{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:42:54Z","timestamp":1792226574874,"version":"4.4.0"},"reference-count":63,"publisher":"Baycinar Tibbi Yayincilik","issue":"4","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Agri"],"accepted":{"date-parts":[[2026,7,10]]},"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    This study aims to investigate the muscarinic receptor-associated Z944 responses on hyperalgesia resulting from chronic constriction injury (CCI) of the rat sciatic nerve.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Materials and Methods:<\/jats:bold>\n                    A total of 72 male Wistar Albino rats (200-250 g) were randomly divided into eight groups. The right sciatic nerve CCI of Wistar Albino rats was performed except the Saline intraperitoneal (i.p.) group. Two weeks after the operations, pressure test of both paws and hot plate test were performed in the groups of Saline, CCI + Saline, CCI + DMSO (i.p.), CCI + 1 mg\/kg Atropine (i.p), CCI + Z944 1, 3, 10 mg\/kg (i.p) dose and CCI + 1 mg\/kg Atropine + 10 mg\/kg Z944. The locomotor activity test was performed before the tests.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The results of right paw pressure test (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) and hot plate test (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.032) of CCI + Saline group, compared to the Saline group test results, confirmed the development of mechanical hyperalgesia and thermal hyperalgesia of the CCI + Saline group. The locomotor activities of Saline and other CCI groups were higher than the activity of CCI + 1 mg\/kg Atropine group (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.017). The dose-dependent increasing effect of Z944 in dose groups compared to the CCI + Saline group was determined, respectively, in the right paw pressure test (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.472,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.006,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) and the hot plate test (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.001,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001). The left paw pressure test results of CCI + Saline group and Z944 dose groups were not statistically different (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.995,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.159,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.110, respectively). Also, there were no statistically differences between the CCI + Saline and the CCI + 1 mg\/kg Atropine + 10 mg\/kg Z944 groups according to right paw pressure (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.945), left paw pressure (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.763), and hot plate (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.817) tests results.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    The attenuation of the analgesic effect of Z944 by the non-selective muscarinic receptor antagonist atropine suggests that the analgesic activity of Z944 may be mediated, at least in part, through muscarinic receptor-dependent mechanisms.\n                  <\/jats:p>","DOI":"10.5606\/agri.2026.95","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:31:27Z","timestamp":1792225887000},"page":"272-281","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the role of Z944 related to muscarinic receptors on hyperalgesia in rats"],"prefix":"10.5606","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2314-8126","authenticated-orcid":false,"given":"Meryem Dilek","family":"Acar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3874-633X","authenticated-orcid":false,"given":"\u00d6mer","family":"Bozduman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-6504","authenticated-orcid":false,"given":"Arzu","family":"Erdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3570","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"ref-1","doi-asserted-by":"crossref","unstructured":"Bourinet E, Altier C, Hildebrand ME, Trang T, Salter MW, Zamponi GW. Calcium-permeable ion channels in pain signaling. Physiol Rev 2014;94:81-140. doi: 10.1152\/physrev.00023.2013.","DOI":"10.1152\/physrev.00023.2013"},{"key":"ref-2","doi-asserted-by":"crossref","unstructured":"Zamponi GW, Striessnig J, Koschak A, Dolphin AC. The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol Rev 2015;67:821-70. doi: 10.1124\/pr.114.009654.","DOI":"10.1124\/pr.114.009654"},{"key":"ref-3","doi-asserted-by":"crossref","unstructured":"Bourinet E, Alloui A, Monteil A, Barr\u00e8re C, Couette B, Poirot O, et al. Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J 2005;24:315-24. doi: 10.1038\/sj.emboj.7600515.","DOI":"10.1038\/sj.emboj.7600515"},{"key":"ref-4","doi-asserted-by":"crossref","unstructured":"Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis. Lancet Neurol 2015;14:162-73. doi: 10.1016\/S1474-4422(14)70251-0.","DOI":"10.1016\/S1474-4422(14)70251-0"},{"key":"ref-5","doi-asserted-by":"crossref","unstructured":"Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008;70:1630-5. doi: 10.1212\/01.wnl.0000282763.29778.59.","DOI":"10.1212\/01.wnl.0000282763.29778.59"},{"key":"ref-6","doi-asserted-by":"crossref","unstructured":"Na HS, Choi S, Kim J, Park J, Shin HS. Attenuated neuropathic pain in Cav3.1 null mice. Mol Cells 2008;25:242-6.","DOI":"10.1016\/S1016-8478(23)17576-5"},{"key":"ref-7","doi-asserted-by":"crossref","unstructured":"Yue J, Liu L, Liu Z, Shu B, Zhang Y. Upregulation of T-type Ca2+ channels in primary sensory neurons in spinal nerve injury. Spine (Phila Pa 1976) 2013;38:463-70. doi: 10.1097\/BRS.0b013e318272fbf8.","DOI":"10.1097\/BRS.0b013e318272fbf8"},{"key":"ref-8","doi-asserted-by":"crossref","unstructured":"Khangura RK, Bali A, Kaur G, Singh N, Jaggi AS. Neuropathic pain attenuating effects of perampanel in an experimental model of chronic constriction injury in rats. Biomed Pharmacother 2017;94:557-63. doi: 10.1016\/j.biopha.2017.07.137.","DOI":"10.1016\/j.biopha.2017.07.137"},{"key":"ref-9","doi-asserted-by":"crossref","unstructured":"Verma S, Estanislao L, Simpson D. HIV-associated neuropathic pain: epidemiology, pathophysiology and management. CNS Drugs 2005;19:325-34. doi: 10.2165\/00023210-200519040-00005.","DOI":"10.2165\/00023210-200519040-00005"},{"key":"ref-10","doi-asserted-by":"crossref","unstructured":"Jaggi AS, Jain V, Singh N. Animal models of neuropathic pain. Fundam Clin Pharmacol 2011;25:1-28. doi: 10.1111\/j.1472- 8206.2009.00801.x.","DOI":"10.1111\/j.1472-8206.2009.00801.x"},{"key":"ref-11","doi-asserted-by":"crossref","unstructured":"Todorovic SM, Jevtovic-Todorovic V. Neuropathic pain: role for presynaptic T-type channels in nociceptive signaling. Pflugers Arch 2013;465:921-7. doi: 10.1007\/s00424-012-1211-y.","DOI":"10.1007\/s00424-012-1211-y"},{"key":"ref-12","doi-asserted-by":"crossref","unstructured":"Harding EK, Dedek A, Bonin RP, Salter MW, Snutch TP, Hildebrand ME. The T-type calcium channel antagonist, Z944, reduces spinal excitability and pain hypersensitivity. Br J Pharmacol 2021;178:3517- 32. doi: 10.1111\/bph.15498.","DOI":"10.1111\/bph.15498"},{"key":"ref-13","doi-asserted-by":"crossref","unstructured":"Ciotu CI, Fischer MJM. Novel analgesics with peripheral targets. Neurotherapeutics 2020;17:784-825. doi: 10.1007\/s13311-020- 00937-z.","DOI":"10.1007\/s13311-020-00937-z"},{"key":"ref-14","doi-asserted-by":"crossref","unstructured":"Gambeta E, Gandini MA, Souza IA, Zamponi GW. Ca V 3.2 calcium channels contribute to trigeminal neuralgia. Pain 2022;163:2315-25. doi: 10.1097\/j.pain.0000000000002651.","DOI":"10.1097\/j.pain.0000000000002651"},{"key":"ref-15","doi-asserted-by":"crossref","unstructured":"Platano D, Magli MC, Ferraretti AP, Gianaroli L, Aicardi G. L- and T-type voltage-gated Ca2+ channels in human granulosa cells: Functional characterization and cholinergic regulation. J Clin Endocrinol Metab 2005;90:2192-7. doi: 10.1210\/jc.2004-1819.","DOI":"10.1210\/jc.2004-1819"},{"key":"ref-16","doi-asserted-by":"crossref","unstructured":"Avery MC, Krichmar JL. Neuromodulatory systems and their interactions: A review of models, theories, and experiments. Front Neural Circuits 2017;11:108. doi: 10.3389\/fncir.2017.00108.","DOI":"10.3389\/fncir.2017.00108"},{"key":"ref-17","doi-asserted-by":"crossref","unstructured":"Kimura M, Saito S, Obata H. Dexmedetomidine decreases hyperalgesia in neuropathic pain by increasing acetylcholine in the spinal cord. Neurosci Lett 2012;529:70-4. doi: 10.1016\/j.neulet.2012.08.008.","DOI":"10.1016\/j.neulet.2012.08.008"},{"key":"ref-18","doi-asserted-by":"crossref","unstructured":"Zhang HM, Chen SR, Pan HL. Regulation of glutamate release from primary afferents and interneurons in the spinal cord by muscarinic receptor subtypes. J Neurophysiol 2007;97:102-9. doi: 10.1152\/jn.00586.2006.","DOI":"10.1152\/jn.00586.2006"},{"key":"ref-19","doi-asserted-by":"crossref","unstructured":"Hildebrand ME, David LS, Hamid J, Mulatz K, Garcia E, Zamponi GW, et al. Selective inhibition of Cav3.3 T-type calcium channels by Galphaq\/11-coupled muscarinic acetylcholine receptors. J Biol Chem 2007;282:21043-55. doi: 10.1074\/jbc.M611809200.","DOI":"10.1074\/jbc.M611809200"},{"key":"ref-20","doi-asserted-by":"crossref","unstructured":"Pemberton KE, Hill-Eubanks LJ, Jones SV. Modulation of lowthreshold T-type calcium channels by the five muscarinic receptor subtypes in NIH 3T3 cells. Pflugers Arch 2000;440:452-61. doi: 10.1007\/s004240000303.","DOI":"10.1007\/s004240000303"},{"key":"ref-21","doi-asserted-by":"crossref","unstructured":"Zhang Y, Zhang L, Wang F, Zhang Y, Wang J, Qin Z, et al. Activation of M3 muscarinic receptors inhibits T-type Ca(2+) channel currents via pertussis toxin-sensitive novel protein kinase C pathway in small dorsal root ganglion neurons. Cell Signal 2011;23:1057-67. doi: 10.1016\/j.cellsig.2011.02.001.","DOI":"10.1016\/j.cellsig.2011.02.001"},{"key":"ref-22","doi-asserted-by":"crossref","unstructured":"Zhang L, Zhang Y, Jiang D, Reid PF, Jiang X, Qin Z, et al. Alphacobratoxin inhibits T-type calcium currents through muscarinic M4 receptor and G\u03bf-protein \u03b2\u03b3 subunits-dependent protein kinase A pathway in dorsal root ganglion neurons. Neuropharmacology 2012;62:1062-72. doi: 10.1016\/j.neuropharm.2011.10.017.","DOI":"10.1016\/j.neuropharm.2011.10.017"},{"key":"ref-23","unstructured":"Ulixacaltamide - Praxis Precision Medicine. AdisInsight. Springer Nature Switzerland AG. Available from: https:\/\/adisinsight.springer. com\/drugs\/800035366 [Accessed: April 14, 2026]"},{"key":"ref-24","doi-asserted-by":"crossref","unstructured":"Scott L, Puryear CB, Belfort GM, Raines S, Hughes ZA, Matthews LG, et al. Translational pharmacology of PRAX-944, a novel T-type calcium channel blocker in development for the treatment of essential tremor. Mov Disord 2022;37:1193-201. doi: 10.1002\/mds.28969.","DOI":"10.1002\/mds.28969"},{"key":"ref-25","unstructured":"Praxis Precision Medicines. Praxis Precision Medicines announces positive topline results from two pivotal Phase 3 studies of ulixacaltamide HCl in the Essential3 program for essential tremor [press release]. 2025. Available from: https:\/\/investors. praxismedicines.com\/news-releases\/news-release-details\/praxisprecision-medicines-announces-positive-topline-results-1?utm_ source=chatgpt.com. [Accessed: January 13, 2026]"},{"key":"ref-26","unstructured":"Praxis Precision Medicines. Praxis Precision Medicines announces FDA acceptance of new drug application for ulixacaltamide HCl in patients with essential tremor [press release]. 2026 Apr 14. Available from: https:\/\/investors.praxismedicines.com\/news-releases\/ news-release-details\/praxis-precision-medicines-announces-fdaacceptance-new-drug [Accessed: April 21, 2026]"},{"key":"ref-27","doi-asserted-by":"crossref","unstructured":"Xia F, Du SZ, Wu MK, Liu R, Ye YS, Yang J, et al. Icetexane diterpenoids as Cav3.2 T-type calcium channel inhibitors from Salvia prattii and analgesic effect of their Semi-synthesized derivatives. Bioorg Chem 2022;128:106059. doi: 10.1016\/j.bioorg.2022.106059.","DOI":"10.1016\/j.bioorg.2022.106059"},{"key":"ref-28","doi-asserted-by":"crossref","unstructured":"Henbid MT, Marks WN, Collins MJ, Cain SM, Snutch TP, Howland JG. Sociability impairments in genetic absence epilepsy rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944. Exp Neurol 2017;296:16-22. doi: 10.1016\/j. expneurol.2017.06.022.","DOI":"10.1016\/j.expneurol.2017.06.022"},{"key":"ref-29","doi-asserted-by":"crossref","unstructured":"Pinardi G, Sierralta F, Miranda HF. Atropine reverses the antinociception of nonsteroidal anti-inflammatory drugs in the tail-flick test of mice. Pharmacol Biochem Behav 2003;74:603-8. doi: 10.1016\/s0091-3057(02)01046-8.","DOI":"10.1016\/S0091-3057(02)01046-8"},{"key":"ref-30","doi-asserted-by":"crossref","unstructured":"Naik AK, Tandan SK, Dudhgaonkar SP, Jadhav SH, Kataria M, Prakash VR, et al. Role of oxidative stress in pathophysiology of peripheral neuropathy and modulation by N-acetyl-L-cysteine in rats. Eur J Pain 2006;10:573-9. doi: 10.1016\/j.ejpain.2005.08.006.","DOI":"10.1016\/j.ejpain.2005.08.006"},{"key":"ref-31","doi-asserted-by":"crossref","unstructured":"Owoyele BV, Bakare AO, Ayinla MT, Adeshina KA, Onietan D, Azeez SO. Antinociceptive effects of lead acetate in sciatic nerve chronic constriction injury model of peripheral neuropathy in male Wistar rats. Naunyn Schmiedebergs Arch Pharmacol 2021;394:117-25. doi: 10.1007\/s00210-020-01951-w.","DOI":"10.1007\/s00210-020-01951-w"},{"key":"ref-32","doi-asserted-by":"crossref","unstructured":"Kukkar A, Singh N, Jaggi AS. Attenuation of neuropathic pain by sodium butyrate in an experimental model of chronic constriction injury in rats. J Formos Med Assoc 2014;113:921-8. doi: 10.1016\/j. jfma.2013.05.013.","DOI":"10.1016\/j.jfma.2013.05.013"},{"key":"ref-33","unstructured":"Hallak M, Balci H, G\u00fcnayd\u0131n C, Bilge SS. The role of muscarinic and serotonergic-2A receptors in the antinociceptive effect of pregabalin. Physiol Pharmacol 2019;23:302-8."},{"key":"ref-34","doi-asserted-by":"crossref","unstructured":"Rayiti RK, Munnangi SR, Bandarupalli R, Chakka V, Nimmagadda SL, Sk LS, et al. Effect of chrysin on mechanical hyperalgesia in chronic constriction injury-induced neuropathic pain in rat model. Int J Appl Basic Med Res 2020;10:189-93. doi: 10.4103\/ijabmr.IJABMR_58_19.","DOI":"10.4103\/ijabmr.IJABMR_58_19"},{"key":"ref-35","doi-asserted-by":"crossref","unstructured":"Weldon DT, O'Hare E, Kuskowski MA, Cleary J, Mach JR Jr. Alternating lever cyclic-ratio schedule analysis of the effects of atropine sulfate. Pharmacol Biochem Behav 1996;54:753-7. doi: 10.1016\/0091-3057(96)00014-7.","DOI":"10.1016\/0091-3057(96)00014-7"},{"key":"ref-36","doi-asserted-by":"crossref","unstructured":"Tringham E, Powell KL, Cain SM, Kuplast K, Mezeyova J, Weerapura M, et al. T-type calcium channel blockers that attenuate thalamic burst firing and suppress absence seizures. Sci Transl Med 2012;4:121ra19. doi: 10.1126\/scitranslmed.3003120.","DOI":"10.1126\/scitranslmed.3003120"},{"key":"ref-37","doi-asserted-by":"crossref","unstructured":"Antunes FTT, Huang S, Chen L, Zamponi GW. Effect of ABT639 on Cav3.2 channel activity and its analgesic actions in mouse models of inflammatory and neuropathic pain. Eur J Pharmacol 2024;967:176416. doi: 10.1016\/j.ejphar.2024.176416.","DOI":"10.1016\/j.ejphar.2024.176416"},{"key":"ref-38","doi-asserted-by":"crossref","unstructured":"Choi S, Yu E, Hwang E, Llin\u00e1s RR. Pathophysiological implication of CaV3.1 T-type Ca2+ channels in trigeminal neuropathic pain. Proc Natl Acad Sci U S A 2016;113:2270-5. doi: 10.1073\/ pnas.1600418113.","DOI":"10.1073\/pnas.1600418113"},{"key":"ref-39","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Caballero A, Gadotti VM, Stemkowski P, Weiss N, Souza IA, Hodgkinson V, et al. The deubiquitinating enzyme USP5 modulates neuropathic and inflammatory pain by enhancing Cav3.2 channel activity. Neuron 2014;83:1144-58. doi: 10.1016\/j. neuron.2014.07.036.","DOI":"10.1016\/j.neuron.2014.07.036"},{"key":"ref-40","doi-asserted-by":"crossref","unstructured":"Gomez K, Calder\u00f3n-Rivera A, Sandoval A, Gonz\u00e1lez-Ram\u00edrez R, Vargas-Parada A, Ojeda-Alonso J, et al. Cdk5-dependent phosphorylation of CaV3.2 T-Type channels: Possible role in nerve ligation-induced neuropathic allodynia and the compound action potential in primary afferent C fibers. J Neurosci 2020;40:283-96. doi: 10.1523\/JNEUROSCI.0181-19.2019.","DOI":"10.1523\/JNEUROSCI.0181-19.2019"},{"key":"ref-41","doi-asserted-by":"crossref","unstructured":"Li Y, Tatsui CE, Rhines LD, North RY, Harrison DS, Cassidy RM, et al. Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy. Pain 2017;158:417-29. doi: 10.1097\/j.pain.0000000000000774.","DOI":"10.1097\/j.pain.0000000000000774"},{"key":"ref-42","doi-asserted-by":"crossref","unstructured":"Jagodic MM, Pathirathna S, Joksovic PM, Lee W, Nelson MT, Naik AK, et al. Upregulation of the T-type calcium current in small rat sensory neurons after chronic constrictive injury of the sciatic nerve. J Neurophysiol 2008;99:3151-6. doi: 10.1152\/jn.01031.2007.","DOI":"10.1152\/jn.01031.2007"},{"key":"ref-43","doi-asserted-by":"crossref","unstructured":"Amorim JL, Lima FA, Brand ALM, Cunha S, Rezende CM, Fernandes PD. Two new \u03b2N-alkanoyl-5-hydroxytryptamides with relevant antinociceptive activity. Biomedicines 2021;9:455. doi: 10.3390\/ biomedicines9050455.","DOI":"10.3390\/biomedicines9050455"},{"key":"ref-44","doi-asserted-by":"crossref","unstructured":"Takasu K, Honda M, Ono H, Tanabe M. Spinal alpha(2)-adrenergic and muscarinic receptors and the NO release cascade mediate supraspinally produced effectiveness of gabapentin at decreasing mechanical hypersensitivity in mice after partial nerve injury. Br J Pharmacol 2006;148:233-44. doi: 10.1038\/sj.bjp.0706731.","DOI":"10.1038\/sj.bjp.0706731"},{"key":"ref-45","doi-asserted-by":"crossref","unstructured":"Pan YZ, Pan HL. Primary afferent stimulation differentially potentiates excitatory and inhibitory inputs to spinal lamina II outer and inner neurons. J Neurophysiol 2004;91:2413-21. doi: 10.1152\/ jn.01242.2003.","DOI":"10.1152\/jn.01242.2003"},{"key":"ref-46","doi-asserted-by":"crossref","unstructured":"Colangelo C, Shichkova P, Keller D, Markram H, Ramaswamy S. Cellular, synaptic and network effects of acetylcholine in the neocortex. Front Neural Circuits 2019;13:24. doi: 10.3389\/fncir.2019.00024.","DOI":"10.3389\/fncir.2019.00024"},{"key":"ref-47","doi-asserted-by":"crossref","unstructured":"Chen SR, Chen H, Yuan WX, Wess J, Pan HL. Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice. J Biol Chem 2014;289:14321-30. doi: 10.1074\/jbc.M114.550384.","DOI":"10.1074\/jbc.M114.550384"},{"key":"ref-48","doi-asserted-by":"crossref","unstructured":"Pan HL, Wu ZZ, Zhou HY, Chen SR, Zhang HM, Li DP. Modulation of pain transmission by G-protein-coupled receptors. Pharmacol Ther 2008;117:141-61. doi: 10.1016\/j.pharmthera.2007.09.003.","DOI":"10.1016\/j.pharmthera.2007.09.003"},{"key":"ref-49","doi-asserted-by":"crossref","unstructured":"Li DP, Chen SR, Pan YZ, Levey AI, Pan HL. Role of presynaptic muscarinic and GABA(B) receptors in spinal glutamate release and cholinergic analgesia in rats. J Physiol 2002;543:807-18. doi: 10.1113\/ jphysiol.2002.020644.","DOI":"10.1113\/jphysiol.2002.020644"},{"key":"ref-50","doi-asserted-by":"crossref","unstructured":"Zhang HM, Li DP, Chen SR, Pan HL. M2, M3, and M4 receptor subtypes contribute to muscarinic potentiation of GABAergic inputs to spinal dorsal horn neurons. J Pharmacol Exp Ther 2005;313:697- 704. doi: 10.1124\/jpet.104.079939.","DOI":"10.1124\/jpet.104.079939"},{"key":"ref-51","unstructured":"Rang HP, Dale MM, Ritter JM, Moore P. Pharmacology. 5th ed. Edinburgh: Elsevier; 2003."},{"key":"ref-52","doi-asserted-by":"crossref","unstructured":"Fiorino DF, Garcia-Guzman M. Muscarinic pain pharmacology: Realizing the promise of novel analgesics by overcoming old challenges. Handb Exp Pharmacol 2012;(208):191-221. doi: 10.1007\/978-3-642-23274-9_9.","DOI":"10.1007\/978-3-642-23274-9_9"},{"key":"ref-53","doi-asserted-by":"crossref","unstructured":"Yue CQ, Ye J, Li CL, Li RT, Sun Q. Antinociceptive effects of the novel spirocyclopiperazinium salt compound LXM-10 in mice. Pharmacol Biochem Behav 2007;86:643-50. doi: 10.1016\/j.pbb.2007.02.009.","DOI":"10.1016\/j.pbb.2007.02.009"},{"key":"ref-54","doi-asserted-by":"crossref","unstructured":"LeBlanc BW, Lii TR, Huang JJ, Chao YC, Bowary PM, Cross BS, et al. T-type calcium channel blocker Z944 restores cortical synchrony and thalamocortical connectivity in a rat model of neuropathic pain. Pain 2016;157:255-63. doi: 10.1097\/j. pain.0000000000000362.","DOI":"10.1097\/j.pain.0000000000000362"},{"key":"ref-55","doi-asserted-by":"crossref","unstructured":"Bourinet E, Zamponi GW. Voltage gated calcium channels as targets for analgesics. Curr Top Med Chem 2005;5:539-46. doi: 10.2174\/1568026054367610.","DOI":"10.2174\/1568026054367610"},{"key":"ref-56","doi-asserted-by":"crossref","unstructured":"Choi S, Na HS, Kim J, Lee J, Lee S, Kim D, et al. Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels. Genes Brain Behav 2007;6:425-31. doi: 10.1111\/j.1601-183X.2006.00268.x.","DOI":"10.1111\/j.1601-183X.2006.00268.x"},{"key":"ref-57","doi-asserted-by":"crossref","unstructured":"Bourinet E, Francois A, Laffray S. T-type calcium channels in neuropathic pain. Pain 2016;157:S15-22. doi: 10.1097\/j. pain.0000000000000469.","DOI":"10.1097\/j.pain.0000000000000469"},{"key":"ref-58","doi-asserted-by":"crossref","unstructured":"Mesnage B, Gaillard S, Godin AG, Rodeau JL, Hammer M, Von Engelhardt J, et al. Morphological and functional characterization of cholinergic interneurons in the dorsal horn of the mouse spinal cord. J Comp Neurol 2011;519:3139-58. doi: 10.1002\/cne.22668.","DOI":"10.1002\/cne.22668"},{"key":"ref-59","doi-asserted-by":"crossref","unstructured":"Cai YQ, Chen SR, Han HD, Sood AK, Lopez-Berestein G, Pan HL. Role of M2, M3, and M4 muscarinic receptor subtypes in the spinal cholinergic control of nociception revealed using siRNA in rats. J Neurochem 2009;111:1000-10. doi: 10.1111\/j.1471- 4159.2009.06396.x.","DOI":"10.1111\/j.1471-4159.2009.06396.x"},{"key":"ref-60","doi-asserted-by":"crossref","unstructured":"Zhang J, Chen SR, Chen H, Pan HL. RE1-silencing transcription factor controls the acute-to-chronic neuropathic pain transition and Chrm2 receptor gene expression in primary sensory neurons. J Biol Chem 2018;293:19078-91. doi: 10.1074\/jbc.RA118.005846.","DOI":"10.1074\/jbc.RA118.005846"},{"key":"ref-61","doi-asserted-by":"crossref","unstructured":"Hayashida KI, Bynum T, Vincler M, Eisenach JC. Inhibitory M2 muscarinic receptors are upregulated in both axotomized and intact small diameter dorsal root ganglion cells after peripheral nerve injury. Neuroscience 2006;140:259-68. doi: 10.1016\/j. neuroscience.2006.02.013.","DOI":"10.1016\/j.neuroscience.2006.02.013"},{"key":"ref-62","doi-asserted-by":"crossref","unstructured":"Taylor BK. Spinal inhibitory neurotransmission in neuropathic pain. Curr Pain Headache Rep 2009;13:208-14. doi: 10.1007\/s11916-009- 0035-8.","DOI":"10.1007\/s11916-009-0035-8"},{"key":"ref-63","doi-asserted-by":"crossref","unstructured":"Tata AM, Vilar\u00f3 MT, Mengod G. Muscarinic receptor subtypes expression in rat and chick dorsal root ganglia. 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