83-93.
http://dx.doi.org/10.1111/j.1469-7793.1998.083br.x

[33]   Takeda, D., Nakatsuka, T., Papke, R. and Gu, J.G. (2003) Modulation of Inhibitory Synaptic Activity by a Non-α4β2, Non-α7 Subtype of Nicotinic Receptors in the Substantia Gelatinosa of Adult Rat Spinal Cord. Pain, 101, 13-23.
http://dx.doi.org/10.1016/S0304-3959(02)00074-X

[34]   Liu, T., Fujita, T. and Kumamoto, E. (2011) Acetylcholine and Norepinephrine Mediate GABAergic but Not Glycinergic Transmission Enhancement by Melittin in Adult Rat Substantia Gelatinosa Neurons. Journal of Neurophysiology, 106, 233-246.
http://dx.doi.org/10.1152/jn.00838.2010

[35]   Fukushima, T., Ohtsubo, T., Tsuda, M., Yanagawa, Y. and Hori, Y. (2009) Facilitatory Actions of Serotonin Type 3 Receptors on GABAergic Inhibitory Synaptic Transmission in the Spinal Superficial Dorsal Horn. Journal of Neurophysiology, 102, 1459-1471.
http://dx.doi.org/10.1152/jn.91160.2008

[36]   Breton, J.D., Veinante, P., Uhl-Bronner, S., Vergnano, A.M., Freund-Mercier, M.J., Schlichter, R. and Poisbeau, P. (2008) Oxytocin-Induced Antinociception in the Spinal Cord Is Mediated by a Subpopulation of Glutamatergic Neurons in Lamina I-II Which Amplify GABAergic Inhibition. Molecular Pain, 4, 19.
http://dx.doi.org/10.1186/1744-8069-4-19

[37]   Jiang, C.Y., Fujita, T. and Kumamoto, E. (2014) Synaptic Modulation and Inward Current Produced by Oxytocin in Substantia Gelatinosa Neurons of Adult Rat Spinal Cord Slices. Journal of Neurophysiology, 111, 991-1007.
http://dx.doi.org/10.1152/jn.00609.2013

[38]   Yang, K., Fujita, T. and Kumamoto, E. (2004) Adenosine Inhibits GABAergic and Glycinergic Transmission in Adult Rat Substantia Gelatinosa Neurons. Journal of Neurophysiology, 92, 2867-2877.
http://dx.doi.org/10.1152/jn.00291.2004

[39]   Szabo, B., Dörner, L., Pfreundtner, C., Nörenberg, W. and Starke, K. (1998) Inhibition of GABAergic Inhibitory Postsynaptic Currents by Cannabinoids in Rat Corpus Striatum. Neuroscience, 85, 395-403.
http://dx.doi.org/10.1016/S0306-4522(97)00597-6

[40]   Hoffman, A.F. and Lupica, C.R. (2000) Mechanisms of Cannabinoid Inhibition of GABAA Synaptic Transmission in the Hippocampus. Journal of Neuroscience, 20, 2470-2479.

[41]   Wilson, R.I. and Nicoll, R.A. (2001) Endogenous Cannabinoids Mediate Retrograde Signalling at Hippocampal Synapses. Nature, 410, 588-592.
http://dx.doi.org/10.1038/35069076

[42]   Jennings, E.A., Vaughan, C.W. and Christie, M.J. (2001) Cannabinoid Actions on Rat Superficial Medullary Dorsal Horn Neurons in Vitro. Journal of Physiology (London), 534, 805-812.
http://dx.doi.org/10.1111/j.1469-7793.2001.00805.x

[43]   Wallmichrath, I. and Szabo, B. (2002) Analysis of the Effect of Cannabinoids on GABAergic Neurotransmission in the Substantia Nigra Pars Reticulata. Naunyn-Schmiedeberg’s Archives of Pharmacology, 365, 326-334.
http://dx.doi.org/10.1007/s00210-001-0520-z

[44]   Pernía-Andrade, A.J., Kato, A., Witschi, R., Nyilas, R., Katona, I., Freund, T.F., Watanabe, M., Filitz, J., Koppert, W., Schüttler, J., Ji, G., Neugebauer, V., Marsicano, G., Lutz, B., Vanegas, H. and Zeilhofer, H.U. (2009) Spinal Endocannabinoids and CB1 Receptors Mediate C-Fiber-Induced Heterosynaptic Pain Sensitization. Science, 325, 760-764.
http://dx.doi.org/10.1126/science.1171870

[45]   Yang, H.Y.T., Karoum, F., Felder, C., Badger, H., Wang, T.C.L. and Markey, S.P. (1999) GC/MS Analysis of Anandamide and Quantification of N-Arachidonoylphosphatidylethanolamides in Various Brain Regions, Spinal Cord, Testis, and Spleen of the Rat. Journal of Neurochemistry, 72, 1959-1968.
http://dx.doi.org/10.1046/j.1471-4159.1999.0721959.x

[46]   Kawasaki, Y., Yang, K., Lao, L.J., Matsumoto, N., Fujita, T., Kumamoto, E. and Hasuo, H. (2002) Action of Anandamide on Inhibitory Transmission to Substantia Gelatinosa Neurons in the Rat Spinal Cord. Society for Neuroscience Abstract, 453.4.

[47]   Fujita, T., Liu, T., Nakatsuka, T. and Kumamoto, E. (2009) Proteinase-Activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons. Journal of Neurophysiology, 102, 312-319.
http://dx.doi.org/10.1152/jn.91117.2008

[48]   Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A. and Waku, K. (1995) 2-Arachidonoylglycerol: A Possible Endogenous Cannabinoid Receptor Ligand in Brain. Biochemical and Biophysical Research Communications, 215, 89-97.
http://dx.doi.org/10.1006/bbrc.1995.2437

[49]   Di Marzo, V., Breivogel, C.S., Tao, Q., Bridgen, D.T., Razdan, R.K., Zimmer, A.M., Zimmer, A. and Martin, B.R. (2000) Levels, Metabolism, and Pharmacological Activity of Anandamide in CB1 Cannabinoid Receptor Knockout Mice: Evidence for Non-CB1, Non-CB2 Receptor-Mediated Actions of Anandamide in Mouse Brain. Journal of Neurochemistry, 75, 2434-2444.
http://dx.doi.org/10.1046/j.1471-4159.2000.0752434.x

[50]   Zygmunt, P.M., Petersson, J., Andersson, D.A., Chuang, H.H., Sørgård, M., Di Marzo, V., Julius, D. and Högestätt, E.D. (1999) Vanilloid Receptors on Sensory Nerves Mediate the Vasodilator Action of Anandamide. Nature, 400, 452-457.
http://dx.doi.org/10.1038/22761

[51]   De Petrocellis, L., Bisogno, T., Maccarrone, M., Davis, J.B., Finazzi-Agrò, A. and Di Marzo, V. (2001) The Activity of Anandamide at Vanilloid VR1 Receptors Requires Facilitated Transport across the Cell Membrane and Is Limited by Intracellular Metabolism. Journal of Biological Chemistry, 276, 12856-12863.
http://dx.doi.org/10.1074/jbc.M008555200

[52]   Morisset, V., Ahluwalia, J., Nagy, I. and Urban, L. (2001) Possible Mechanisms of Cannabinoid-Induced Antinociception in the Spinal Cord. European Journal of Pharmacology, 429, 93-100.
http://dx.doi.org/10.1016/S0014-2999(01)01309-7

[53]   Jennings, E.A., Vaughan, C.W., Roberts, L.A. and Christie, M.J. (2003) The Actions of Anandamide on Rat Superficial Medullary Dorsal Horn Neurons in Vitro. Journal of Physiology (London), 548, 121-129.
http://dx.doi.org/10.1113/jphysiol.2002.035063

[54]   Yang, K., Kumamoto, E., Furue, H. and Yoshimura, M. (1998) Capsaicin Facilitates Excitatory but Not Inhibitory Synaptic Transmission in Substantia Gelatinosa of the Rat Spinal Cord. Neuroscience Letters, 255, 135-138.
http://dx.doi.org/10.1016/S0304-3940(98)00730-7

[55]   Yang, K., Kumamoto, E., Furue, H., Li, Y.Q. and Yoshimura, M. (1999) Action of Capsaicin on Dorsal Root-Evoked Synaptic Transmission to Substantia Gelatinosa Neurons in Adult Rat Spinal Cord Slices. Brain Research, 830, 268-273.
http://dx.doi.org/10.1016/S0006-8993(99)01408-0

[56]   Kumamoto, E., Fujita, T. and Jiang, C.Y. (2014) TRP Channels Involved in Spontaneous L-Glutamate Release Enhancement in the Adult Rat Spinal Substantia Gelatinosa. Cells, 3, 331-362.
http://dx.doi.org/10.3390/cells3020331

[57]   Savinainen, J.R., Järvinen, T., Laine, K. and Laitinen, J.T. (2001) Despite Substantial Degradation, 2-Arachidonoylgly-cerol Is a Potent Full Efficacy Agonist Mediating CB1 Receptor-Dependent G-Protein Activation in Rat Cerebellar Membranes. British Journal of Pharmacology, 134, 664-672.
http://dx.doi.org/10.1038/sj.bjp.0704297

[58]   Ueda, N., Goparaju, S.K., Katayama, K., Kurahashi, Y., Suzuki, H. and Yamamoto, S. (1998) A Hydrolase Enzyme Inactivating Endogenous Ligands for Cannabinoid Receptors. Journal of Medical Investigation, 45, 27-36.

[59]   Todd, A.J. and Spike, R.C. (1993) The Localization of Classical Transmitters and Neuropeptides within Neurons in Laminae I-III of the Mammalian Spinal Dorsal Horn. Progress in Neurobiology, 41, 609-645.
http://dx.doi.org/10.1016/0301-0082(93)90045-T

[60]   Akaike, N. and Moorhouse, A.J. (2003) Techniques: Applications of the Nerve-Bouton Preparation in Neuropharmacology. Trends in Pharmacological Sciences, 24, 44-47.
http://dx.doi.org/10.1016/S0165-6147(02)00010-X

[61]   Mackie, K., Lai, Y., Westenbroek, R. and Mitchell, R. (1995) Cannabinoids Activate an Inwardly Rectifying Potassium Conductance and Inhibit Q-Type Calcium Currents in AtT20 Cells Transfected with Rat Brain Cannabinoid Receptor. Journal of Neuroscience, 15, 6552-6561.

[62]   Twitchell, W., Brown, S. and Mackie, K. (1997) Cannabinoids Inhibit N- and P/Q-Type Calcium Channels in Cultured Rat Hippocampal Neurons. Journal of Neurophysiology, 78, 43-50.

[63]   Liu, T., Fujita, T., Nakatsuka, T. and Kumamoto, E. (2008) Phospholipase A2 Activation Enhances Inhibitory Synaptic Transmission in Rat Substantia Gelatinosa Neurons. Journal of Neurophysiology, 99, 1274-1284.
http://dx.doi.org/10.1152/jn.01292.2007

[64]   Mason Jr., D.J., Lowe, J. and Welch, S.P. (1999) Cannabinoid Modulation of Dynorphin A: Correlation to Cannabinoid-Induced Antinociception. European Journal of Pharmacology, 378, 237-248.
http://dx.doi.org/10.1016/S0014-2999(99)00479-3

[65]   Kano, M., Ohno-Shosaku, T., Hashimotodani, Y., Uchigashima, M. and Watanabe, M. (2009) Endocannabinoid-Mediated Control of Synaptic Transmission. Physiological Reviews, 89, 309-380.
http://dx.doi.org/10.1152/physrev.00019.2008

[66]   Ohno-Shosaku, T. and Kano, M. (2014) Endocannabinoid-Mediated Retrograde Modulation of Synaptic Transmission. Current Opinion in Neurobiology, 29, 1-8.
http://dx.doi.org/10.1016/j.conb.2014.03.017

[67]   Hashimotodani, Y., Ohno-Shosaku, T., Yamazaki, M., Sakimura, K. and Kano, M. (2011) Neuronal Protease-Activated Receptor 1 Drives Synaptic Retrograde Signaling Mediated by the Endocannabinoid 2-Arachidonoylglycerol. Journal of Neuroscience, 31, 3104-3109.
http://dx.doi.org/10.1523/JNEUROSCI.6000-10.2011

 
 
Top