Abstract
Opiates are the most powerful of all known analgesics. The prototype opiate morphine has been used as a painkiller for several thousand years. Chronic usage of opiates not only causes drug tolerance, dependence, and addiction, but also suppresses immune functions and affects cell proliferation and cell survival. The diverse functions of opiates underscore the complexity of opioid receptor signaling. Several downstream signaling effector systems, including adenylyl cyclase, mitogen-activated protein kinase, Ca2+ channels, K+ channels, and phosphatidylinositol 3-kinase/Akt, have been identified to be critical in opioid functions. Nuclear factor-κB (NF-κB), one of the most diverse and critical transcription factors, is one of the downstream molecules that may either directly or indirectly transmit the receptor-mediated upstream signals to the nucleus, resulting in the regulation of the NF-κB-dependent genes, which are critical for the opioid-induced biological responses of neuronal and immune cells. In this minireview, we focus on current understanding of the involvement of NF-κB signaling in opioid functions and receptor gene expression in cells.
Similar content being viewed by others
References
Ai W, Gong J, Yu L (1999) MAP kinase activation by mu opioid receptor involves phosphatidylinositol 3-kinase but not the cAMP/PKA pathway. FEBS Lett 456:196–200
Augustin LB, Felsheim RF, Min BH, Fuchs SM, Fuchs JA, Loh HH (1995) Genomic structure of the mouse delta opioid receptor gene. Biochem Biophys Res Commun 207:111–119
Azuma Y, Ohura K (2002) Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NF-kappaB DNA binding in THP-1 differentiated to macrophage-like cells. Scand J Immunol 56:260–269
Baeuerle PA, Baltimore D (1996) NF-kappa B: ten years after. Cell 87:13–20
Barger SW, Horster D, Furukawa K, Goodman Y, Krieglstein J, Mattson MP (1995) Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and Ca2+ accumulation. Proc Natl Acad Sci USA 92: 9328–9332
Bohn LM, Gainetdinov RR, Lin FT, Lefkowitz RJ, Caron MG (2000) Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408:720–723
Borlongan CV, Wang Y, Su TP (2004) Delta opioid peptide (d-Ala 2, d-Leu 5) enkephalin: linking hibernation and neuroprotection. Front Biosci 9:3392–3398
Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297–305
Capasso A (2001) Involvement of nuclear factor-κB in the expression of opiate withdrawal. Prog Neuro-psychopharmacol Biol Psychiatry 25:1259–1268
Carr DJ, Carpenter GW, Garza HH Jr, France CP, Prakash OM (1995) Chronic and infrequent opioid exposure suppresses IL-2R expression on rhesus monkey peripheral blood mononuclear cells following stimulation with pokeweed mitogen. Int J Neurosci 81:137–148
Carter BD, Kaltschmidt C, Kaltschmidt B, Offenhauser N, Bohm-Matthaei R, Baeuerle PA, Barde YA (1996) Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75. Science 272:542–545
Chen LF, Greene WC (2004) Shaping the nuclear action of NF-kappaB. Nat Rev Mol Cell Biol 5:392–401
Chen Y, Mestek A, Liu J, Yu L (1993) Molecular cloning of a rat kappa opioid receptor reveals sequence similarities to the mu and delta opioid receptors. Biochem J 295(Pt 3):625–628
Chen YL, Law PY, Loh HH (2006) Sustained activation of phosphatidylinositol 3-kinase/akt/nuclear factor {kappa}B signaling mediates G protein-coupled {delta}-opioid receptor gene expression. J Biol Chem 281:3067–3074
Chuang LF, Killam KF Jr, Chuang RY (1997) Induction and activation of mitogen-activated protein kinases of human lymphocytes as one of the signaling pathways of the immunomodulatory effects of morphine sulfate. J Biol Chem 272:26815–26817
Colasanti M, Persichini T (2000) Nitric oxide: an inhibitor of NF-kappaB/Rel system in glial cells. Brain Res Bull 52:155–161
Collier HO, Francis DL (1975) Morphine abstinence is associated with increased brain cyclic AMP. Nature 255:159–162
Conant K, Ma M, Nath A, Major EO (1996) Extracellular human immunodeficiency virus type 1 Tat protein is associated with an increase in both NF-kappa B binding and protein kinase C activity in primary human astrocytes. J Virol 70:1384–1389
Czlonkowski A, Stein C, Herz A (1993) Peripheral mechanisms of opioid antinociception in inflammation: involvement of cytokines. Eur J Pharmacol 242:229–235
DelaTorre A, Schroeder RA, Kuo PC (1997) Alteration of NF-kappa B p50 DNA binding kinetics by S-nitrosylation. Biochem Biophys Res Commun 238:703–706
Dixit V, Mak TW (2002) NF-kappaB signaling. Many roads lead to madrid. Cell 111:615–619
Evans CJ, Keith DE Jr, Morrison H, Magendzo K, Edwards RH (1992) Cloning of a delta opioid receptor by functional expression. Science 258:1952–1955
Fischer EG (1988) Opioid peptides modulate immune functions. A review. Immunopharmacol Immunotoxicol 10:265–326
Fukuda K, Kato S, Mori K, Nishi M, Takeshima H (1993) Primary structures and expression from cDNAs of rat opioid receptor delta- and mu-subtypes. FEBS Lett 327:311–314
Fukuda K, Kato S, Morikawa H, Shoda T, Mori K (1996) Functional coupling of the delta-, mu-, and kappa-opioid receptors to mitogen-activated protein kinase and arachidonate release in Chinese hamster ovary cells. J Neurochem 67:1309–1316
Gao H, Sun Y, Wu Y, Luan B, Wang Y, Qu B, Pei G (2004) Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways. Mol Cell 14:303–317
Gaveriaux C, Peluso J, Simonin F, Laforet J, Kieffer B (1995) Identification of kappa- and delta-opioid receptor transcripts in immune cells. FEBS Lett 369:272–276
Gaveriaux-Ruff C, Matthes HW, Peluso J, Kieffer BL (1998) Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor gene. Proc Natl Acad Sci USA 95:6326–6330
Georges F, Normand E, Bloch B, Le Moine C (1998) Opioid receptor gene expression in the rat brain during ontogeny, with special reference to the mesostriatal system: an in situ hybridization study. Brain Res Dev Brain Res 109:187–199
Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109(Suppl):S81–S96
Guerrini L, Blasi F, Denis-Donini S (1995) Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro. Proc Natl Acad Sci USA 92:9077–9081
Henry DJ, Grandy DK, Lester HA, Davidson N, Chavkin C (1995) Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes. Mol Pharmacol 47:551–557
Hirano F, Tanaka H, Hirano Y, Hiramoto M, Handa H, Makino I, Scheidereit C (1998) Functional interference of Sp1 and NF-kappaB through the same DNA binding site. Mol Cell Biol 18:1266–1274
Hou YN, Vlaskovska M, Cebers G, Kasakov L, Liljequist S, Terenius L (1996) A mu-receptor opioid agonist induces AP-1 and NF-kappa B transcription factor activity in primary cultures of rat cortical neurons. Neurosci Lett 212:159–162
Kieffer BL, Gaveriaux-Ruff C (2002) Exploring the opioid system by gene knockout. Prog Neurobiol 66:285–306
Kieffer BL, Befort K, Gaveriaux-Ruff C, Hirth CG (1992) The delta-opioid receptor: isolation of a cDNA by expression cloning and pharmacological characterization. Proc Natl Acad Sci USA 89:12048–12052
Kraus J, Borner C, Giannini E, Hollt V (2003) The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene. Mol Pharmacol 64:876–884
Law PY, Wong YH, Loh HH (2000) Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol 40:389–430
Law PY, Loh HH, Wei LN (2004) Insights into the receptor transcription and signaling: implications in opioid tolerance and dependence. Neuropharmacology 47(Suppl 1):300–311
Lawrence DM, el-Hamouly W, Archer S, Leary JF, Bidlack JM (1995) Identification of kappa opioid receptors in the immune system by indirect immunofluorescence. Proc Natl Acad Sci USA 92:1062–1066
Lezoualc'h F, Sagara Y, Holsboer F, Behl C (1998) High constitutive NF-kappaB activity mediates resistance to oxidative stress in neuronal cells. J Neurosci 18:3224–3232
Li LY, Chang KJ (1996) The stimulatory effect of opioids on mitogen-activated protein kinase in Chinese hamster ovary cells transfected to express mu-opioid receptors. Mol Pharmacol 50:599–602
Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2:725–734
Li S, Zhu J, Chen C, Chen YW, Deriel JK, Ashby B, Liu-Chen LY (1993) Molecular cloning and expression of a rat kappa opioid receptor. Biochem J 295(Pt 3):629–633
Li MD, McAllen K, Sharp BM (1999) Regulation of delta opioid receptor expression by anti-CD3-epsilon, PMA, and ionomycin in murine splenocytes and T cells. J Leukoc Biol 65:707–714
Li Y, Zhang T, Douglas SD, Lai JP, Xiao WD, Pleasure DE, Ho WZ (2003) Morphine enhances hepatitis C virus (HCV) replicon expression. Am J Pathol 163:1167–1175
Lieb K, Fiebich BL, Berger M, Bauer J, Schulze-Osthoff K (1997) The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells. J Immunol 159:4952–4958
Magazine HI, Liu Y, Bilfinger TV, Fricchione GL, Stefano GB (1996) Morphine-induced conformational changes in human monocytes, granulocytes, and endothelial cells and in invertebrate immunocytes and microglia are mediated by nitric oxide. J Immunol 156:4845–4850
Maggirwar SB, Sarmiere PD, Dewhurst S, Freeman RS (1998) Nerve growth factor-dependent activation of NF-kappaB contributes to survival of sympathetic neurons. J Neurosci 18:10356–10365
Marshall HE, Hess DT, Stamler JS (2004) S-Nitrosylation: physiological regulation of NF-kappaB. Proc Natl Acad Sci USA 101:8841–8842
Matthews JR, Botting CH, Panico M, Morris HR, Hay RT (1996) Inhibition of NF-kappaB DNA binding by nitric oxide. Nucleic Acids Res 24:2236–2242
Mattson MP (2003) Insulating axons via NF-kappaB. Nat Neurosci 6:105–106
McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ (2001) Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 62:111–123
Meffert MK, Baltimore D (2005) Physiological functions for brain NF-kappaB. Trends Neurosci 28:37–43
Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D (2003) NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci 6:1072–1078
Meng F, Xie GX, Thompson RC, Mansour A, Goldstein A, Watson SJ, Akil H (1993) Cloning and pharmacological characterization of a rat kappa opioid receptor. Proc Natl Acad Sci USA 90:9954–9958
Middleton G, Wyatt S, Ninkina N, Davies AM (2001) Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival. Development 128:447–457
Miyamae T, Fukushima N, Misu Y, Ueda H (1993) Delta opioid receptor mediates phospholipase C activation via Gi in Xenopus oocytes. FEBS Lett 333:311–314
Murphy TJ (2003) Simple nuclear factor kappaB-mediated mu-opioid receptor induction in immune cells. Mol Pharmacol 64:796–797
Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB (1996) Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci USA 93:9090–9095
Nestler EJ (1992) Molecular mechanisms of drug addiction. J Neurosci 12:2439–2450
Nestler EJ (1997) Molecular mechanisms of opiate and cocaine addiction. Curr Opin Neurobiol 7:713–719
Nestler EJ (2004) Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol Sci 25:210–218
Nickols JC, Valentine W, Kanwal S, Carter BD (2003) Activation of the transcription factor NF-kappaB in Schwann cells is required for peripheral myelin formation. Nat Neurosci 6:161–167
O'Neill LA, Kaltschmidt C (1997) NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 20:252–258
Ozawa T, Nakagawa T, Minami M, Satoh M (1999) Supersensitization of the adenylyl cyclase system in Chinese hamster ovary cells co-expressing cloned opioid receptors and Gz, a PTX-insensitive G protein. Neurosci Lett 267:117–120
Park SW, Wei LN (2003) Regulation of c-myc gene by nitric oxide via inactivating NF-kappa B complex in P19 mouse embryonal carcinoma cells. J Biol Chem 278:29776–29782
Park SW, Li J, Loh HH, Wei LN (2002) A novel signaling pathway of nitric oxide on transcriptional regulation of mouse kappa opioid receptor gene. J Neurosci 22:7941–7947
Park SW, Huq MD, Hu X, Wei LN (2005) Tyrosine nitration on p65: a novel mechanism to rapidly inactivate nuclear factor-kappaB. Mol Cell Proteomics 4:300–309
Parry GC, Mackman N (1997) Role of cyclic AMP response element-binding protein in cyclic AMP inhibition of NF-kappaB-mediated transcription. J Immunol 159:5450–5456
Philippe D, Chakass D, Thuru X, Zerbib P, Tsicopoulos A, Geboes K, Bulois P, Breisse M, Vorng H, Gay J, Colombel JF, Desreumaux P, Chamaillard M (2006) Mu opioid receptor expression is increased in inflammatory bowel diseases: implications for homeostatic intestinal inflammation. Gut 55:815–823
Piros ET, Prather PL, Loh HH, Law PY, Evans CJ, Hales TG (1995) Ca2+ channel and adenylyl cyclase modulation by cloned mu-opioid receptors in GH3 cells. Mol Pharmacol 47:1041–1049
Pol O, Alameda F, Puig MM (2001) Inflammation enhances mu-opioid receptor transcription and expression in mice intestine. Mol Pharmacol 60:894–899
Polakiewicz RD, Schieferl SM, Dorner LF, Kansra V, Comb MJ (1998a) A mitogen-activated protein kinase pathway is required for mu-opioid receptor desensitization. J Biol Chem 273:12402–12406
Polakiewicz RD, Schieferl SM, Gingras AC, Sonenberg N, Comb MJ (1998b) mu-Opioid receptor activates signaling pathways implicated in cell survival and translational control. J Biol Chem 273:23534–23541
Pomerantz JL, Baltimore D (2002) Two pathways to NF-kappaB. Mol Cell 10:693–695
Prather PL, Loh HH, Law PY (1994) Interaction of delta-opioid receptors with multiple G proteins: a non-relationship between agonist potency to inhibit adenylyl cyclase and to activate G proteins. Mol Pharmacol 45:997–1003
Rogers TJ, Peterson PK (2003) Opioid G protein-coupled receptors: signals at the crossroads of inflammation. Trends Immunol 24:116–121
Rojo AI, Salinas M, Martin D, Perona R, Cuadrado A (2004) Regulation of Cu/Zn-superoxide dismutase expression via the phosphatidylinositol 3 kinase/Akt pathway and nuclear factor-kappaB. J Neurosci 24:7324–7334
Roy S, Barke RA, Loh HH (1998a) Mu-opioid receptor-knockout mice: role of mu-opioid receptor in morphine mediated immune functions. Brain Res Mol Brain Res 61:190–194
Roy S, Cain KJ, Chapin RB, Charboneau RG, Barke RA (1998b) Morphine modulates NF kappa B activation in macrophages. Biochem Biophys Res Commun 245:392–396
Rozenfeld-Granot G, Toren A, Amariglio N, Nagler A, Rosenthal E, Biniaminov M, Brok-Simoni F, Rechavi G (2002) MAP kinase activation by mu opioid receptor in cord blood CD34(+)CD38(−) cells. Exp Hematol 30:473–480
Salzet M, Vieau D, Day R (2000) Crosstalk between nervous and immune systems through the animal kingdom: focus on opioids. Trends Neurosci 23:550–555
Schmitz R (1985) Friedrich Wilhelm Serturner and the discovery of morphine. Pharm Hist 27:61–74
Shahabi NA, McAllen K, Matta SG, Sharp BM (2000) Expression of delta opioid receptors by splenocytes from SEB-treated mice and effects on phosphorylation of MAP kinase. Cell Immunol 205:84–93
Sharma SK, Klee WA, Nirenberg M (1975) Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance. Proc Natl Acad Sci USA 72:3092–3096
Sharp BM (2003) Opioid receptor expression and intracellular signaling by cells involved in host defense and immunity. Adv Exp Med Biol 521:98–105
Sheng WS, Hu S, Lokensgard JR, Peterson PK (2003) U50,488 inhibits HIV-1 Tat-induced monocyte chemoattractant protein-1 (CCL2) production by human astrocytes. Biochem Pharmacol 65:9–14
Sibinga NE, Goldstein A (1988) Opioid peptides and opioid receptors in cells of the immune system. Annu Rev Immunol 6:219–249
Smart D, Hirst RA, Hirota K, Grandy DK, Lambert DG (1997) The effects of recombinant rat mu-opioid receptor activation in CHO cells on phospholipase C, [Ca2+]i and adenylyl cyclase. Br J Pharmacol 120:1165–1171
Sofroniew MV, Howe CL, Mobley WC (2001) Nerve growth factor signaling, neuroprotection, and neural repair. Annu Rev Neurosci 24:1217–1281
Standifer KM, Pasternak GW (1997) G proteins and opioid receptor-mediated signalling. Cell Signal 9:237–248
Stefano GB, Hartman A, Bilfinger TV, Magazine HI, Liu Y, Casares F, Goligorsky MS (1995) Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric oxide production and vasodilation. J Biol Chem 270:30290–30293
Stein C, Hassan AH, Przewlocki R, Gramsch C, Peter K, Herz A (1990) Opioids from immunocytes interact with receptors on sensory nerves to inhibit nociception in inflammation. Proc Natl Acad Sci USA 87:5935–5939
Sun P, Loh HH (2002) Transcriptional regulation of mouse delta-opioid receptor gene. Role of Ikaros in the stimulated transcription of mouse delta-opioid receptor gene in activated T cells. J Biol Chem 277:12854–12860
Suzuki S, Chuang TK, Chuang LF, Doi RH, Chuang RY (2001) Morphine upregulates kappa-opioid receptors of human lymphocytes. Adv Exp Med Biol 493:81–87
Tallent M, Dichter MA, Bell GI, Reisine T (1994) The cloned kappa opioid receptor couples to an N-type calcium current in undifferentiated PC-12 cells. Neuroscience 63:1033–1040
Taylor DA, Fleming WW (2001) Unifying perspectives of the mechanisms underlying the development of tolerance and physical dependence to opioids. J Pharmacol Exp Ther 297:11–18
Viatour P, Merville MP, Bours V, Chariot A (2005) Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci 30:43–52
Walker JS (2003) Anti-inflammatory effects of opioids. Adv Exp Med Biol 521:148–160
Wang J, Barke RA, Charboneau R, Loh HH, Roy S (2003) Morphine negatively regulates interferon-gamma promoter activity in activated murine T cells through two distinct cyclic AMP-dependent pathways. J Biol Chem 278:37622–37631
Wang X, Douglas SD, Commons KG, Pleasure DE, Lai J, Ho C, Bannerman P, Williams M, Ho W (2004) A non-peptide substance P antagonist (CP-96,345) inhibits morphine-induced NF-kappa B promoter activation in human NT2-N neurons. J Neurosci Res 75:544–553
Wang L, Reinach P, Lu L (2005) TNF-alpha promotes cell survival through stimulation of K+ channel and NFkappaB activity in corneal epithelial cells. Exp Cell Res 311:39–48
Welters ID, Fimiani C, Bilfinger TV, Stefano GB (2000a) NF-kappaB, nitric oxide and opiate signaling. Med Hypotheses 54:263–268
Welters ID, Menzebach A, Goumon Y, Cadet P, Menges T, Hughes TK, Hempelmann G, Stefano GB (2000b) Morphine inhibits NF-kappaB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism. Anesthesiology 92:1677–1684
Williams JT, Christie MJ, Manzoni O (2001) Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev 81:299–343
Wong YH, Federman A, Pace AM, Zachary I, Evans T, Pouyssegur J, Bourne HR (1991) Mutant alpha subunits of Gi2 inhibit cyclic AMP accumulation. Nature 351:63–65
Wooten MW, Vandenplas ML, Seibenhener ML, Geetha T, Diaz-Meco MT (2001) Nerve growth factor stimulates multisite tyrosine phosphorylation and activation of the atypical protein kinase C's via a src kinase pathway. Mol Cell Biol 21:8414–8427
Yang J, Lin Y, Guo Z, Cheng J, Huang J, Deng L, Liao W, Chen Z, Liu Z, Su B (2001) The essential role of MEKK3 in TNF-induced NF-kappaB activation. Nat Immunol 2:620–624
Yasuda K, Raynor K, Kong H, Breder CD, Takeda J, Reisine T, Bell GI (1993) Cloning and functional comparison of kappa and delta opioid receptors from mouse brain. Proc Natl Acad Sci USA 90: 6736–6740
Ye RD (2001) Regulation of nuclear factor kappaB activation by G-protein-coupled receptors. J Leukoc Biol 70:839–848
Yeh SH, Lin CH, Lee CF, Gean PW (2002) A requirement of nuclear factor-kappaB activation in fear-potentiated startle. J Biol Chem 277:46720–46729
Yeiser EC, Rutkoski NJ, Naito A, Inoue J, Carter BD (2004) Neurotrophin signaling through the p75 receptor is deficient in traf6-/- mice. J Neurosci 24:10521–10529
Yuan J, Yankner BA (2000) Apoptosis in the nervous system. Nature 407:802–809
Zadina JE, Hackler L, Ge LJ, Kastin AJ (1997) A potent and selective endogenous agonist for the mu-opiate receptor. Nature 386:499–502
Zhang N, Oppenheim JJ (2005) Crosstalk between chemokines and neuronal receptors bridges immune and nervous systems. J Leukoc Biol 78:1210–1214
Zhang T, Li Y, Lai JP, Douglas SD, Metzger DS, O'Brien CP, Ho WZ (2003) Alcohol potentiates hepatitis C virus replicon expression. Hepatology 38:57–65
Zhong H, May MJ, Jimi E, Ghosh S (2002) The phosphorylation status of nuclear NF-kappa B determines its association with CBP/p300 or HDAC-1. Mol Cell 9:625–636
Zhu Y, Hsu MS, Pintar JE (1998) Developmental expression of the mu, kappa, and delta opioid receptor mRNAs in mouse. J Neurosci 18:2538–2549
Acknowledgements
This work was supported by National Institute of Health Grants DA000564, DA001583, DA011806, DA007339, DA016674, K05-DA70554 (HHL), and K05-DA00513 (PYL), and by the A. & F. Stark Fund of the Minnesota Medical Foundation.
We apologize to many authors whose contributions could not be discussed or whose primary references could not be cited in this review due to space limitation. We also thank Susan Marriott for editorial assistance in preparation of the abstract of this revised manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, Y.L., Law, PY. & Loh, H.H. Nuclear Factor κB Signaling in Opioid Functions and Receptor Gene Expression. Jrnl Neuroimmune Pharm 1, 270–279 (2006). https://doi.org/10.1007/s11481-006-9028-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11481-006-9028-0