The “Toll” of Opioid-Induced Glial Activation: Improving the Clinical Efficacy of Opioids by Targeting Glia

ATP mediates rapid microglial response to local brain injury in vivo

Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913

DAMPs, PAMPs and alarmins: all we need to know about danger

Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794

Pathological and protective roles of glia in chronic pain

Milligan, E. D., & Watkins, L. R. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2533 · Cited by 1,443

Inhibition of Microglial Activation Attenuates the Development but Not Existing Hypersensitivity in a Rat Model of Neuropathy

Vasudeva, R., Tanga, F. Y., & DeLeo, J. A. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.052407 · Cited by 797

Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation

Ledeboer, A., Sloane, E. M., Milligan, E. D., Frank, M. G., Mahony, J. H., Maier, S. F., & Watkins, L. R. (2005) · Pain · doi:10.1016/j.pain.2005.02.009 · Cited by 677

GLIA: A novel drug discovery target for clinical pain

Watkins, L. R., & Maier, S. F. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1251 · Cited by 674

Nociceptors Are Interleukin-1β Sensors

Binshtok, A. M., Wang, H., Zimmermann, K., Amaya, F., Vardeh, D., Shi, L., Brenner, G. J., Ji, R., Bean, B. P., Woolf, C. J., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3795-08.2008 · Cited by 664

The CNS role of Toll-like receptor 4 in innate neuroimmunity and painful neuropathy

Tanga, F. Y., Nutile-McMenemy, N., & DeLeo, J. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501634102 · Cited by 634

Evidence that opioids may have toll-like receptor 4 and MD-2 effects

Hutchinson, M. R., Zhang, Y., Shridhar, M., Evans, J. H., Buchanan, M. M., Zhao, T. X., Slivka, P. F., Coats, B. D., Rezvani, N., Wieseler, J. L., et al. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.08.004 · Cited by 575

Tumor necrosis factor-α

Rock, C. S., & Lowry, S. F. (1991) · Journal of Surgical Research · doi:10.1016/0022-4804(91)90146-d · Cited by 506

Acute p38-Mediated Modulation of Tetrodotoxin-Resistant Sodium Channels in Mouse Sensory Neurons by Tumor Necrosis Factor-α

Jin, X., & Gereau, R. W. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3858-05.2006 · Cited by 488

Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain

Guo, W., Wang, H., Watanabe, M., Shimizu, K., Zou, S., LaGraize, S. C., Wei, F., Dubner, R. A., & Ren, K. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0176-07.2007 · Cited by 480

The Role of Spinal Neuroimmune Activation in Morphine Tolerance/Hyperalgesia in Neuropathic and Sham-Operated Rats

Vasudeva, R., Rutkowski, M. D., & DeLeo, J. A. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09980.2002 · Cited by 468

The involvement of glial cells in the development of morphine tolerance

Song, P., & Zhao, Z.-Q. (2001) · Neuroscience Research · doi:10.1016/s0168-0102(00)00226-1 · Cited by 445

A Role for Proinflammatory Cytokines and Fractalkine in Analgesia, Tolerance, and Subsequent Pain Facilitation Induced by Chronic Intrathecal Morphine

Johnston, I. N., Milligan, E. D., Wieseler‐Frank, J., Frank, M. G., Zapata, V., Campisi, J., Langer, S. J., Martin, D., Green, P., Fleshner, M., et al. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1850-04.2004 · Cited by 440

Non‐stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll‐like receptor 4 (TLR4)

Hutchinson, M. R., Zhang, Y., Brown, K., Coats, B. D., Shridhar, M., Sholar, P. W., Patel, S. J., Crysdale, N. Y., Harrison, J. A., Maier, S. F., et al. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06321.x · Cited by 399

Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward

Hutchinson, M. R., Bland, S. T., Johnson, K. W., Rice, K. C., Maier, S. F., & Watkins, L. R. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.230 · Cited by 359

TLR4/MyD88/PI3K interactions regulate TLR4 signaling.

Laird, M. H. W., Rhee, S. H., Perkins, D. J., Medvedev, A. E., Piao, W., Fenton, M. J., & Vogel, S. N. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1208763 · Cited by 342

Glia: novel counter-regulators of opioid analgesia

Watkins, L. R., Hutchinson, M. R., Johnston, I. N., & Maier, S. F. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.10.001 · Cited by 327

Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation

Wei, F., Guo, W., Zou, S., Ren, K., & Dubner, R. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3593-08.2008 · Cited by 322

A Critical Role of Toll-like Receptor 2 in Nerve Injury-induced Spinal Cord Glial Cell Activation and Pain Hypersensitivity

Kim, D., Kim, M. A., Cho, I., Kim, M. S., Lee, S., Jo, E., Choi, S., Park, K., Kim, J. S., Akira, S., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607277200 · Cited by 315

Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats

Ledeboer, A., Jekich, B. M., Sloane, E. M., Mahoney, J. H., Langer, S. J., Milligan, E. D., Martin, D., Maier, S. F., Johnson, K. W., Leinwand, L. A., et al. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.10.012 · Cited by 310

Proinflammatory cytokines oppose opioid-induced acute and chronic analgesia

Hutchinson, M. R., Coats, B. D., Lewis, S. S., Zhang, Y., Sprunger, D. B., Rezvani, N., Baker, E. M., Jekich, B. M., Wieseler, J. L., Somogyi, A. A., et al. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.05.004 · Cited by 307

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

Hutchinson, M. R., Lewis, S. S., Coats, B. D., Skyba, D. A., Crysdale, N. Y., Berkelhammer, D. L., Brzeski, A., Northcutt, A. L., Vietz, C. M., Judd, C. M., et al. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.09.012 · Cited by 306

Microglia and neuropathic pain

Inoue, K., & Tsuda, M. (2009) · Glia · doi:10.1002/glia.20871 · Cited by 294

Minocycline and pentoxifylline attenuate allodynia and hyperalgesia and potentiate the effects of morphine in rat and mouse models of neuropathic pain

Mika, J., Osikowicz, M., Makuch, W., & Przewłocka, B. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.01.013 · Cited by 291

Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats

Raghavendra, V., Tanga, F. Y., & DeLeo, J. A. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300315 · Cited by 263

Potentiation of Opiate Analgesia and Apparent Reversal of Morphine Tolerance by Proglumide

Watkins, L. R., Kinscheck, I. B., & Mayer, D. J. (1984) · Science · doi:10.1126/science.6546809 · Cited by 259

Spinal glial activation contributes to pathological pain states

Cao, H., & Zhang, Y. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.03.009 · Cited by 248

Comparative Evaluation of the Translocator Protein Radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a Rat Model of Acute Neuroinflammation

Chauveau, F., Camp, N. V., Dollé, F., Kühnast, B., Hinnen, F., Damont, A., Boutin, H., James, M. L., Kassiou, M., & Tavitian, B. (2009) · Journal of Nuclear Medicine · doi:10.2967/jnumed.108.058669 · Cited by 236

Role of spinal microglia in rat models of peripheral nerve injury and inflammation

Clark, A. K., Gentry, C., Bradbury, E. J., McMahon, S. B., & Malcangio, M. (2006) · European Journal of Pain · doi:10.1016/j.ejpain.2006.02.003 · Cited by 235

Contribution of the activation of satellite glia in sensory ganglia to pathological pain

Takeda, M., Takahashi, M., & Matsumoto, S. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.12.005 · Cited by 227

Morphine Enhances Microglial Migration through Modulation of P2X4Receptor Signaling

Horvath, R. J., & DeLeo, J. A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4595-08.2009 · Cited by 219

Direct Evidence of Astrocytic Modulation in the Development of Rewarding Effects Induced by Drugs of Abuse

Narita, M., Miyatake, M., Narita, M., Shibasaki, M., Shindo, K., Nakamura, A., Kuzumaki, N., Nagumo, Y., & Suzuki, T. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301007 · Cited by 218

Controlling pathological pain by adenovirally driven spinal production of the anti‐inflammatory cytokine, interleukin‐10

Milligan, E. D., Langer, S. J., Sloane, E. M., He, L., Wieseler‐Frank, J., O’Connor, K., Martin, D., Forsayeth, J., Maier, S. F., Johnson, K. W., et al. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04057.x · Cited by 217

Opioid Tolerance and Hyperalgesia

Chang, G., Chen, L. L., & Mao, J. (2007) · Medical Clinics of North America · doi:10.1016/j.mcna.2006.10.003 · Cited by 210

A novel role of minocycline: Attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia

Cui, Y., Liao, X., Liu, W., Guo, R., Wu, Z.-Z., Zhao, C., Chen, P., & Feng, J. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.07.014 · Cited by 207

“Listening” and “talking” to neurons: implications of immune activation for pain control and increasing the efficacy of opioids

Watkins, L. R., Hutchinson, M. R., Milligan, E. D., & Maier, S. F. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.06.006 · Cited by 185

Modulation of microglia can attenuate neuropathic pain symptoms and enhance morphine effectiveness.

Mika, J. (2008) · PubMed · Cited by 184

IL-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats

Zhang, R.-X., Li, A., Liu, B., Wang, L., Ren, K., Zhang, H., Berman, B., & Lao, L. (2007) · Pain · doi:10.1016/j.pain.2007.05.023 · Cited by 183

Controlling Neuropathic Pain by Adeno-Associated Virus Driven Production of the Anti-Inflammatory Cytokine, Interleukin-10

Milligan, E. D., Sloane, E. M., Langer, S. J., Cruz, P. E., Chacur, M., Spataro, L. E., Wieseler‐Frank, J., Hammack, S. E., Maier, S. F., Flotte, T. R., et al. (2005) · Molecular Pain · doi:10.1186/1744-8069-1-9 · Cited by 181

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

Hutchinson, M. R., Northcutt, A. L., Chao, L. W., Kearney, J. J., Zhang, Y., Berkelhammer, D. L., Loram, L. C., Rozeske, R. R., Bland, S. T., Maier, S. F., et al. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.07.008 · Cited by 180

Interleukin-1 antagonizes morphine analgesia and underlies morphine tolerance

Shavit, Y., Wolf, G., Goshen, I., Livshits, D., & Yirmiya, R. (2005) · Pain · doi:10.1016/j.pain.2005.02.003 · Cited by 176

Activation of p38 mitogen-activated protein kinase in spinal microglia mediates morphine antinociceptive tolerance

Cui, Y., Chen, Y., Zhi, J., Guo, R., Feng, J., & Chen, P. (2006) · Brain Research · doi:10.1016/j.brainres.2005.11.066 · Cited by 173

Effects of Etanercept and Minocycline in a rat model of spinal cord injury

Marchand, F., Tsantoulas, C., Singh, D., Grist, J., Clark, A. K., Bradbury, E. J., & McMahon, S. B. (2008) · European Journal of Pain · doi:10.1016/j.ejpain.2008.08.001 · Cited by 169

Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury

Romero-Sandoval, A., Nutile-McMenemy, N., & DeLeo, J. A. (2008) · Anesthesiology · doi:10.1097/aln.0b013e318167af74 · Cited by 168

Attenuation of morphine tolerance by minocycline and pentoxifylline in naive and neuropathic mice

Mika, J., Wawrzczak‐Bargieła, A., Osikowicz, M., Makuch, W., & Przewłocka, B. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.07.005 · Cited by 163

Ibudilast (AV-411)

Ledeboer, A., Hutchinson, M. R., Watkins, L. R., & Johnson, K. W. (2007) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.16.7.935 · Cited by 153

The glial activation inhibitor AV411 reduces morphine-induced nucleus accumbens dopamine release

Bland, S. T., Hutchinson, M. R., Maier, S. F., Watkins, L. R., & Johnson, K. W. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.01.014 · Cited by 152

Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain patients

Backonja, M. “., Coe, C. L., Muller, D. A., & Schell, K. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.01.005 · Cited by 149

Propentofylline attenuates allodynia, glial activation and modulates GABAergic tone after spinal cord injury in the rat

Gwak, Y. S., Crown, E. D., Unabia, G. C., & Hulsebosch, C. E. (2008) · Pain · doi:10.1016/j.pain.2008.01.021 · Cited by 143

Tumor necrosis factor-α induces long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn in rats with nerve injury: The role of NF-kappa B, JNK and p38 MAPK

Liu, Y., Zhou, L., Hu, N., Xu, J., Wu, C. Y., Zhang, T., Li, Y.-Y., & Liu, X. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2006.09.011 · Cited by 142

Neuroimmune interactions and pain: focus on glial-modulating targets.

Romero-Sandoval, E. A., Horvath, R. J., & DeLeo, J. A. (2008) · PubMed · Cited by 140

Spinal cord histopathological alterations in a patient with longstanding complex regional pain syndrome

Valle, L. D., Schwartzman, R. J., & Alexander, G. M. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.08.004 · Cited by 139

Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury

Tawfik, V. L., Nutile‐McMenemy, N., LaCroix‐Fralish, M. L., & DeLeo, J. A. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.07.001 · Cited by 136

Minocycline prevents the development of neuropathic pain, but not acute pain: Possible anti-inflammatory and antioxidant mechanisms

Padi, S. S. V., & Kulkarni, S. K. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.10.018 · Cited by 134

Ceramide-induced activation of NADPH oxidase and endothelial dysfunction in small coronary arteries

Zhang, D. X., Zou, A.-P., & Li, P. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00697.2002 · Cited by 124

Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury

Banati, R. B., Cagnin, A., Brooks, D. J., Gunn, R. N., Myers, R., Jones, T., Birch, R., & Anand, P. (2001) · Neuroreport · doi:10.1097/00001756-200111160-00012 · Cited by 123

Spinal Cannabinoid Receptor Type 2 Activation Reduces Hypersensitivity and Spinal Cord Glial Activation after Paw Incision

Romero-Sandoval, A. E., & Eisenach, J. C. (2007) · Anesthesiology · doi:10.1097/01.anes.0000264765.33673.6c · Cited by 122

The glial modulatory drug AV411 attenuates mechanical allodynia in rat models of neuropathic pain

Ledeboer, A., Liu, T., Shumilla, J. A., Mahoney, J. H., Vijay, S., Gross, M. I., Vargas, J. A., Sultzbaugh, L., Claypool, M. D., Sanftner, L. M., et al. (2006) · Neuron Glia Biology · doi:10.1017/s1740925x0700035x · Cited by 122

The contributing role of CD14 in toll-like receptor 4 dependent neuropathic pain

Cao, L., Tanga, F. Y., & DeLeo, J. A. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.004 · Cited by 114

Mechanisms underlying morphine analgesic tolerance and dependence

Ueda, H. (2009) · Frontiers in bioscience · doi:10.2741/3596 · Cited by 109

Anti-inflammatory cytokine gene therapy decreases sensory and motor dysfunction in experimental Multiple Sclerosis: MOG-EAE behavioral and anatomical symptom treatment with cytokine gene therapy

Sloane, E. M., Ledeboer, A., Seibert, W., Coats, B. D., van Strien, M. E., Maier, S. F., Johnson, K. W., Chavez, R. A., Watkins, L. R., Leinwand, L. A., et al. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.09.004 · Cited by 105

Changes in immune and glial markers in the CSF of patients with Complex Regional Pain Syndrome

Alexander, G. M., Perreault, M. J., Reichenberger, E. R., & Schwartzman, R. J. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.10.009 · Cited by 105

Astrocytic control of synaptic transmission and plasticity: a target for drugs of abuse?

Haydon, P. G., Blendy, J. A., Moss, S. J., & Jackson, F. R. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.06.050 · Cited by 103

The effects of thalidomide and minocycline on taxol-induced hyperalgesia in rats

Cata, J. P., Weng, H., & Dougherty, P. M. (2008) · Brain Research · doi:10.1016/j.brainres.2008.07.001 · Cited by 102

Morphine-induced macrophage apoptosis: oxidative stress and strategies for modulation

Bhat, R. S., Bhaskaran, M. C., Mongia, A. K., Hitosugi, N., & Singhal, P. C. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.1203639 · Cited by 99

Activation of interleukin‐1β receptor suppresses the voltage‐gated potassium currents in the small‐diameter trigeminal ganglion neurons following peripheral inflammation

Takeda, M., Kitagawa, J., Takahashi, M., & Matsumoto, S. (2008) · Pain · doi:10.1016/j.pain.2008.06.015 · Cited by 98

Morphine-Induced Chemotaxis and Brain-Derived Neurotrophic Factor Expression in Microglia

Takayama, N., & Ueda, H. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3170-04.2005 · Cited by 97

A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833

Whiteside, G. T., Gottshall, S. L., Boulet, J. M., Chaffer, S. M., Harrison, J., Pearson, M. S., Turchin, P. I., Mark, L., Garrison, A. E., & Valenzano, K. J. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.10.043 · Cited by 94

Glial activation in the rostroventromedial medulla promotes descending facilitation to mediate inflammatory hypersensitivity

Roberts, J., Ossipov, M. H., & Porreca, F. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06813.x · Cited by 89

Activation of microglia and p38 mitogen-activated protein kinase in the dorsal column nucleus contributes to tactile allodynia following peripheral nerve injury

Terayama, R., Omura, S., Fujisawa, N., Yamaai, T., Ichikawa, H., & Sugimoto, T. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.03.041 · Cited by 88

Evidence for a role of heat shock protein-90 in toll like receptor 4 mediated pain enhancement in rats

Hutchinson, M. R., Ramos, K. M., Loram, L. C., Wieseler, J. L., Sholar, P. W., Kearney, J. J., Lewis, M. T., Crysdale, N. Y., Zhang, Y., Harrison, J. A., et al. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.09.046 · Cited by 87

MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models

Naguib, M., Diaz, P., Xu, J. J., Astruc‐Diaz, F., Craig, S., Vivas‐Mejia, P., & Brown, D. L. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.340 · Cited by 82

Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain

Liu, J., Feng, X., Yu, M., Xie, W., Zhao, X., Li, W., Guan, R., & Xu, J. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.11.022 · Cited by 82

Microglial NADPH oxidase is a novel target for femtomolar neuroprotection against oxidative stress

Qin, L., Block, M. L., Liu, Y., Bienstock, R. J., Pei, Z., Zhang, W., Wu, X., Wilson, B. C., Burka, T., & Hong, J. (2005) · The FASEB Journal · doi:10.1096/fj.04-2857com · Cited by 81

Interleukin 1β facilitates bone cancer pain in rats by enhancing NMDA receptor NR-1 subunit phosphorylation

Zhang, R.-X., Liu, B., Li, A., Wang, L., Ren, K., Qiao, J.-T., Berman, B., & Lao, L. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.04.072 · Cited by 81

Acid Sphingomyelinase Is Required for Lipid Raft TLR4 Complex Formation

Cuschieri, J., Bulger, E. M., Billgrin, J., Garcia, I. A., & Maier, R. V. (2007) · Surgical Infections · doi:10.1089/sur.2006.050 · Cited by 80

Differential regulation of microglial activation by propentofylline via cAMP signaling

Si, Q., Nakamura, Y., Ogata, T., Kataoka, K., & Schubert, P. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00954-8 · Cited by 79

Propentofylline attenuates vincristine-induced peripheral neuropathy in the rat

Sweitzer, S. M., Pahl, J. L., & DeLeo, J. A. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.02.058 · Cited by 77

Nociception increases during opioid infusion in opioid receptor triple knock-out mice

Juni, A., Klein, G. E., Pintar, J. E., & Kest, B. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.04.030 · Cited by 75

Spinal Ceramide Modulates the Development of Morphine Antinociceptive Tolerance via Peroxynitrite-Mediated Nitroxidative Stress and Neuroimmune Activation

Ndengele, M. M., Cuzzocrea, S., Masini, E., Vinci, M. C., Esposito, E., Muscoli, C., Petrusca, D. N., Mollace, V., Mazzon, E., Li, D., et al. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.146290 · Cited by 72

Implication of Activated Astrocytes in the Development of Drug Dependence

Narita, M., Suzuki, M., Kuzumaki, N., Miyatake, M., & Suzuki, T. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1441.032 · Cited by 72

Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome

Wei, T., Sabsovich, I., Guo, T., Shi, X., Zhao, R., Li, W., Geis, C., Sommer, C., Kingery, W. S., & Clark, J. D. (2008) · European Journal of Pain · doi:10.1016/j.ejpain.2008.04.014 · Cited by 67

A novel method for modeling facial allodynia associated with migraine in awake and freely moving rats

Wieseler, J. L., Ellis, A., Sprunger, D. B., Brown, K., McFadden, A., Mahoney, J. H., Rezvani, N., Maier, S. F., & Watkins, L. R. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.10.006 · Cited by 65

IL-1β signaling is required for mechanical allodynia induced by nerve injury and for the ensuing reduction in spinal cord neuronal GRK2

Kleibeuker, W., Gabay, E., Kavelaars, A., Zijlstra, J., Wolf, G., Ziv, N., Yirmiya, R., Shavit, Y., Tal, M., & Heijnen, C. J. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.07.009 · Cited by 64

The Paths of Pain: 1975-2005

Merskey, H., Loeser, J. D., & Dubner, R. A. (2005) · Medical Entomology and Zoology · Cited by 62

Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-α production via down-regulation of MyD88 expression

Noman, A. S. M., Koide, N., Hassan, F., Iftakhar-E-Khuda, I., Dagvadorj, J., Tumurkhuu, G., Islam, S., Naiki, Y., Yoshida, T., & Yokochi, T. (2009) · Innate Immunity · doi:10.1177/1753425908099317 · Cited by 62

Interleukin-1 signaling is required for induction and maintenance of postoperative incisional pain: Genetic and pharmacological studies in mice

Wolf, G., Livshits, D., Beilin, B., Yirmiya, R., & Shavit, Y. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.03.005 · Cited by 60

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Tawfik, V. L., LaCroix‐Fralish, M. L., Nutile‐McMenemy, N., & DeLeo, J. A. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.082420 · Cited by 60

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Chacur, M., Lambertz, D., Hoheisel, U., & Mense, S. (2008) · European Journal of Pain · doi:10.1016/j.ejpain.2008.11.008 · Cited by 58

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Early microglial inhibition preemptively mitigates chronic pain development after experimental spinal cord injury.

Tan, A. M., Zhao, P., Waxman, S. G., & Hains, B. C. (2009) · PubMed · Cited by 50

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Association of IL-1B genetic polymorphisms with an increased risk of opioid and alcohol dependence

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Wang, S., Lim, G., Mao, J., Sung, B., & Mao, J. (2008) · Pain · doi:10.1016/j.pain.2008.10.021 · Cited by 31

Stereoselective action of (+)-morphine over (−)-morphine in attenuating the (−)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse

Wu, H.-E., Hong, J., & Tseng, L. F. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.06.012 · Cited by 31

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Wu, H.-E., Thompson, J., Sun, H.-S., Terashvili, M., & Tseng, L. F. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.087130 · Cited by 30

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Rothman, S. M., Guarino, B. B., & Winkelstein, B. A. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22090 · Cited by 28

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Yoon, H. J., Jeon, S. B., Suk, K., Choi, D., Hong, Y., & Park, E. J. (2008) · Molecules and Cells · doi:10.1016/s1016-8478(23)17556-x · Cited by 21

dextro- and levo-morphine attenuate opioid δ and κ receptor agonist produced analgesia in μ-opioid receptor knockout mice

Wu, H.-E., Sun, H.-S., Terashivili, M., Schwasinger, E. T., Sora, I., Hall, F. S., Uhl, G. R., & Tseng, L. F. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.12.012 · Cited by 19

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Li, A., Lao, L., Wang, Y., Zhang, H., Ren, K., Berman, B., & Zhang, R.-X. (2007) · Neuroreport · doi:10.1097/wnr.0b013e3280586839 · Cited by 7

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Ji, R., Berta, T., & Nedergaard, M. (2013) · Pain · doi:10.1016/j.pain.2013.06.022 · Cited by 1,193

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Hutchinson, M. R., Bland, S. T., Johnson, K. W., Rice, K. C., Maier, S. F., & Watkins, L. R. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.230 · Cited by 359

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Watkins, L. R. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.84.3

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