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Differential regulation of pruritic sensation and emotion by cannabinoid type 1 receptors on mPFC glutamatergic and GABAergic neurons

Acta Pharmacologica Sinica volume 46, pages 904–921 (2025)Cite this article

Abstract

Itch causes a strong urge to scratch and induces negative emotions, such as aversion and anxiety. Antihistamine medications are key in the clinical management of pruritus, but their therapeutic efficacy in controlling moderate and severe itching remains limited. The neural circuits in the brain that process itching and itch-induced aversion and anxiety remain unclear so far. Human brain imaging suggests that the medial prefrontal cortex (mPFC) is involved in processing the emotional and motivational components of itching. In this study, we investigated the mechanisms by which glutamatergic and GABAergic neurons in mPFC differentially regulated pruritic sensation and emotion through cannabinoid type 1 receptors (CB1Rs). Chloroquinoline (CQ)-induced acute and calcipotriol (MC903)-induced chronic itch models were established. Fiberoptic calcium imaging was used to detect the activity of the two types of neurons in response to itching. The CB1R antagonist AM251 (0.5 mg in 200 nL) was microinjected into the mPFC through the implanted cannula. We showed that chemogenetic activation of glutamatergic neurons and inhibition of GABAergic neurons in the mPFC reduced scratching and chronic itch-induced anxiety. GABAergic, but not glutamatergic, neurons were involved in acute itch-induced aversion. CB1Rs on glutamatergic and GABAergic neurons modulated chronic itch-induced scratching and anxiety in divergent manners. However, CB1Rs did not affect acute itch-induced scratching. CB1Rs on GABAergic, but not glutamatergic, neurons regulated acute itch-induced aversion. These results may guide the development of therapeutic strategies targeting CB1Rs to treat itch-induced sensory and emotional responses.

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Fig. 1: Bilateral lesions of the mPFC attenuated itch-induced scratching and affective behaviors.
Fig. 2: Ca2+ dynamics of glutamatergic and GABAergic neurons in the mPFC in response to itch.
Fig. 3: Glutamatergic neurons in the mPFC modulated itch-induced scratching behavior.
Fig. 4: Glutamatergic neurons in the mPFC modulated itch-induced aversion and anxiety.
Fig. 5: Chemogenic modulation of GABAergic neuronal activity in the mPFC altered itch-induced scratching behaviors.
Fig. 6: Chemogenic modulation of GABAergic neuronal activity in the mPFC altered itch-induced aversion and anxiety.
Fig. 7: Itch-induced changes on EEG.
Fig. 8: Inhibition of CB1Rs in the mPFC modulated itch and itch-induced aversion and anxiety.
Fig. 9: CB1Rs on glutamatergic neurons modulated itch- and itch-induced aversion and anxiety.
Fig. 10: CB1Rs on GABAergic neurons modulated itch and itch-induced aversion and anxiety.

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References

  1. Schonmann Y, Mansfield KE, Hayes JF, Abuabara K, Roberts A, Smeeth L, et al. Atopic eczema in adulthood and risk of depression and anxiety: a population-based cohort study. J Allergy Clin Immunol Pract. 2020;8:248–57.e16.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Patel KR, Immaneni S, Singam V, Rastogi S, Silverberg JI. Association between atopic dermatitis, depression, and suicidal ideation: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:402–10.

    Article  PubMed  Google Scholar 

  3. Umehara Y, Kiatsurayanon C, Trujillo-Paez JV, Chieosilapatham P, Peng G, Yue H, et al. Intractable itch in atopic dermatitis: causes and treatments. Biomedicines. 2021;9:229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Moosa AS, Leng NSY, Kum CL, Tan NC. A qualitative research study on the illness perception of chronic pruritus in older asian adults based on the common-sense model of self-regulation. Health Expect. 2021;24:1801–11.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Angley M, Drews-Botsch C, Lewis TT, Badell M, Lim SS, Howards PP. Adverse perinatal outcomes before and after diagnosis of systemic lupus erythematosus among African American women. Arthritis Care Res. 2022;74:904–11.

    Article  Google Scholar 

  6. Dong X, Dong X. Peripheral and central mechanisms of itch. Neuron. 2018;98:482–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zeng F, Zeng F, Sugiyama N, Nogami M, Murakami T. A case of rectal dissemination of gastric cancer diagnosed by simultaneous 18F-FDG PET/MRI. Clin Nucl Med. 2023;48:e441–e3.

    Article  PubMed  Google Scholar 

  8. Zheng J, Zhang XM, Tang W, Li Y, Wang P, Jin J, et al. An insular cortical circuit required for itch sensation and aversion. Curr Biol. 2024;34:1453–68.e6.

    Article  CAS  PubMed  Google Scholar 

  9. Samineni VK, Grajales-Reyes JG, Grajales-Reyes GE, Tycksen E, Copits BA, Pedersen C, et al. Cellular, circuit and transcriptional framework for modulation of itch in the central amygdala. Elife. 2021;10:e68130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Su XY, Chen M, Yuan Y, Li Y, Guo SS, Luo HQ, et al. Central processing of itch in the midbrain reward center. Neuron. 2019;102:858–72.e5.

    Article  CAS  PubMed  Google Scholar 

  11. Chen T, Zhu SJ, Xu S, Wang YQ, Aji A, Zhang C, et al. Resting-state fMRI reveals changes within the anxiety and social avoidance circuitry of the brain in mice with psoriasis-like skin lesions. Exp Dermatol. 2023;32:1900–14.

    Article  CAS  PubMed  Google Scholar 

  12. Papoiu ADP, Kraft RA, Coghill RC, Yosipovitch G. Butorphanol suppression of histamine itch is mediated by nucleus accumbens and septal nuclei: a pharmacological fMRI study. J Invest Dermatol. 2015;135:560–8.

    Article  CAS  PubMed  Google Scholar 

  13. Pan Q, Guo SS, Chen M, Su XY, Gao ZL, Wang Q, et al. Representation and control of pain and itch by distinct prefrontal neural ensembles. Neuron. 2023;111:2414–31.e7.

    Article  CAS  PubMed  Google Scholar 

  14. Chen M, He T, Yi XH, Tang MC, Long JH, Wang PJ, et al. Infralimbic cortex-medial striatum projections modulate the itch processing. Exp Neurol. 2022;354:114101.

    Article  PubMed  Google Scholar 

  15. Zhang TT, Guo SS, Wang HY, Jing Q, Yi X, Hu ZH, et al. An anterior cingulate cortex-to-midbrain projection controls chronic itch in mice. Neurosci Bull. 2023;39:793–807.

    Article  PubMed  Google Scholar 

  16. Ziegler DR, Cullinan WE, Herman JP. Distribution of vesicular glutamate transporter mRNA in rat hypothalamus. J Comp Neurol. 2002;448:217–29.

    Article  CAS  PubMed  Google Scholar 

  17. Bai L, Xu H, Collins JF, Ghishan FK. Molecular and functional analysis of a novel neuronal vesicular glutamate transporter. J Biol Chem. 2001;276:36764–9.

    Article  CAS  PubMed  Google Scholar 

  18. Vrettou M, Granholm L, Todkar A, Nilsson KW, Wallen-Mackenzie A, Nylander I, et al. Ethanol affects limbic and striatal presynaptic glutamatergic and DNA methylation gene expression in outbred rats exposed to early-life stress. Addict Biol. 2017;22:369–80.

    Article  CAS  PubMed  Google Scholar 

  19. Vrettou M, Yan L, Nilsson KW, Wallen-Mackenzie A, Nylander I, Comasco E. DNA methylation of vesicular glutamate transporters in the mesocorticolimbic brain following early-life stress and adult ethanol exposure-an explorative study. Sci Rep. 2021;11:15322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mao X, Staiger JF. Multimodal cortical neuronal cell type classification. Pflug Arch. 2024;476:721–33.

    Article  CAS  Google Scholar 

  21. Huang ZJ. Toward a genetic dissection of cortical circuits in the mouse. Neuron. 2014;83:1284–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Harris KD, Shepherd GM. The neocortical circuit: themes and variations. Nat Neurosci. 2015;18:170–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xu P, Chen A, Li Y, Xing X, Lu H. Medial prefrontal cortex in neurological diseases. Physiol Genomics. 2019;51:432–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li JN, Wu XM, Zhao LJ, Sun HX, Hong J, Wu FL, et al. Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice. Nat Commun. 2023;14:2539.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gaffal E, Cron M, Glodde N, Bald T, Kuner R, Zimmer A, et al. Cannabinoid 1 receptors in keratinocytes modulate proinflammatory chemokine secretion and attenuate contact allergic inflammation. J Immunol. 2013;190:4929–36.

    Article  CAS  PubMed  Google Scholar 

  26. Liu X, Li L, Jiang J, Ge W, Huang Y, Jin Z, et al. Role of type I cannabinoid receptor in sensory neurons in psoriasiform skin inflammation and pruritus. J Invest Dermatol. 2023;143:812–21.e3.

    Article  CAS  PubMed  Google Scholar 

  27. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 2007;370:1706–13.

    Article  CAS  PubMed  Google Scholar 

  28. Bilir KA, Anli G, Ozkan E, Gunduz O, Ulugol A. Involvement of spinal cannabinoid receptors in the antipruritic effects of win 55,212-2, a cannabinoid receptor agonist. Clin Exp Dermatol. 2018;43:553–8.

    Article  CAS  PubMed  Google Scholar 

  29. Lisboa SF, Borges AA, Nejo P, Fassini A, Guimaraes FS, Resstel LB. Cannabinoid Cb1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: additional evidence. Prog Neuropsychopharmacol Biol Psychiatry. 2015;59:76–83.

    Article  CAS  PubMed  Google Scholar 

  30. Imperatore R, Morello G, Luongo L, Taschler U, Romano R, De Gregorio D, et al. Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid receptor Cb(1)R signaling and anxiety-like behavior. J Neurochem. 2015;135:799–813.

    Article  CAS  PubMed  Google Scholar 

  31. Nagy-Pal P, Veres JM, Fekete Z, Karlocai MR, Weisz F, Barabas B, et al. Structural organization of perisomatic inhibition in the mouse medial prefrontal cortex. J Neurosci. 2023;43:6972–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yeom M, Ahn S, Jang SY, Jang JH, Lee Y, Hahm DH, et al. Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice. Biol Res. 2022;55:28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. He ZX, Xi K, Liu KJ, Yue MH, Wang Y, Yin YY, et al. A nucleus accumbens Tac1 neural circuit regulates avoidance responses to aversive stimuli. Int J Mol Sci. 2023;24:4346.

  34. Yin JB, Liang SH, Li F, Zhao WJ, Bai Y, Sun Y, et al. dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors. J Clin Invest. 2020;130:6555–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mu D, Sun YG. Itch induces conditioned place aversion in mice. Neurosci Lett. 2017;658:91–6.

    Article  CAS  PubMed  Google Scholar 

  36. Samineni VK, Grajales-Reyes JG, Sundaram SS, Yoo JJ, Gereau RWT. Cell type-specific modulation of sensory and affective components of itch in the periaqueductal gray. Nat Commun. 2019;10:4356.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Kvitsiani D, Ranade S, Hangya B, Taniguchi H, Huang JZ, Kepecs A. Distinct behavioural and network correlates of two interneuron types in prefrontal cortex. Nature. 2013;498:363–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Takahashi S, Ochiai S, Jin J, Takahashi N, Toshima S, Ishigame H, et al. Sensory neuronal Stat3 is critical for IL-31 receptor expression and inflammatory itch. Cell Rep. 2023;42:113433.

    Article  CAS  PubMed  Google Scholar 

  39. Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev. 2003;83:1017–66.

    Article  CAS  PubMed  Google Scholar 

  40. Asano T, Takemoto H, Horita T, Tokutake T, Izuo N, Mochizuki T, et al. Sleep disturbance after cessation of cannabis administration in mice. Neuropsychopharmacol Rep. 2023;43:505–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Xie JF, Wang LX, Ren WT, Wang C, Gao JX, Chen HL, et al. An alpha-hemoglobin-derived peptide (m)Vd-hemopressin (Alpha) promotes NREM sleep via the Cb1 cannabinoid receptor. Front Pharmacol. 2023;14:1213215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang Z, Gadotti VM, Chen L, Souza IA, Stemkowski PL, Zamponi GW. Role of prelimbic GABAergic circuits in sensory and emotional aspects of neuropathic pain. Cell Rep. 2015;12:752–9.

    Article  CAS  PubMed  Google Scholar 

  43. Pastor V, Medina JH. Medial prefrontal cortical control of reward- and aversion-based behavioral output: bottom-up modulation. Eur J Neurosci. 2021;53:3039–62.

    Article  CAS  PubMed  Google Scholar 

  44. Kuner R, Kuner T. Cellular circuits in the brain and their modulation in acute and chronic pain. Physiol Rev. 2021;101:213–58.

    Article  CAS  PubMed  Google Scholar 

  45. Sun Q, Li X, Ren M, Zhao M, Zhong Q, Ren Y, et al. A whole-brain map of long-range inputs to gabaergic interneurons in the mouse medial prefrontal cortex. Nat Neurosci. 2019;22:1357–70.

    Article  CAS  PubMed  Google Scholar 

  46. Malik R, Li Y, Schamiloglu S, Sohal VS. Top-down control of hippocampal signal-to-noise by prefrontal long-range inhibition. Cell. 2022;185:1602–17.e17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Dinh HT, Nishimaru H, Le QV, Matsumoto J, Setogawa T, Maior RS, et al. Preferential neuronal responses to snakes in the monkey medial prefrontal cortex support an evolutionary origin for ophidiophobia. Front Behav Neurosci. 2021;15:653250.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Fu S, Sun H, Wang J, Gao S, Zhu L, Cui K, et al. Impaired neuronal macroautophagy in the prelimbic cortex contributes to comorbid anxiety-like behaviors in rats with chronic neuropathic pain. Autophagy. 2024;20:1559–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Song H, Lu X, Du D, Peng Y, Pan W, Xu X, et al. Gegen-qinlian decoction-A traditional Chinese medicine formula-alleviates methamphetamine withdrawal induced anxiety by targeting gabaergic interneuron-pyramidal neuron pathway in mPFC. Addict Biol. 2023;28:e13314.

    Article  CAS  PubMed  Google Scholar 

  50. Zhou Q, Jiang N, Dong Y, Tian K. Dexmedetomidine alleviates anxiety-like behaviors in female mice with musculoskeletal pain through Sirt1/p53 axis. Brain Res Bull. 2023;201:110698.

    Article  CAS  PubMed  Google Scholar 

  51. Xue B, Ma YY, Zhu JY, Mu Y, Li YH, Shen F, et al. Chronic social comparison elicits depression- and anxiety-like behaviors and alterations in brain-derived neurotrophic factor expression in male rats. Anim Cogn. 2023;26:1505–19.

    Article  PubMed  Google Scholar 

  52. Tremblay R, Lee S, Rudy B. GABAergic interneurons in the neocortex: from cellular properties to circuits. Neuron. 2016;91:260–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Miyoshi G. Elucidating the developmental trajectories of gabaergic cortical interneuron subtypes. Neurosci Res. 2019;138:26–32.

    Article  CAS  PubMed  Google Scholar 

  54. Tong X, Wu J, Sun R, Li H, Hong Y, Liu X, et al. Elevated dorsal medial prefrontal cortex to lateral habenula pathway activity mediates chronic stress-induced depressive and anxiety-like behaviors. Neuropsychopharmacology. 2024;49:1402–11.

    Article  PubMed  Google Scholar 

  55. Granja-Galeano G, Dominguez-Rubio AP, Zappia CD, Wolfson M, Sanz-Blasco S, Aisemberg J, et al. CB1 receptor expression and signaling are required for dexamethasone-induced aversive memory consolidation. Neuropharmacology. 2023;239:109674.

    Article  CAS  PubMed  Google Scholar 

  56. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev. 2009;89:309–80.

    Article  CAS  PubMed  Google Scholar 

  57. Wu J, Hua L, Liu W, Yang X, Tang X, Yuan S, et al. Electroacupuncture exerts analgesic effects by restoring hyperactivity via cannabinoid type 1 receptors in the anterior cingulate cortex in chronic inflammatory pain. Mol Neurobiol. 2024;61:2949–63.

    Article  CAS  PubMed  Google Scholar 

  58. Marinelli S, Pacioni S, Cannich A, Marsicano G, Bacci A. Self-modulation of neocortical pyramidal neurons by endocannabinoids. Nat Neurosci. 2009;12:1488–90.

    Article  CAS  PubMed  Google Scholar 

  59. Cong J, Lu K, Zou W, Li Z, Guo Z, Tong X, et al. Astroglial CB1 cannabinoid receptors mediate CP 55,940-induced conditioned place aversion through cyclooxygenase-2 signaling in mice. Front Cell Neurosci. 2021;15:772549.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Humburg BA, Jordan CJ, Zhang HY, Shen H, Han X, Bi GH, et al. Optogenetic brain-stimulation reward: a new procedure to re-evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter-Cre mice. Addict Biol. 2021;26:e13005.

    Article  CAS  PubMed  Google Scholar 

  61. Borges-Assis AB, Uliana DL, Hott SC, Guimaraes FS, Lisboa SF, Resstel LBM. Bed nucleus of the stria terminalis CB1 receptors and the FAAH enzyme modulate anxiety behavior depending on previous stress exposure. Prog Neuropsychopharmacol Biol Psychiatry. 2023;125:110739.

    Article  CAS  PubMed  Google Scholar 

  62. Gonczarowska N, Tomaz C, Caixeta FV, Malcher-Lopes R, Barros M, Nishijo H, et al. CB1 receptor antagonism in Capuchin monkeys alters social interaction and aversive memory extinction. Psychopharmacology. 2019;236:3413–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr. He Zhu (Zhanjiang Central People’s Hospital) for kindly providing adult Vglut2-Cre and Vgat-Cre mice. This work was supported by grants from the National Youth Natural Science Foundation (82205275, 82305002) and the Chinese Postdoctoral Foundation (0106510145, 0106510062).

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  1. These authors contributed equally: Ou-Yang Zhanmu, Yang Yang.

Authors and Affiliations

  1. School of Basic Medical Science, Tongji Medical College; Key Laboratory of Neurological Diseases of Hubei Province and National Education Ministry, Huazhong University of Science and Technology, Wuhan, China

    Ou-Yang Zhanmu, Yang Yang, Bin Feng, Hong-yang Wang, Hao Li, Hui-juan Zhou, Wen-qiang Ge, Ke-xing Wan, Sui-xi Wang, Kai-ling Zhang, Hong Zhang, Lei Pei, Qing Tian & Man Li

  2. Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Hui-lin Pan

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Contributions

ML and QT designed all the experiments and revised the manuscript. OYZM performed the virus injection, behavioral tests, and western blotting; analyzed the data; and drafted the manuscript. YY performed virus injection, analyzed the data, and revised the manuscript. BF performed the EEG. HYW assisted with the fiber photometry and performed the electrophysiology experiments. HL provided assistance with cannula implantation and optogenetic modulation. HJZ performed the western blotting. HLP edited the manuscript. WQG, KXW, LP, KLZ, SXW and HZ helped to revise the article. All the experiments were supervised by ML and QT. All authors approved the final version of the manuscript.

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Correspondence to Qing Tian or Man Li.

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Zhanmu, OY., Yang, Y., Feng, B. et al. Differential regulation of pruritic sensation and emotion by cannabinoid type 1 receptors on mPFC glutamatergic and GABAergic neurons. Acta Pharmacol Sin 46, 904–921 (2025). https://doi.org/10.1038/s41401-024-01426-1

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