Effect of purinergic receptors in neuropathic pain_West China Medical Journal

Authors：

CHEN Mingkai , OU Mengchan ,  LI Yu

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

LI Yu, Email: liyu1963@163.com

Keywords：

Neuropathic pain; Astrocyte; Microglia; Purinergic signaling

DOI：

10.7507/1002-0179.202002026

Video：

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Neuropathic pain has been redefined by NeuPSIG as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory syste”. However, pharmacological management for neuropathic pain is not effective, which is correlated with the uncertainty of pathogenesis. For a long time, neuron had been considered acting a major role in the development of neuropathic pain. In recent years, a majority of studies revealed that glia cell also involved in the occurrence and development of neuropathic pain, and neuron-glia interaction is one of the key mechanism of neuropathic pain, including complex signaling pathways as purinergic signaling. This review focuses on recent advances on the role of purinergic receptors in neuropathic pain.

Citation： CHEN Mingkai, OU Mengchan, LI Yu. Effect of purinergic receptors in neuropathic pain. West China Medical Journal, 2021, 36(11): 1618-1622. doi: 10.7507/1002-0179.202002026 Copy

1.	Haanpää M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain, 2011, 152(1): 14-27.
2.	Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol, 2010, 9(8): 807-819.
3.	Deumens R, Jaken RJ, Knaepen L, et al. Inverse relation between intensity of GFAP expression in the substantia gelatinosa and degree of chronic mechanical allodynia. Neurosci Lett, 2009, 452(2): 101-105.
4.	Del Puerto A, Wandosell F, Garrido JJ. Neuronal and glial purinergic receptors functions in neuron development and brain disease. Front Cell Neurosci, 2013, 7: 197.
5.	Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci, 2016, 18(1): 20-30.
6.	Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. Pain, 2018, 159(3): 595-602.
7.	Block L. Glial dysfunction and persistent neuropathic postsurgical pain. Scand J Pain, 2016, 10: 74-81.
8.	Chiang CY, Sessle BJ, Dostrovsky JO. Role of astrocytes in pain. Neurochem Res, 2012, 37(11): 2419-2431.
9.	Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy?. Pain, 2013, 154 (Suppl 1): S10-S28.
10.	von Kügelgen I. Pharmacology of P2Y receptors. Brain Res Bull, 2019, 151: 12-24.
11.	Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev, 2007, 87(2): 659-797.
12.	Burnstock G. P2X ion channel receptors and inflammation. Purinergic Signal, 2016, 12(1): 59-67.
13.	Kobayashi K, Yamanaka H, Noguchi K. Expression of ATP receptors in the rat dorsal root ganglion and spinal cord. Anat Sci Int, 2013, 88(1): 10-16.
14.	Jacobson KA, Müller CE. Medicinal chemistry of adenosine, P2Y and P2X receptors. Neuropharmacology, 2016, 104: 31-49.
15.	Dalgarno R, Leduc-Pessah H, Pilapil A, et al. Intrathecal delivery of a palmitoylated peptide targeting Y382-384 within the P2X7 receptor alleviates neuropathic pain. Mol Pain, 2018, 14: 1744806918795793.
16.	He Y, Taylor N, Fourgeaud L, et al. The role of microglial P2X7: modulation of cell death and cytokine release. J Neuroinflammation, 2017, 14(1): 135.
17.	Inoue K. Role of the P2X4 receptor in neuropathic pain. Curr Opin Pharmacol, 2019, 47: 33-39.
18.	Barragán-Iglesias P, Pineda-Farias JB, Bravo-Hernández M, et al. Predominant role of spinal P2Y1 receptors in the development of neuropathic pain in rats. Brain Res, 2016, 1636: 43-51.
19.	Shigetomi E, Hirayama YJ, Ikenaka K, et al. Role of purinergic receptor P2Y1 in spatiotemporal Ca²⁺ dynamics in astrocytes. J Neurosci, 2018, 38(6): 1383-1395.
20.	Magni G, Ceruti S. The role of adenosine and P2Y receptors expressed by multiple cell types in pain transmission. Brain Res Bull, 2019, 151: 132-143.
21.	Li N, Lu ZY, Yu LH, et al. Inhibition of G protein-coupled P2Y2 receptor induced analgesia in a rat model of trigeminal neuropathic pain. Mol Pain, 2014, 10: 21.
22.	Shi Y, Qin W, Nie F, et al. Ulinastatin attenuates neuropathic pain via the ATP/P2Y2 receptor pathway in rat models. Gene, 2017, 627: 263-270.
23.	Vit JP, Jasmin L, Bhargava A, et al. Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain. Neuron Glia Biol, 2006, 2(4): 247-257.
24.	Weick M, Cherkas PS, Härtig W, et al. P2 receptors in satellite glial cells in trigeminal ganglia of mice. Neuroscience, 2003, 120(4): 969-977.
25.	Strøbaek D, Teuber L, Jørgensen TD, et al. Activation of human IK and SK Ca²⁺ -activated K⁺ channels by NS309 (6, 7-dichloro-1H-indole-2, 3-dione 3-oxime). Biochim Biophys Acta, 2004, 1665(1/2): 1-5.
26.	Huang D, Yang J, Liu X, et al. P2Y₆ receptor activation is involved in the development of neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. J Clin Neurosci, 2018, 56: 156-162.
27.	Wang Z, Zhao W, Shen X, et al. The role of P2Y6 receptors in the maintenance of neuropathic pain and its improvement of oxidative stress in rats. J Cell Biochem, 2019, 120(10): 17123-17130.
28.	Barragán-Iglesias P, Pineda-Farias JB, Cervantes-Durán C, et al. Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells. Mol Pain, 2014, 10: 29.
29.	Gu N, Eyo UB, Murugan M, et al. Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain. Brain Behav Immun, 2016, 55: 82-92.
30.	Horváth G, Gölöncsér F, Csölle C, et al. Central P2Y12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents. Neurobiol Dis, 2014, 70: 162-178.
31.	Sugawara S, Okada S, Katagiri A, et al. Interaction between calcitonin gene-related peptide-immunoreactive neurons and satellite cells via P2Y₁₂ R in the trigeminal ganglion is involved in neuropathic tongue pain in rats. Eur J Oral Sci, 2017, 125(6): 444-452.
32.	Zhou R, Xu T, Liu X, et al. Activation of spinal dorsal horn P2Y₁₃ receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain. J Pain Res, 2018, 11: 615-628.
33.	Tatsumi E, Yamanaka H, Kobayashi K, et al. RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain. Glia, 2015, 63(2): 216-228.
34.	Kobayashi K, Yamanaka H, Yanamoto F, et al. Multiple P2Y subtypes in spinal microglia are involved in neuropathic pain after peripheral nerve injury. Glia, 2012, 60(10): 1529-1539.
35.	Lin J, Liu F, Zhang YY, et al. P2Y₁₄ receptor is functionally expressed in satellite glial cells and mediates interleukin-1β and chemokine CCL2 secretion. J Cell Physiol, 2019, 234(11): 21199-21210.
36.	Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers, 2017, 3: 17002.
37.	Wright ME, Rizzolo D. An update on the pharmacologic management and treatment of neuropathic pain. JAAPA, 2017, 30(3): 13-17.

1. Haanpää M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment. Pain, 2011, 152(1): 14-27.
2. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol, 2010, 9(8): 807-819.
3. Deumens R, Jaken RJ, Knaepen L, et al. Inverse relation between intensity of GFAP expression in the substantia gelatinosa and degree of chronic mechanical allodynia. Neurosci Lett, 2009, 452(2): 101-105.
4. Del Puerto A, Wandosell F, Garrido JJ. Neuronal and glial purinergic receptors functions in neuron development and brain disease. Front Cell Neurosci, 2013, 7: 197.
5. Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci, 2016, 18(1): 20-30.
6. Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. Pain, 2018, 159(3): 595-602.
7. Block L. Glial dysfunction and persistent neuropathic postsurgical pain. Scand J Pain, 2016, 10: 74-81.
8. Chiang CY, Sessle BJ, Dostrovsky JO. Role of astrocytes in pain. Neurochem Res, 2012, 37(11): 2419-2431.
9. Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy?. Pain, 2013, 154 (Suppl 1): S10-S28.
10. von Kügelgen I. Pharmacology of P2Y receptors. Brain Res Bull, 2019, 151: 12-24.
11. Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev, 2007, 87(2): 659-797.
12. Burnstock G. P2X ion channel receptors and inflammation. Purinergic Signal, 2016, 12(1): 59-67.
13. Kobayashi K, Yamanaka H, Noguchi K. Expression of ATP receptors in the rat dorsal root ganglion and spinal cord. Anat Sci Int, 2013, 88(1): 10-16.
14. Jacobson KA, Müller CE. Medicinal chemistry of adenosine, P2Y and P2X receptors. Neuropharmacology, 2016, 104: 31-49.
15. Dalgarno R, Leduc-Pessah H, Pilapil A, et al. Intrathecal delivery of a palmitoylated peptide targeting Y382-384 within the P2X7 receptor alleviates neuropathic pain. Mol Pain, 2018, 14: 1744806918795793.
16. He Y, Taylor N, Fourgeaud L, et al. The role of microglial P2X7: modulation of cell death and cytokine release. J Neuroinflammation, 2017, 14(1): 135.
17. Inoue K. Role of the P2X4 receptor in neuropathic pain. Curr Opin Pharmacol, 2019, 47: 33-39.
18. Barragán-Iglesias P, Pineda-Farias JB, Bravo-Hernández M, et al. Predominant role of spinal P2Y1 receptors in the development of neuropathic pain in rats. Brain Res, 2016, 1636: 43-51.
19. Shigetomi E, Hirayama YJ, Ikenaka K, et al. Role of purinergic receptor P2Y1 in spatiotemporal Ca²⁺ dynamics in astrocytes. J Neurosci, 2018, 38(6): 1383-1395.
20. Magni G, Ceruti S. The role of adenosine and P2Y receptors expressed by multiple cell types in pain transmission. Brain Res Bull, 2019, 151: 132-143.
21. Li N, Lu ZY, Yu LH, et al. Inhibition of G protein-coupled P2Y2 receptor induced analgesia in a rat model of trigeminal neuropathic pain. Mol Pain, 2014, 10: 21.
22. Shi Y, Qin W, Nie F, et al. Ulinastatin attenuates neuropathic pain via the ATP/P2Y2 receptor pathway in rat models. Gene, 2017, 627: 263-270.
23. Vit JP, Jasmin L, Bhargava A, et al. Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain. Neuron Glia Biol, 2006, 2(4): 247-257.
24. Weick M, Cherkas PS, Härtig W, et al. P2 receptors in satellite glial cells in trigeminal ganglia of mice. Neuroscience, 2003, 120(4): 969-977.
25. Strøbaek D, Teuber L, Jørgensen TD, et al. Activation of human IK and SK Ca²⁺ -activated K⁺ channels by NS309 (6, 7-dichloro-1H-indole-2, 3-dione 3-oxime). Biochim Biophys Acta, 2004, 1665(1/2): 1-5.
26. Huang D, Yang J, Liu X, et al. P2Y₆ receptor activation is involved in the development of neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. J Clin Neurosci, 2018, 56: 156-162.
27. Wang Z, Zhao W, Shen X, et al. The role of P2Y6 receptors in the maintenance of neuropathic pain and its improvement of oxidative stress in rats. J Cell Biochem, 2019, 120(10): 17123-17130.
28. Barragán-Iglesias P, Pineda-Farias JB, Cervantes-Durán C, et al. Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells. Mol Pain, 2014, 10: 29.
29. Gu N, Eyo UB, Murugan M, et al. Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain. Brain Behav Immun, 2016, 55: 82-92.
30. Horváth G, Gölöncsér F, Csölle C, et al. Central P2Y12 receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents. Neurobiol Dis, 2014, 70: 162-178.
31. Sugawara S, Okada S, Katagiri A, et al. Interaction between calcitonin gene-related peptide-immunoreactive neurons and satellite cells via P2Y₁₂ R in the trigeminal ganglion is involved in neuropathic tongue pain in rats. Eur J Oral Sci, 2017, 125(6): 444-452.
32. Zhou R, Xu T, Liu X, et al. Activation of spinal dorsal horn P2Y₁₃ receptors can promote the expression of IL-1β and IL-6 in rats with diabetic neuropathic pain. J Pain Res, 2018, 11: 615-628.
33. Tatsumi E, Yamanaka H, Kobayashi K, et al. RhoA/ROCK pathway mediates p38 MAPK activation and morphological changes downstream of P2Y12/13 receptors in spinal microglia in neuropathic pain. Glia, 2015, 63(2): 216-228.
34. Kobayashi K, Yamanaka H, Yanamoto F, et al. Multiple P2Y subtypes in spinal microglia are involved in neuropathic pain after peripheral nerve injury. Glia, 2012, 60(10): 1529-1539.
35. Lin J, Liu F, Zhang YY, et al. P2Y₁₄ receptor is functionally expressed in satellite glial cells and mediates interleukin-1β and chemokine CCL2 secretion. J Cell Physiol, 2019, 234(11): 21199-21210.
36. Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain. Nat Rev Dis Primers, 2017, 3: 17002.
37. Wright ME, Rizzolo D. An update on the pharmacologic management and treatment of neuropathic pain. JAAPA, 2017, 30(3): 13-17.

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