Article Data

  • Views 427
  • Dowloads 50

Original Research

Open Access

Pregabalin Reduces Acute Inflammatory and Persistent Pain Associated with Nerve Injury and Cancer in Rat Models of Orofacial Pain

  • Wagner Hummig1
  • Caroline Machado Kopruszinski1
  • Juliana Geremias Chichorro1,*,

1Pharmacology Postgraduate Program, Federal University of Paraná, Curitiba, Paraná, Brazil

DOI: 10.11607/ofph.1317 Vol.28,Issue 4,December 2014 pp.350-359

Published: 30 December 2014

*Corresponding Author(s): Juliana Geremias Chichorro E-mail: juliana.chichorro@ufpr.br

Abstract

Aims: To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. Methods: Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. Results: Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. Conclusion: Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

Keywords

cancer; inflammatory pain; infraorbital nerve constriction; pregabalin; trigeminal pain

Cite and Share

Wagner Hummig,Caroline Machado Kopruszinski,Juliana Geremias Chichorro. Pregabalin Reduces Acute Inflammatory and Persistent Pain Associated with Nerve Injury and Cancer in Rat Models of Orofacial Pain. Journal of Oral & Facial Pain and Headache. 2014. 28(4);350-359.

References

1. Dooley DJ, Taylor CP, Donevan S, Feltner D. Ca2+ channel alfa 2 delta ligands: Novel modulators of neurotransmission. Trends Pharmacol Sci 2007;28:75–82.

2. Stahl SM, Porreca F, Taylor CP, Cheung R, Thorpe AJ, Clair A. The diverse therapeutic actions of pregabalin: Is a single mechanism responsible for several pharmacological activities? Trends Pharmacol Sci 2013;34:332–339.

3. Jones DL, Sorkin LS. Systemic gabapentin and S(+)-3-isobutyl-gamma-aminobutyric acid block secondary hyperal-gesia. Brain Res 1998;810:93–99.

4. Qin N, Olcese R, Stefani E, Birnbaumer L. Modulation of human neuronal alpha1E-type calcium channel by alpha 2 del-ta-subunit. Am J Physiol 1998;274:C1324–C1331.

5. Wyatt CN, Page KM, Berrow NS, Brice NL, Dolphin AC. The effect of over expression of auxiliary Ca2+ channel subunits on native Ca2+ channel currents in undifferentiated mammalian NG108-15 cells. J Physiol 1998;510:347–360.

6. Barclay J, Balaguero N, Mione M, et al. Ducky mouse pheno-type of epilepsy and ataxia is associated with mutations in the Cacna2d2 gene and decreased calcium channel current in cerebellar Purkinje cells. J Neurosci 2001;21:6095–6104.

7. Klugbauer N, Marais E, Hofmann F. Calcium channel alpha2delta subunits: Differential expression, function, and drug binding. J Bioenerg Biomembr 2003;35:639–647.

8. Cantí C, Nieto-Rostro M, Foucault I, et al. The metalion-dependent adhesion site in the Von Willebrand factor-A domain of alpha2delta subunits is key to trafficking voltage-gated Ca2+ channels. Proc Natl Acad Sci USA 2005;102:11230–11235.

9. Bauer CS, Nieto-Rostro M, Rahman W, et al. The increased trafficking of the calcium channel subunit α2δ-1 to presynaptic terminals in neuropathic pain is inhibited by the α2δ ligand pregabalin. J Neurosci 2009;29:4076–4088.

10. Frampton JE, Foster RH. Pregabalin: In the treatment of post–herpetic neuralgia. Drugs 2005;65:111–118.

11. Freeman R, Durso-Decruz E, Emir B. Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: Findings from seven randomized, controlled trials across a range of doses. Diabetes Care 2008;31:1448–1454.

12. Cappuzzo KA. Treatment of postherpetic neuralgia: Focus on pregabalin. Clin Interv Aging 2009;4:17–23.

13. Cardenas DD, Nieshoff EC, Suda K, et al. A randomized trial of pregabalin in patients with neuropathic pain due to spinal cord injury. Neurology 2013;80:533–539.

14. Parsons B, Sanin L, Yang R, Emir B, Juhn M. Efficacy and safety of pregabalin in patients with spinal cord injury: A pooled analysis. Curr Med Res Opin 2013;29:1675–1683.

15. Obermann M, Yoon MS, Sensen K, Maschke M, Diener HC, Katsarava Z. Efficacy of pregabalin in the treatment of trigeminal neuralgia. Cephalalgia 2008;28:174–181.

16. Pérez C, Saldaña MT, Navarro A, Martínez S, Rejas J. Trigeminal neuralgia treated with pregabalin in family medicine settings: Its effect on pain alleviation and cost reduction. J Clin Pharmacol 2009;49:582–590.

17. Newton RA, Bingham S, Case PC, Sanger GJ, Lawson SN. Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury. Brain Res Mol Brain Res 2001;95:1–8.

18. Wang H, Sun H, Della PK, et al. Chronic neuropathic pain is accompanied by global changes in gene expression and shares pathobiology with neurodegenerative diseases. Neuroscience 2002;114:529–546.

19. Li CY, Song YH, Higuera ES, Luo ZD. Spinal dorsal horn calcium channel α2δ-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci 2004;24: 8494–8499.

20. Yokoyama T, Maeda Y, Audette KM, Sluka KA. Pregabalin reduces muscle and cutaneous hyperalgesia in two models of chronic muscle pain in rats. J Pain 2007;8:422–429.

21. Million M, Wang L, Adelson DW, Roman F, Diop L, Taché Y. Pregabalin decreases visceral pain and prevents spinal neuronal activation in rats. Gut 2007;56:1482–1484.

22. Łuszczki JJ. Dose-response relationship analysis of pregabalin doses and their antinociceptive effects in hotplate test in mice. Pharmacol Rep 2010;62:942–948.

23. Bannister K, Sikandar S, Bauer CS, Dolphin AC, Porreca F, Dickenson AH. Pregabalin suppresses spinal neuronal hyper-excitability and visceral hypersensitivity in the absence of peripheral pathophysiology. Anesthesiology 2011;115:144–152.

24. Kweon TD, Kim JY, Kwon IW, Choi JB, Lee YW. Participation of K(ATP) Channels in the Antinociceptive Effect of Pregabalin in Rat Formalin Test. Korean J Pain 2011;24:131–136.

25. Houghton LA, Fell C, Whorwell PJ, Jones I, Sudworth DP, Gale JD. Effect of a second-generation alpha2delta ligand (pregab-alin) on visceral sensation in hypersensitive patients with irritable bowel syndrome. Gut 2007;56:1218–1225.

26. Chizh BA, Göhring M, Tröster A, Quartey GK, Schmelz M, Koppert W. Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers. Br J Anaesth 2007;98:246–254.

27. Wang H, Bolognese J, Calder N, et al. Effect of morphine and pregabalin compared with diphenhydramine hydrochlo-ride and placebo on hyperalgesia and allodynia induced by intradermal capsaicin in healthy male subjects. J Pain 2008; 9:1088–1095.

28. Altis K, Schmidtko A, Angioni C, et al. Analgesic efficacy of tramadol, pregabalin and ibuprofen in menthol-evoked cold hyperalgesia. Pain 2009;147:116–121.

29. Olesen SS, Bouwense SA, Wilder-Smith OH, van Goor H, Drewes AM. Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial. Gastroenterology 2011;141:536–543.

30. Bouwense SA, Olesen SS, Drewes AM, Poley JW, van Goor H, Wilder-Smith OH. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial. PLoS One 2012;7:e42096.

31. Narita N, Kumar N, Cherkas PS, et al. Systemic pregabalin attenuates sensorimotor responses and medullary glutamate release in inflammatory tooth pain model. Neuroscience 2012; 218:359–366.

32. Pelisser T, Pajot J, Dallel R. The orofacial capsaicin test in rats: Effects of different capsaicin concentrations and morphine. Pain 2002;96:81–87.

33. Dallel R, Raboisson P, Clavelou P, Saade M, Woda A. Evidence for a peripheral origin of the tonic nociceptive response to subcutaneous formalin. Pain 1995;61:11–16.

34. Capuano A, De Corato A, Treglia M, Tringali G, Dello Russo C, Navarra P. Antinociceptive activity of buprenorphine and lumiracoxib in the rat orofacial formalin test: A combination analysis study. Eur J Pharmacol 2009;605:57–62.

35. Vos BP, Strassman AM, Maciewicz RJ. Behavioral evidence of trigeminal neuropathic pain following chronic constriction injury in rats infraorbital nerve. J Neurosci 1994;14:2708–2723.

36. Chichorro JG, Zampronio AR, Souza GE, Rae GA. Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in rats: Reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs. Pain 2006;123:64–74.

37. Chichorro JG, Zampronio AR, Cabrini DA, Franco CR, Rae GA. Mechanisms operated by endothelin ETA and ETB receptors in the trigeminal ganglion contribute to orofacial thermal hyperalgesia induced by infraorbital nerve constriction in rats. Neuropeptides 2009;43:133–142.

38. Ono K, Harano N, Inenaga K, Nakanishi O. A rat pain model of facial cancer. Methods Mol Biol 2012;851:149–157.

39. Harano N, Ono K, Hidaka K, Kai A, Nakanishi O, Inenaga K. Differences between orofacial inflammation and cancer pain. J Dent Res 2010;89:615–620.

40. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983;16:109–110.

41. Chichorro JG, Lorenzetti BB, Zampronio AR. Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats. Br J Pharmacol 2004;141:1175–1184.

42. Nagahata S, Harano N, Shiiba S, Nakanishi O. A rat model for cancer pain in the trigeminal nerve area. J Jpn Dent Soc Anesthesiol 2007;35:21–28.

43. Ono K, Harano N, Nagahata S, Seta Y, Tsujisawa T, Inenaga K, Nakanishi O. Behavioral characteristics and c-Fos expression in the medullary dorsal horn in a rat model for orofacial cancer pain. Eur J Pain 2009;13:373–379.

44. Brigatte P, Sampaio SC, Gutierrez VP, et al. Walker 256 tumor-bearing rats as a model to study cancer pain. J Pain 2007; 8:412–421.

45. Nones CF, Reis RC, Jesus CH, Veronez DA, Cunha JM, Chichorro JG. Orofacial sensory changes after streptozotocin-induced diabetes in rats. Brain Res 2013;1501:56–67.

46. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharma-codynamics of pregabalin and gabapentin. Clin Pharmacokinet 2010;49:661–669.

47. Miyazaki R, Yamamoto T. The efficacy of morphine, pregabalin, gabapentin, and duloxetine on mechanical allodynia is different from that on neuroma pain in the rat neuropathic pain model. Anesth Analg 2012;115:182–188.

48. Glare PA, Walsh TD. Clinical pharmacokinetics of morphine. Ther Drug Monit 1991;13:1–23.

49. Kobayashi K, Fukuoka T, Obata K, et al. Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta/c-fibers and colocalization with trk receptors. J Comp Neurol 2005;493:596–606.

50. Fehrenbacher JC, Taylor CP, Vasko MR. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain 2003;105:133–141.

51. Field MJ, Cox PJ, Stott E, et al. Identification of the alpha2-del-ta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci 2006;103:17537–17542.

52. Bardin L, Gregoire S, Aliaga M, et al. Comparison of milnacipran, duloxetine and pregabalin in the formalin pain test and in a model of stress-induced ultrasonic vocalizations in rats. Neurosci Res 2010;66:135–140.

53. Tjølsen A, Berge OG, Hunskaar S, Rosland JH, Hole K. The formalin test: An evaluation of the method. Pain 1992;51:5–17.

54. Clavelou P, Pajot J, Dallel R, Raboisson P. Application of formalin test to study of orofacial pain in the rat. Neurosci Lett 1989;103:349–353.

55. Padi SS, Naidu PS, Kulkarni SK. Involvement of peripheral prostaglandins in formalin-induced nociceptive behaviours in the orofacial area of rats. Inflammopharmacology 2006;14:57–61.

56. Bannister K, Sikandar S, Bauer CS, Dolphin AC, Porreca F, Dickenson AH. Pregabalin suppresses spinal neuronal hyper-excitability and visceral hypersensitivity in the absence of peripheral pathophysiology. Anesthesiology 2011;115:144–152.

57. Aley KO, Messing RO, Mochly-Rosen D, Levine JD. Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the e isozyme of protein kinase C. J Neurosci 2000;20: 4680–4685.

58. Roberts J, Ossipov MH, Porreca F. Glial activation in the rostroventromedial medulla promotes descending facilitation to mediate inflammatory hypersensitivity. Eur J Neurosci 2009; 30:229–241.

59. Mitsikostas DD, Knight YE, Lasalandra M, Kavantzas N, Goadsby PJ. Triptans attenuate capsaicin-induced CREB phosphorylation within the trigeminal nucleus caudalis: A mechanism to prevent central sensitization? J Headache Pain 2011;12:411–417.

60. Villarreal CF, Funez MI, Cunha Fde Q, Parada CA, Ferreira SH. The long-lasting sensitization of primary afferent nociceptors induced by inflammation involves prostanoid and dopaminergic systems in mice. Pharmacol Biochem Behav 2013; 103:678–683.

61. Latremoliere A, Woolf CJ. Central sensitization: A generator of pain hypersensitivity by central neural plasticity. J Pain 2009;10:895–926.

62. Kumar N, Cherkas PS, Varathan V, et al. Systemic prega-balin attenuates facial hypersensitivity and noxious stimulus-evoked release of glutamate in medullary dorsal horn in a rodent model of trigeminal neuropathic pain. Neurochem Int 2013;62:831–835.

63. Cao Y, Wang H, Chiang CY, Dostrovsky JO, Sessle BL. Pregabalin suppresses nociceptive behavior and central sensitization in a rat trigeminal neuropathic pain model. J Pain 2013;14:193–204.

64. Bennett MI, Laird B, van Litsenburg C, Nimour M. Pregabalin for the management of neuropathic pain in adults with cancer: A systematic review of the literature. Pain Med 2013;14:1681–1688.

65. Epstein JB, Wilkie DJ, Fischer DJ, Kim YO, Villines D. Neuropathic and nociceptive pain in head and neck cancer patients receiving radiation therapy. Head Neck Oncol 2009;1:26.

66. Nishihara M, Arai YC, Yamamoto Y, et al. Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants to opioids for intractable painful bone metastases. Pain Physician 2013;16:E547–E552.

67. Raptis E, Vadalouca A, Stavropoulou E, Argyra E, Melemeni A, Siafaka I. Pregabalin vs. opioids for the treatment of neuropathic cancer pain: A prospective, head-to-head, randomized, open-label study. Pain Pract 2014;14:32–42.

68. Hidaka K, Ono K, Harano N, et al. Central glial activation mediates cancer-induced pain in a rat facial cancer model. Neuroscience 2011;180:334–343.

69. Le Resche L. Epidemiology of temporomandibular disorders: Implications for the investigation of etiologic factors. Crit Rev Oral Biol Med 1997;8:291–305.

70. Eide PK, Rabben T. Trigeminal neuropathic pain: Patho-physiological mechanisms examined by quantitative assessment of abnormal pain and sensory perception. Neurosurgery 1998;43:1103–1110.

71. Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994; 330:592–596.

72. Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S. Symptoms during cancer pain treatment following WHO-guidelines: A longitudinal follow-up study of symptom prevalence, severity and etiology. Pain 2001;93:247–257.

73. Kumar K, Laferriere A, Yu JS, Leavitt A, Coderre TJ. Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. J Neurochem 2010;113:552–561.

74. Yang F, Whang J, Derry WT, Vardeh D, Scholz J. Analgesic treatment with pregabalin does not prevent persistent pain after peripheral nerve injury in the rat. Pain 2014;155:356–366.

75. Gustafsson H, Sandin J. Oral pregabalin reverses cold allodynia in two distinct models of peripheral neuropathic pain. Eur J Pharmacol 2009;605:103–108.

Abstracted / indexed in

Science Citation Index (SCI)

Science Citation Index Expanded (SCIE)

BIOSIS Previews

Scopus

Cumulative Index to Nursing and Allied Health Literature (CINAHL)

Submission Turnaround Time

Conferences

Top