Cited by 166Pain Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNeuropeptides and Animal Physiology

The DOI matches its Crossref record; 94 of the 96 references it cites were found in a registry or an index.

Sex Differences in Microglia Activity within the Periaqueductal Gray of the Rat: A Potential Mechanism Driving the Dimorphic Effects of Morphine

Open access

Doyle, Hillary H., Eidson, Lori N., Sinkiewicz, David M., Murphy, Anne Z.·2017·The Journal of Neuroscience

DOI 10.1523/jneurosci.2906-16.2017PMC PMC5373114

Open this paper in CoChat — free account Open PDF

Abstract

Although morphine remains the primary drug prescribed for alleviation of severe or persistent pain, both preclinical and clinical studies have shown that females require two to three times more morphine than males to produce comparable levels of analgesia. In addition to binding to the neuronal μ-opioid receptor, morphine binds to the innate immune receptor toll-like receptor 4 (TLR4) localized primarily on microglia. Morphine action at TLR4 initiates a neuroinflammatory response that directly opposes the analgesic effects of morphine. Here, we test the hypothesis that the attenuated response to morphine observed in females is the result of increased microglia activation in the periaqueductal gray (PAG), a central locus mediating the antinociceptive effects of morphine. We report that, whereas no overall sex differences in the density of microglia were noted within the PAG of male or female rats, microglia exhibited a more “activated” phenotype in females at baseline, with the degree of activation a significant predictor of morphine half-maximal antinociceptive dose (ED50) values. Priming microglia with LPS induced greater microglia activation in the PAG of females compared with males and was accompanied by increased transcription levels of IL-1β and a significant rightward shift in the morphine dose–response curve. Blockade of morphine binding to PAG TLR4 with (+)-naloxone potentiated morphine antinociception significantly in females such that no sex differences in ED50were observed. These results demonstrate that PAG microglia are sexually dimorphic in both basal and LPS-induced activation and contribute to the sexually dimorphic effects of morphine in the rat. SIGNIFICANCE STATEMENTWe demonstrate that periaqueductal gray (PAG) microglia contribute to the sexually dimorphic effects of morphine. Specifically, we report that increased activation of microglia in the PAG contributes to the attenuated response to morphine observed in females. Our data further implicate the innate immune receptor toll-like receptor 4 (TLR4) as an underlying mechanism mediating these effects and establish that TLR4 inhibition in the PAG of females reverses the sex differences in morphine responsiveness. These data suggest novel methods to improve current opioid-based pain management via inhibition of glial TLR4 and illustrate the necessity for sex-specific research and individualized treatment strategies for the management of pain in men and women.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1523/jneurosci.2906-16.2017

Cites

94 of 94 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016
Dowell, D., Haegerich, T. M., & Chou, R. (2016) · JAMA · doi:10.1001/jama.2016.1464 · Cited by 5,161
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Hargreaves, K., Dubner, R. A., Brown, F. J., Flores, C., & Joris, J. L. (1988) · Pain · doi:10.1016/0304-3959(88)90026-7 · Cited by 5,155
Physiology of Microglia
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
The two NF-κB activation pathways and their role in innate and adaptive immunity
Bonizzi, G., & Karin, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.03.008 · Cited by 2,535
Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration
Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R., Hong, J., Knapp, D. J., & Crews, F. T. (2007) · Glia · doi:10.1002/glia.20467 · Cited by 2,144
Different immune cells mediate mechanical pain hypersensitivity in male and female mice
Sorge, R. E., Mapplebeck, J. C. S., Rosen, S., Beggs, S., Taves, S., Alexander, J. K., Martin, L. J., Austin, J.-S., Sotocinal, S. G., Chen, D., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4053 · Cited by 1,442
Sex differences in autoimmune disease
Whitacre, C. C. (2001) · Nature Immunology · doi:10.1038/ni0901-777 · Cited by 1,294
Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway
Lehnardt, S., Massillon, L., Follett, P., Jensen, F. E., Ratan, R., Rosenberg, P. A., Volpe, J. J., & Vartanian, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432609100 · Cited by 1,052
Differential Regulation of AMPA Receptor and GABA Receptor Trafficking by Tumor Necrosis Factor-α
Stellwagen, D., Beattie, E. C., Seo, J. Y., & Malenka, R. C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4486-04.2005 · Cited by 985 · cited 2×
“…increases neuronal excitability via upregulation of the -amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (Ogoshi et al., 2005; Stellwagen et al., 2005), downregulation of glutamate transporter (Yan et al., 2014; Eidson et al., 2017), and decreased -aminobutyric acid (GABAA)…”
Background
A Gender Gap in Autoimmunity: Task Force on Gender, Multiple Sclerosis and Autoimmunity
Whitacre, C. C., Reingold, S. C., O'Looney, P. A., Blankenhorn, E., Brinley, F., Collier, E., Duquette, P., Fox, H., Giesser, B., Gilmore, W., et al. (1999) · Science · doi:10.1126/science.283.5406.1277 · Cited by 851

Show all 96 references

Sorted by citations

Qualitative sex differences in pain processing: emerging evidence of a biased literature
Mogil, J. S. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0310-6 · Cited by 691
Considering sex as a biological variable will require a global shift in science culture
Shansky, R. M., & Murphy, A. Z. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00806-8 · Cited by 442
Self-citation
Microglia morphophysiological diversity and its implications for the CNS
Vidal-Itriago, A., Radford, R. A. W., Aramideh, J. A., Maurel, C., Scherer, N. M., Don, E. K., Lee, A., Chung, R. S., Graeber, M. B., & Morsch, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.997786 · Cited by 451
Sexual dimorphism in the inflammatory response to traumatic brain injury
Villapol, S., Loane, D. J., & Burns, M. P. (2017) · Glia · doi:10.1002/glia.23171 · Cited by 320
Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action
Caylor, J. R., Reddy, R. D., Yin, S., Cui, C. L., Huang, M., Huang, C. W., Rao, R., Baker, D. G., Simmons, A. N., Souza, D., et al. (2019) · Bioelectronic Medicine · doi:10.1186/s42234-019-0023-1 · Cited by 251
Uncovering sex differences of rodent microglia
Han, J., Fan, Y., Zhou, K., Blomgren, K., & Harris, R. A. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02124-z · Cited by 224
Pathology of pain and its implications for therapeutic interventions
Cao, B., Xu, Q., Shi, Y., Zhao, R., Li, H., Zheng, J., Liu, F., Wan, Y., & Wei, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01845-w · Cited by 236
Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice
Huffman, W. J., Subramaniyan, S., Rodriguiz, R. M., Wetsel, W. C., Grill, W. M., & Terrando, N. (2019) · Brain Stimulation · doi:10.1016/j.brs.2018.10.005 · Cited by 181
Sex- and Gender-Based Pharmacological Response to Drugs
Mauvais‐Jarvis, F., Berthold, H. K., Campesi, I., Carrero, J. J., Dhakal, S., Franconi, F., Gouni‐Berthold, I., Heiman, M. L., Kautzky‐Willer, A., Klein, S. L., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000206 · Cited by 203
Self-citation
Sex differences and the endocannabinoid system in pain
Blanton, H. L., Barnes, R. C., McHann, M. C., Bilbrey, J. A., Wilkerson, J. L., & Guindon, J. (2021) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2021.173107 · Cited by 151
Neuroinflammation: The central enabler of postoperative cognitive dysfunction
Liu, Y., Yang, W., Xue, J., Chen, J., Liu, S., Zhang, S., Zhang, X., Gu, X., Dong, Y., & Qiu, P. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115582 · Cited by 139
Sex differences in neuroimmune and glial mechanisms of pain
Gregus, A. M., Levine, I. S., Eddinger, K. A., Yaksh, T. L., & Buczynski, M. W. (2021) · Pain · doi:10.1097/j.pain.0000000000002215 · Cited by 137
Microglia Control Escalation of Drinking in Alcohol-Dependent Mice: Genomic and Synaptic Drivers
Warden, A. S., Wolfe, S. A., Khom, S., Varodayan, F. P., Patel, R. R., Steinman, M. Q., Bajo, M., Montgomery, S. E., Vlkolinský, R., Nadav, T., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.05.011 · Cited by 123
Neuroinflammatory priming to stress is differentially regulated in male and female rats
Fonken, L. K., Frank, M. G., Gaudet, A. D., D’Angelo, H. M., Daut, R. A., Hampson, E. C., Ayala, M. T., Watkins, L. R., & Maier, S. F. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.03.005 · Cited by 119
“Bridging the Gap” Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era
Gemmati, D., Varani, K., Bramanti, B., Piva, R., Bonaccorsi, G., Trentini, A., Manfrinato, M. C., Tisato, V., Carè, A., & Bellini, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010296 · Cited by 120
Periaqueductal gray/dorsal raphe dopamine neurons contribute to sex differences in pain-related behaviors
Yu, W., Pati, D., Pina, M. M., Schmidt, K. T., Boyt, K. M., Hunker, A. C., Zweifel, L. S., McElligott, Z. A., & Kash, T. L. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.001 · Cited by 112
Periaqueductal Gray Sheds Light on Dark Areas of Psychopathology
George, D. T., Ameli, R., & Koob, G. F. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.03.004 · Cited by 108
Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease
Prakash, P., Manchanda, P., Paouri, E., Bisht, K., Sharma, K., Rajpoot, J., Wendt, V., Hossain, A., Wijewardhane, P. R., Randolph, C. E., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.029 · Cited by 104
Sex differences in pain and opioid mediated antinociception: Modulatory role of gonadal hormones.
Nasser, S. A., & Afify, E. A. (2019) · Life Science · doi:10.1016/j.lfs.2019.116926 · Cited by 83
Neuronal and glial factors contributing to sex differences in opioid modulation of pain
Averitt, D. L., Eidson, L. N., Doyle, H. H., & Murphy, A. Z. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0127-4 · Cited by 95
Self-citation
The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury
Pottorf, T. S., Rotterman, T. M., McCallum, W. M., Haley-Johnson, Z., & Álvarez, F. J. (2022) · Cells · doi:10.3390/cells11132083 · Cited by 95
Sex differences in the neuroimmune system
Osborne, B. F., Turano, A., & Schwarz, J. M. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.05.007 · Cited by 90
Sensory Neurons, Neuroimmunity, and Pain Modulation by Sex Hormones
Lenert, M. E., Avona, A., Garner, K. M., Barron, L. R., & Burton, M. D. (2021) · Endocrinology · doi:10.1210/endocr/bqab109 · Cited by 97
The Dynamic Role of Microglia and the Endocannabinoid System in Neuroinflammation
Young, A. P., & Denovan‐Wright, E. M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.806417 · Cited by 92
Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats
Althammer, F., Ferreira‐Neto, H. C., Rubaharan, M., Roy, R. K., Patel, A. A., Murphy, A. Z., Cox, D. N., & Stern, J. E. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01892-4 · Cited by 94
Self-citation
Why the sexes don’t feel pain the same way
Dance, A. (2019) · Nature · doi:10.1038/d41586-019-00895-3 · Cited by 84
Sex differences in pain along the neuraxis
Presto, P., Mazzitelli, M., Junell, R., Griffin, Z., & Neugebauer, V. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109030 · Cited by 79
Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities
Namba, M. D., Leyrer-Jackson, J. M., Nagy, E. K., Olive, M. F., & Neisewander, J. L. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.650785 · Cited by 76
Microglia Express Mu Opioid Receptor: Insights From Transcriptomics and Fluorescent Reporter Mice
Maduna, T., Audouard, E., Dembélé, D., Mouzaoui, N., Reiss, D. J., Massotte, D., & Gavériaux‐Ruff, C. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00726 · Cited by 78
Increased pain sensitivity and decreased opioid analgesia in T-cell-deficient mice and implications for sex differences
Rosen, S. F., Ham, B., Haichin, M., Walters, I. C., Tohyama, S., Sotocinal, S. G., & Mogil, J. S. (2018) · Pain · doi:10.1097/j.pain.0000000000001420 · Cited by 79
Sex differences in pain responses
Sorge, R. E., & Strath, L. J. (2018) · Current Opinion in Physiology · doi:10.1016/j.cophys.2018.05.006 · Cited by 73
Morphine and Fentanyl Repeated Administration Induces Different Levels of NLRP3-Dependent Pyroptosis in the Dorsal Raphe Nucleus of Male Rats via Cell-Specific Activation of TLR4 and Opioid Receptors
Carranza‐Aguilar, C. J., Hernández-Mendoza, A., Mejías-Aponte, C. A., Rice, K. C., Morales, M., González‐Espinosa, C., & Cruz, S. L. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00957-5 · Cited by 73
Sex‐specific transcriptome of spinal microglia in neuropathic pain due to peripheral nerve injury
Fiore, N. T., Yin, Z., Güneykaya, D., Gauthier, C. D., Hayes, J. P., D’Hary, A., Butovsky, O., & Moalem‐Taylor, G. (2022) · Glia · doi:10.1002/glia.24133 · Cited by 73
Glial and neuroimmune cell choreography in sexually dimorphic pain signaling
Midavaine, É., Côté, J., Marchand, S., & Sarret, P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.01.023 · Cited by 68
Microglia and BDNF at the crossroads of stressor related disorders: Towards a unique trophic phenotype
Prowse, N. A., & Hayley, S. P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.018 · Cited by 72
Interactions of neuroimmune signaling and glutamate plasticity in addiction
Gipson, C. D., Rawls, S. M., Scofield, M. D., Siemsen, B. M., Bondy, E. O., & Maher, E. E. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02072-8 · Cited by 71
Women, opioid use and addiction
Goetz, T. G., Becker, J. B., & Mazure, C. M. (2021) · The FASEB Journal · doi:10.1096/fj.202002125r · Cited by 70
PACAP and migraine headache: immunomodulation of neural circuits in autonomic ganglia and brain parenchyma
Waschek, J. A., Baca, S. M., & Akerman, S. (2018) · The Journal of Headache and Pain · doi:10.1186/s10194-018-0850-6 · Cited by 65
Mu opioid receptor in microglia contributes to morphine analgesic tolerance, hyperalgesia, and withdrawal in mice
Reiss, D. J., Maduna, T., Maurin, H., Audouard, E., & Gavériaux‐Ruff, C. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24626 · Cited by 62
Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation
Crespo‐Castrillo, A., & Arévalo, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093219 · Cited by 65
Small cells with big implications: Microglia and sex differences in brain development, plasticity and behavioral health
Nelson, L. H., Saulsbery, A. I., & Lenz, K. M. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.09.002 · Cited by 62
Peripheral Mechanisms of Ischemic Myalgia
Queme, L. F., Ross, J. L., & Jankowski, M. P. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00419 · Cited by 57
Investigation of Sex Differences in the Microglial Response to Binge Ethanol and Exercise
Barton, E. A., Baker, C., & Leasure, J. L. (2017) · Brain Sciences · doi:10.3390/brainsci7100139 · Cited by 55
Sex differences in primary muscle afferent sensitization following ischemia and reperfusion injury
Ross, J. L., Queme, L. F., Lamb, J. E., Green, K. J., & Jankowski, M. P. (2018) · Biology of Sex Differences · doi:10.1186/s13293-017-0163-5 · Cited by 55
Impact of sex on pain and opioid analgesia: a review
Fullerton, E. F., Doyle, H. H., & Murphy, A. Z. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.08.001 · Cited by 55
Self-citation
Sex-Dependent Influences of Morphine and its Metabolites on Pain Sensitivity in the Rat
Doyle, H. H., & Murphy, A. Z. (2017) · Physiology and Behavior · doi:10.1016/j.physbeh.2017.11.030 · Cited by 47
Self-citation
Careful Breakthrough Cancer Pain Treatment through Rapid-Onset Transmucosal Fentanyl Improves the Quality of Life in Cancer Patients: Results from the BEST Multicenter Study
Cuomo, A., Cascella, M., Forte, C. A., Bimonte, S., Esposito, G., Santis, S. D., Cavanna, L., Fusco, F., Dauri, M., Natoli, S., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9041003 · Cited by 51
Brain region- and sex-specific transcriptional profiles of microglia
Barko, K., Shelton, M. A., Xue, X., Afriyie-Agyemang, Y., Puig, S., Freyberg, Z., Tseng, G. C., Logan, R. W., & Seney, M. L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.945548 · Cited by 56
Sex-Dependent Mechanisms of Chronic Pain: A Focus on Microglia and P2X4R
Halievski, K., Ghazisaeidi, S., & Salter, M. W. (2020) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.120.265017 · Cited by 51
Systems and Circuits Linking Chronic Pain and Circadian Rhythms
Warfield, A. E., Prather, J. F., & Todd, W. D. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.705173 · Cited by 49
NOD-like receptor protein 3 inflammasome drives postoperative mechanical pain in a sex-dependent manner
Cowie, A. M., Menzel, A. D., O’Hara, C. L., Lawlor, M. W., & Stucky, C. L. (2019) · Pain · doi:10.1097/j.pain.0000000000001555 · Cited by 50
Neuroimmunology of the female brain across the lifespan: Plasticity to psychopathology
Barrientos, R. M., Brunton, P. J., Lenz, K. M., Pyter, L. M., & Spencer, S. J. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.03.010 · Cited by 50
Sex differences and mechanisms of muscle pain
Queme, L. F., & Jankowski, M. P. (2019) · Current Opinion in Physiology · doi:10.1016/j.cophys.2019.03.006 · Cited by 48
Cannabinoids in the descending pain modulatory circuit: Role in inflammation
Bouchet, C. A., & Ingram, S. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107495 · Cited by 53
Cannabigerol ( CBG ) attenuates mechanical hypersensitivity elicited by chemotherapy‐induced peripheral neuropathy
Sepúlveda, D. E., Morris, D. P., Raup‐Konsavage, W. M., Sun, D., Vrana, K. E., & Graziane, N. (2022) · European Journal of Pain · doi:10.1002/ejp.2016 · Cited by 46
Sex differences in health and disease: A review of biological sex differences relevant to cancer with a spotlight on glioma
Massey, S. C., Whitmire, P., Doyle, T. E., Ippolito, J. E., Mrugała, M. M., Hu, L., Canoll, P., Anderson, A. R. A., Wilson, M. A., Fitzpatrick, S. M., et al. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.07.030 · Cited by 47
The effects of anaesthetics and sedatives on brain inflammation
Dominguini, D., Steckert, A. V., Michels, M., Borges, M. S., Ritter, C., Barichello, T., Thompson, J. P., & Dal‐Pizzol, F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.05.009 · Cited by 44
Sex Differences in Brain Disorders
Ziemka‐Nałęcz, M., Pawelec, P., Ziąbska, K., & Zalewska, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914571 · Cited by 48
Effect of Photobiomodulation in Rescuing Lipopolysaccharide-Induced Dopaminergic Cell Loss in the Male Sprague–Dawley Rat
O'Brien, J. A., & Austin, P. J. (2019) · Biomolecules · doi:10.3390/biom9080381 · Cited by 41
Effects of gut-derived endotoxin on anxiety-like and repetitive behaviors in male and female mice
Fields, C. T., Chassaing, B., Castillo‐Ruiz, A., Osan, R. M., Gewirtz, A. T., & Vries, G. J. D. (2018) · Biology of Sex Differences · doi:10.1186/s13293-018-0166-x · Cited by 41
Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe
Miliano, C., Marti, M., Pintori, N., Castelli, M. P., Tirri, M., Arfè, R., & Luca, M. A. D. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01406 · Cited by 40
Toll-like receptor 3 dynamics in female C57BL/6J mice: Regulation of alcohol intake
Warden, A. S., Azzam, M. M., DaCosta, A., Mason, S., Blednov, Y. A., Messing, R. O., Mayfield, R. D., & Harris, R. A. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.12.006 · Cited by 39
Central metabolism as a potential origin of sex differences in morphine antinociception but not induction of antinociceptive tolerance in mice
Gabel, F., Hovhannisyan, V., Andry, V., & Goumon, Y. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15792 · Cited by 37
Microglia: sculptors of neuropathic pain?
Ward, H. L., & West, S. J. (2020) · Royal Society Open Science · doi:10.1098/rsos.200260 · Cited by 35
Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury
Dukay, B., Walter, F. R., Vigh, J. P., Barabási, B., Hajdu, P., Balassa, T., Migh, E., Kincses, A., Hoyk, Z., Szögi, T., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02070-2 · Cited by 30
Evaluating the Antinociceptive Efficacy of Cannabidiol Alone or in Combination with Morphine Using the Formalin Test in Male and Female Mice
Sepúlveda, D. E., Morris, D. P., Raup‐Konsavage, W. M., Sun, D., Vrana, K. E., & Graziane, N. (2021) · Cannabis and Cannabinoid Research · doi:10.1089/can.2021.0108 · Cited by 31
Acute stress alters recognition memory and AMPA/NMDA receptor subunits in a sex-dependent manner
Torrisi, S. A., Rizzo, S., Laudani, S., Ieraci, A., Drago, F., & Leggio, G. M. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100545 · Cited by 31
Sex differences in effects of gestational polychlorinated biphenyl exposure on hypothalamic neuroimmune and neuromodulator systems in neonatal rats
Bell, M. R., Dryden, A., Will, R. G., & Gore, A. C. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.06.002 · Cited by 30
Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the dorsomedial prefrontal cortex of male and female rats
Liu, S. X., Gades, M. S., Swain, Y., Ramakrishnan, A., Harris, A. C., Tran, P. V., & Gewirtz, J. C. (2021) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2021.108598 · Cited by 31
The Crosstalk between the Blood–Brain Barrier Dysfunction and Neuroinflammation after General Anaesthesia
Yang, X., & Chen, X. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44110386 · Cited by 27
Sex-specific effects of developmental exposure to polychlorinated biphenyls on neuroimmune and dopaminergic endpoints in adolescent rats
Liberman, D. A., Walker, K. A., Gore, A. C., & Bell, M. R. (2020) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2020.106880 · Cited by 26
Sexual dimorphism in immune cell responses following stroke
Liu, J., Satō, Y., Falcone-Juengert, J., Kurisu, K., Shi, J., & Yenari, M. A. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105836 · Cited by 26
Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review
Wang, T., Huang, X., Sun, S., Wang, Y., Han, L., Zhang, T., Zhang, T., & Chen, X. (2025) · Biomedicines · doi:10.3390/biomedicines13010115 · Cited by 27
Assessing the Effects of Parthenolide on Inflammation, Bone Loss, and Glial Cells within a Collagen Antibody-Induced Arthritis Mouse Model
Williams, B., Lees, F., Tsangari, H., Hutchinson, M. R., Perilli, E., & Crotti, T. N. (2020) · Mediators of Inflammation · doi:10.1155/2020/6245798 · Cited by 25
Toll‐like receptor 4 differentially regulates adult hippocampal neurogenesis in an age‐ and sex‐dependent manner
Connolly, M. G., Yost, O. L., Potter, O. V., Giedraitis, M. E., & Kohman, R. A. (2020) · Hippocampus · doi:10.1002/hipo.23209 · Cited by 26
Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss
Parekh, S. V., Paniccia, J. E., Adams, L. O., & Lysle, D. T. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02322-z · Cited by 24
Young and aged TLR4 deficient mice show sex-dependent enhancements in spatial memory and alterations in interleukin-1 related genes
Potter, O. V., Giedraitis, M. E., Johnson, C. D., Cox, M. N., & Kohman, R. A. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.10.010 · Cited by 25
Effects of Toll-like receptor 4 inhibition on spatial memory and cell proliferation in male and female adult and aged mice
Connolly, M. G., Potter, O. V., Sexton, A. R., & Kohman, R. A. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.06.008 · Cited by 23
N ‑Adamantyl Phthalimidine: A New Thalidomide-like Drug That Lacks Cereblon Binding and Mitigates Neuronal and Synaptic Loss, Neuroinflammation, and Behavioral Deficits in Traumatic Brain Injury and LPS Challenge
Hsueh, S., Luo, W., Tweedie, D., Kim, D. S., Kim, Y. K., Hwang, I., Gil, J.-E., Han, B., Chiang, Y. H., Selman, W. R., et al. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.1c00042 · Cited by 22
TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
Feng, Y., Ju, Y.-R., Wu, Q., Sun, G.-Z., & Yan, Z. (2023) · Open Life Sciences · doi:10.1515/biol-2022-0662 · Cited by 18
Sex-based divergence of mechanisms underlying pain and pain inhibition
Mogil, J. S. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.05.005 · Cited by 25
GPR171 Agonist Reduces Chronic Neuropathic and Inflammatory Pain in Male, But Not Female Mice
Ram, A., Edwards, T. M., McCarty, A., Afrose, L., McDermott, M., & Bobeck, E. N. (2021) · Frontiers in Pain Research · doi:10.3389/fpain.2021.695396 · Cited by 19
Toll-like receptors change morphine-induced antinociception, tolerance and dependence: Studies using male and female TLR and signalling gene KO mice
Thomas, J., Lui, L., Abell, A. D., Tieu, W., Somogyi, A. A., Bajic, J. E., & Hutchinson, M. R. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.02.001 · Cited by 20
Endogenous opiates and behavior: 2017
Bodnar, R. J. (2019) · Peptides · doi:10.1016/j.peptides.2019.170223 · Cited by 20
Sex differences in chronic pain-induced mental disorders: Mechanisms of cerebral circuitry
Shen, Z., Li, W., Chang, W., Yue, N., & Yu, J. M. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1102808 · Cited by 22
Microglial alterations induced by psychoactive drugs: A possible mechanism in substance use disorder?
Catale, C., Bussone, S., Iacono, L. L., & Carola, V. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.03.008 · Cited by 20
Sex Differences in Animal Models of Opioid Reward
Lopresti, N. M., Esguerra, M., & Mermelstein, P. G. (2020) · Current Sexual Health Reports · doi:10.1007/s11930-020-00266-4 · Cited by 18
Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus
Bobotis, B. C., Khakpour, M., Braniff, O., de Andrade, E. G., Gargus, M., Allen, M., Carrier, M., Baillargeon, J., Rangachari, M., & Tremblay, M.-È. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03341-6 · Cited by 17
Fundamental sex differences in morphine withdrawal-induced neuronal plasticity
Hadschieff, V., Drdla-Schutting, R., Springer, D. N., Siegert, A., Schroeder, H., & Sandkühler, J. (2020) · Pain · doi:10.1097/j.pain.0000000000001901 · Cited by 18
Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice
Reiss, D. J., Maurin, H., Audouard, E., Martínez‐Navarro, M., Xue, Y., Hérault, Y., Maldonado, R. J., Cabañero, D., & Gavériaux‐Ruff, C. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.745178 · Cited by 21
Central amygdala inflammation drives pain hypersensitivity and attenuates morphine analgesia in experimental autoimmune encephalomyelitis
Dworsky-Fried, Z., Faig, C. A., Vogel, H. A., Kerr, B. J., & Taylor, A. M. W. (2021) · Pain · doi:10.1097/j.pain.0000000000002307 · Cited by 18
Sex differences in neuro(auto)immunity and chronic sciatic nerve pain
Linher‐Melville, K., Shah, A. A., & Singh, G. (2020) · Biology of Sex Differences · doi:10.1186/s13293-020-00339-y · Cited by 17
Anterior cingulate cortex and its projections to the ventral tegmental area regulate opioid withdrawal, the formation of opioid context associations and context-induced drug seeking
McKendrick, G., McDevitt, D. S., Shafeek, P., Cottrill, A. R., & Graziane, N. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.972658 · Cited by 17
Perinatal Opioid Exposure Leads to Decreased Social Play in Adolescent Male and Female Rats: Potential Role of Oxytocin Signaling in Brain Regions Associated with Social Reward
Harder, H. J., Searles, C. T., Vogt, M. E., & Murphy, A. Z. (2023) · Hormones and Behavior · doi:10.1016/j.yhbeh.2023.105384 · Cited by 16
Self-citation
The importance of translationally evaluating steroid hormone contributions to substance use
Maher, E. E., Strzelecki, A. M., Weafer, J. J., & Gipson, C. D. (2023) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2023.101059 · Cited by 16
A novel role for astrocytic fragmented mitochondria in regulating morphine addiction
Rao, J., Sun, W., Wang, X., Li, J., Zhang, Z., & Zhou, F. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.07.030 · Cited by 15
Paclitaxel-Associated Mechanical Sensitivity and Neuroinflammation Are Sex-, Time-, and Site-Specific and Prevented through Cannabigerol Administration in C57Bl/6 Mice
Li, H., & Ward, S. J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084277 · Cited by 15
Nuclear factor kappa B signaling within the rat nucleus accumbens core sex-dependently regulates cue-induced cocaine seeking and matrix metalloproteinase-9 expression
Namba, M. D., Phillips, M. N., Neisewander, J. L., & Olive, M. F. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.03.002 · Cited by 14
Sex differences in the amygdaloid projections to the ventrolateral periaqueductal gray and their activation during inflammatory pain in the rat
Cantu, D. J., Kaur, S., Murphy, A. Z., & Averitt, D. L. (2022) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2022.102123 · Cited by 16
Self-citation
Pain mechanisms in the transgender individual: a review
Anger, J. T., Case, L. K., Baranowski, A. P., Berger, A. S., Craft, R. M., Damitz, L., Gabriel, R. A., Harrison, T. E., Kaptein, K., Lee, S., et al. (2024) · Frontiers in Pain Research · doi:10.3389/fpain.2024.1241015 · Cited by 15
Self-citation

Authors: Doyle, H. H., Eidson, L. N., Sinkiewicz, D. M., & Murphy, A. Z.
Affiliations: Georgia State University (US)
ORCID: Doyle, Hillary H.
Murphy, Anne Z.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2017-02-20
Volume: 37
Issue: 12
Pages: 3202-3214
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.2906-16.2017
PMC: PMC5373114
OpenAlex: W2589516850
Cited by: 166
References: 96
Citations by year: 2026: 5 · 2025: 16 · 2024: 12 · 2023: 14 · 2022: 19 · 2021: 37 · 2020: 23 · 2019: 16 · 2018: 17 · 2017: 6
FWCI: 12.55
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 214 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute on Drug Abuse (R01DA016272)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: sex differences, microglial activation, periaqueductal gray, morphine, TLR4, neuroinflammation, lipopolysaccharide, IL-1β, naloxone, opioid analgesia, pain management
MeSH terms: Animals, Cell Count, Dose-Response Relationship, Drug, Drug Resistance, Female, Male, Morphine, Periaqueductal Gray, Sex Characteristics, Rats, Sprague-Dawley, Microglia, Toll-Like Receptor 4, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Sex Differences in Microglia Activity within the Periaqueductal Gray of the Rat: A Potential Mechanism Driving the Dimorphic Effects of Morphine

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks