Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

Document Type: Original Article

Authors

1 Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran

2 Department of Toxicology and Pharmacology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Oral and Maxillofacial Surgery, School of Dentistry, Mazandaran University of Medical Science, Sari, Iran

4 School of Pharmacy, International Branch, Shiraz University of Medical Sciences, Shiraz, Iran

5 Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran

Abstract

Objective(s): Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception.
Materials and Methods: Paclitaxel (2 mg/kg IP) was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia.
Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO) did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO) administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist.
Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

Keywords


1. Landowski LM, Dyck PJ, Engelstad J, Taylor BV. Axonopathy in peripheral neuropathies: Mechanisms and therapeutic approaches for regeneration. J Chem Neuroanat. 2016; 76(Pt A):19-27

2. Scripture CD, Figureg WD, Sparreboom A. Peripheral neuropathy induced by paclitaxel: recent insights and future perspectives. Curr Neuropharmacol  2006; 4:165-172.

3. Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol  2014; 32:1941-1967.

4. Albers JW, Chaudhry V, Cavaletti G, Donehower RC. Interventions for preventing neuropathy caused by cisplatin and related compounds. Cochrane Database Syst Rev 2014; 31:CD005228.

5. Xiao W, Boroujerdi A, Bennett GJ, Luo ZD. Chemotherapy-evoked painful peripheral neuropathy: analgesic effects of gabapentin and effects on expression of the alpha-2-  delta type-1 calcium channel subunit. Neuroscience  2007;144:714-720.

6. Nihei S, Sato J, Kashiwaba M, Itabashi T, Kudo K, Takahashi K. Efficacy and safety of pregabalin for oxaliplatin- and paclitaxel-induced peripheral neuropathy. Gan To Kagaku Ryoho 2013;40:1189-93.

7. Kaley TJ, Deangelis LM. Therapy of chemotherapy-induced peripheral neuropathy. Br J Haematol 2009;145:3-14.

8. Aziz MT, Good BL, Lowe DK. Serotonin-norepinephrine reuptake inhibitors for the management of chemotherapy-induced peripheral neuropathy. Ann Pharmacother, 2014;48: 626-632.

9. Seidel S, Aigner M, Ossege M, Pernicka E, Wildner B, Sycha T. Antipsychotics for acute and chronic pain in adults. Cochrane Database Syst Rev 2013; 29:CD004844.

10. Cohrs S. Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics. CNS Drugs 2008; 22:939-962.

11. Roberts RJ, Lohano KK, El-Mallakh RS. Antipsychotics as antidepressants. Asia Pac Psychiatry. 2016; 8:179-188.

12. Nishiyama A, Matsumoto H. Quetiapine reduces irritability and risk of suicide in patients with agitated depression. Tokai J Exp Clin Med 2013; 38:93-96.

13. Kondo MA, Tajinda K, Colantuoni C, Hiyama H, Seshadri S, Huang B, et al. Unique pharmacological actions of atypical neuroleptic quetiapine: possible role in cell cycle/fate control. Transl Psychiatry 2013; 3:e243.

14. Tokunaga A, Saika M, Senba E. 5-HT2A receptor subtype is involved in the thermal hyperalgesic mechanism of serotonin in the periphery. Pain 1998; 76:349-355.

15. Zhang JM, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin 2007; 45:27-37.

16. Sugino H, Futamura T, Mitsumoto Y, Maeda K, Marunaka Y. Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33:303-307.

17. Bian Q, Kato T, Monji A, Hashioka S, Mizoguchi Y, Horikawa H, Kanba S. The effect of atypical antipsychotics, perospirone, ziprasidone and quetiapine on microglial activation induced by interferon-gamma. Prog Neuro -psychopharmacol Biol Psychiatry 2008; 32:42-48.

18. Calandre EP, Rico-Villademoros F. The role of anti - psychotics in the management of fibromyalgia. CNS Drugs 2012; 26:135-53.

19. Seeman P. Atypical antipsychotics: mechanism of action. Can J Psychiatry  2002;47:27-38.

20. Hajhashemi V, Banafshe HR, Minaiyan M, Mesdaghinia A, Abed A. Antinociceptive effects of venlafaxine in a rat model of peripheral neuropathy: role of alpha2- adrenergic receptors. Eur J Pharmacol  2014; 738:230-236.

21. Naji-Esfahani H, Vaseghi G, Safaeian L, Pilehvarian AA, Abed A, Rafieian-Kopaei M. Gender differences in a mouse model of chemotherapy-induced neuropathic pain. Lab Anim 2016; 50:15-20.

22. Nieto FR, Entrena JM, Cendán CM, Pozo ED, Vela JM, Baeyens JM. Tetrodotoxin inhibits the development and expression of neuropathic pain induced by paclitaxel in mice. Pain 2008;137:520-531.

23. Kim H, Bang J, Chang HW, Kim JY, Park KU, Kim SH, Lee KJ, Cho CH, Hwang I, Park SD, Ha E, Jung SW. Anti-inflammatory effect of quetiapine on collagen-induced arthritis of mouse. Eur J Pharmacol 2012; 678:55-60.

24. Banafshe HR, Hajhashemi V, Minaiyan M, Mesdaghinia A, Abed A. Antinociceptive effects of maprotiline in a rat model of peripheral neuropathic pain: possible involvement of opioid system. Iran J Basic Med Sci 2015;18:752-7.

25. Abed A, Hajhashemi V, Banafshe HR, Minaiyan M, Mesdaghinia A. Venlafaxine attenuates heat hyperalgesia independent of adenosine or opioid system in a rat model of peripheral neuropathy. Iran J Pharm Res 2015; 14:843-50.

26. Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of painsensation like those seen in man.Pain. 1988; 33:87-107.

27. Hamidi GA, Jafari-Sabet M, Abed A, Mesdaghinia A, Mahlooji M, Banafshe HR. Gabapentin enhances anti-nociceptive effects of morphine on heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain. Iran J Basic Med Sci  2014; 17:753-9.

28. Brzeziński K. Chemotherapy-induced polyneuropathy. Part I. Pathophysiology. Contemp Oncol (Pozn) 2012; 16:72-78.

29. Carozzi VA, Canta A, Chiorazzi A. Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms? Neurosci Lett  2015; 596:90-107.

30. Sisignano M, Baron R, Scholich K, Geisslinger G. Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain. Nat Rev Neurol 2014; 10:694-707.

31. Dumontet C, Jordan MA. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 2010; 9:790-803.

32. Boyette-Davis JA, Walters ET, Dougherty PM. Mechanisms involved in the development of chemotherapy-induced neuropathy. Pain Manag 2015; 5:285-296.

33. Pollmächer T, Haack M, Schuld A, Kraus T, Hinze-Selch D. Effects of antipsychotic drugs on cytokine networks. J Psychiatr Res 2000; 34:369-382.

34. Kato TA, Monji A, Mizoguchi Y, Hashioka S, Horikawa H, Seki Y, Kasai M, Utsumi H, Kanba S. Anti-Inflammatory properties of antipsychotics via microglia modulations: are antipsychotics a 'fire extinguisher' in the brain of schizophrenia? Mini Rev Med Chem 2011; 11: 565-574.

35. Luo XG, Chen SD. The changing phenotype of microglia from homeostasis to disease. Transl Neurodegener  2012;1:9-14.

36. Janes K, Little JW, Li C, Bryant L, Chen C, Chen Z, Kamocki K, Doyle T, Snider A, Esposito E, Cuzzocrea S, Bieberich E, Obeid L, Petrache I, Nicol G, Neumann WL, Salvemini D. The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1. J Biol Chem  2014; 289:21082-21097.

37. Fregnan F, Muratori L, Simões AR, Giacobini-Robecchi MG, Raimondo S. Role of inflammatory cytokines in peripheral nerve injury. Neural Regen Res 2012;7:2259-2266.

38. Wang F, Stefano GB, Kream RM. Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: etiological contribution to complex regional pain syndromes (Part I). Med Sci Monit 2014;20:1067-1077.

39. Okamoto K, Imbe H, Morikawa Y, Itoh M, Sekimoto M, Nemoto K, Senba E. 5-HT2A receptor subtype in the peripheral
branch of sensory fibers is involved in the potentiation of inflammatory pain in rats. Pain 2002;99:133-143.

40. Rahman W, Bannister K, Bee LA, Dickenson AH. A pronociceptive role for the 5- HT2 receptor on spinal nociceptive transmission: an in vivo electrophysiological study in the rat. Brain Res 2011; 1382:29-36.

41. Tascedda F, Lovati E, Blom JM, Muzzioli P, Brunello N, Racagni G, Riva MA. Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic seroquel (quetiapine fumarate). Neuropsycho-pharmacology. 1999; 21: 211-217.

42. Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. Ndesalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity. Neuropsycho- pharmacology 2008;33: 2303- 2312.

43. López-Muñoz F, Alamo C. Active metabolites as antidepressant drugs: the role of norquetiapine in the mechanism of action of quetiapine in the treatment of mood disorders. Front Psychiatry 2013; 4:102-107.

44. Jeong HJ, Mitchell VA, Vaughan CW. Role of 5-HT(1) receptor subtypes in the modulation of pain and synaptic transmission in rat spinal superficial dorsal horn. Br J Pharmacol 2012;165: 1956-1965.

45. Ossipov MH, Morimura K, Porreca F. Descending pain modulation and chronification of pain. Curr Opin Support Palliat Care 2014; 8:143-151.

46. Smith H, Elliott J. Alpha(2) receptors and agonists in pain management. Curr Opin Anaesthesiol 2001; 14:513-518.

47. Kawasaki Y, Kumamoto E, Furue H, Yoshimura M. Alpha 2 adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantiagelatinosa neurons. Anesthesiology 2003; 98:682-689.

48. Kingery WS, Agashe GS, Guo TZ, Sawamura S, Davies MF, Clark JD, et al. Isoflurane and nociception: spinal alpha2A adrenoceptors mediate antinociception while supraspinal alpha1 adrenoceptors mediate pronociception. Anesthesiology  2002; 96:367-374.