Lasers in Medical Science

, Volume 34, Issue 3, pp 517–523 | Cite as

The effect of photobiomodulation on total amount of substance P in gingival crevicular fluid: placebo-controlled randomized clinical trial

  • Ezgi Doğanay YıldızEmail author
  • Hakan Arslan
  • Serhat Köseoğlu
  • Taner Arabacı
  • Dursun Anıl Yıldız
  • Levent Savran
Original Article


To investigate the effect of photobiomodulation (PBM) and placebo on total amount of substance P in gingival crevicular fluid (GCF) pre- and postoperatively. Twenty-six patients having tooth with symptomatic apical periodontitis were enrolled in this study. GCF was collected preoperatively. The patients were assigned into two groups (n = 13), as follows: placebo and PBM. Sampling was repeated 7 days after root canal treatment. Two independent samples T test was used for analyzing of the differences between preoperative and postoperative substance P levels in GCF (p = .05). The Pearson correlation analysis was used for determination of correlation among substance P levels and other variables. For placebo group, there is no significant difference between preoperative and postoperative total amounts of substance P level (p = 0.553). For PBM group, postoperative total amount of substance P level was significantly higher than those of preoperative level (p = 0.005). Within the limitation of the present study, PBM has immunomodulation effect linked to the modulation of the total amount of substance P in the gingival crevicular fluid. Thai Clinical Trials Registry: TCTR20161228002


Substance P Photobiomodulation Postoperative pain Gingival crevicular fluid 



The work was supported by the Department of Endodontics, Erzurum, Turkey.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Payer M, Jakse N, Pertl C, Truschnegg A, Lechner E, Eskici A (2005) The clinical effect of LLLT in endodontic surgery: a prospective study on 72 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100:375–379. CrossRefGoogle Scholar
  2. 2.
    Aras MH, Gungormus M (2009) The effect of low-level laser therapy on trismus and facial swelling following surgical extraction of a lower third molar. Photomed Laser Surg 27:21–24. CrossRefGoogle Scholar
  3. 3.
    Abreu ME, Viegas VN, Pagnoncelli RM et al (2010) Infrared laser therapy after surgically assisted rapid palatal expansion to diminish pain and accelerate bone healing. World J Orthod 11:273–277Google Scholar
  4. 4.
    Fikackova H, Dostalova T, Navratil L, Klaschka J (2007) Effectiveness of low-level laser therapy in temporomandibular joint disorders: a placebo-controlled study. Photomed Laser Surg 25:297–303. CrossRefGoogle Scholar
  5. 5.
    Noda M, Aoki A, Mizutani K et al (2016) High-frequency pulsed low-level diode laser therapy accelerates wound healing of tooth extraction socket: an in vivo study. Lasers Surg Med.
  6. 6.
    Bhardwaj S, George JP, Remigus D, Khanna D (2016) Low level laser therapy in the treatment of intra-osseous defect—a case report. J Clin Diagn Res 10:ZD06–ZF08. Google Scholar
  7. 7.
    Karu T (2010) Mitochondrial mechanisms of photobiomodulation in context of new data about multiple roles of ATP. Photomed Laser Surg 28:159–160. CrossRefGoogle Scholar
  8. 8.
    Antunes F, Boveris A, Cadenas E (2004) On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide. Proc Natl Acad Sci U S A 101:16774–16779. CrossRefGoogle Scholar
  9. 9.
    Lim W, Kim J, Kim S et al (2013) Modulation of lipopolysaccharide-induced NF-kappaB signaling pathway by 635 nm irradiation via heat shock protein 27 in human gingival fibroblast cells. Photochem Photobiol 89:199–207. CrossRefGoogle Scholar
  10. 10.
    de Lima FM, Albertini R, Dantas Y et al (2013) Low-level laser therapy restores the oxidative stress balance in acute lung injury induced by gut ischemia and reperfusion. Photochem Photobiol 89:179–188. CrossRefGoogle Scholar
  11. 11.
    Gibran NS, Jang YC, Isik FF et al (2002) Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. J Surg Res 108:122–128CrossRefGoogle Scholar
  12. 12.
    Richardson JD, Vasko MR (2002) Cellular mechanisms of neurogenic inflammation. J Pharmacol Exp Ther 302:839–845. CrossRefGoogle Scholar
  13. 13.
    Harrison S, Geppetti P (2001) Substance P. Int J Biochem Cell Biol 33:555–576CrossRefGoogle Scholar
  14. 14.
    Snijdelaar DG, Dirksen R, Slappendel R, Crul BJ (2000) Substance P. Eur J Pain 4:121–135. CrossRefGoogle Scholar
  15. 15.
    Siqueira JF Jr, Rocas IN, Favieri A et al (2002) Incidence of postoperative pain after intracanal procedures based on an antimicrobial strategy. J Endod 28:457–460. CrossRefGoogle Scholar
  16. 16.
    Park CK, Bae JH, Kim HY et al (2010) Substance P sensitizes P2X3 in nociceptive trigeminal neurons. J Dent Res 89:1154–1159. CrossRefGoogle Scholar
  17. 17.
    Vishwanath R, Mukherjee R (1996) Substance P promotes lymphocyte-endothelial cell adhesion preferentially via LFA-1/ICAM-1 interactions. J Neuroimmunol 71:163–171CrossRefGoogle Scholar
  18. 18.
    Kant V, Gopal A, Kumar D et al (2013) Topically applied substance P enhanced healing of open excision wound in rats. Eur J Pharmacol 715:345–353. CrossRefGoogle Scholar
  19. 19.
    Benrath J, Zimmermann M, Gillardon F (1995) Substance P and nitric oxide mediate would healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation. Neurosci Lett 200:17–20CrossRefGoogle Scholar
  20. 20.
    Burssens P, Steyaert A, Forsyth R, van Ovost EJ, Depaepe Y, Verdonk R (2005) Exogenously administered substance P and neutral endopeptidase inhibitors stimulate fibroblast proliferation, angiogenesis and collagen organization during Achilles tendon healing. Foot Ankle Int 26:832–839CrossRefGoogle Scholar
  21. 21.
    Levrini L, Sacerdote P, Moretti S, Panzi S, Caprioglio A (2013) Changes of substance P in the crevicular fluid in relation to orthodontic movement preliminary investigation. Scientific World Journal 2013:896874. CrossRefGoogle Scholar
  22. 22.
    Chapple IL, Cross IA, Glenwright HD, Matthews JB (1995) Calibration and reliability of the Periotron 6000 for individual gingival crevicular fluid samples. J Periodontal Res 30:73–79CrossRefGoogle Scholar
  23. 23.
    Khabbaz MG, Protogerou E, Douka E (2010) Radiographic quality of root fillings performed by undergraduate students. Int Endod J 43:499–508. CrossRefGoogle Scholar
  24. 24.
    Yoo YJ, Shon WJ, Baek SH, Kang MK, Kim HC, Lee W (2014) Effect of 1440-nanometer neodymium:yttrium-aluminum-garnet laser irradiation on pain and neuropeptide reduction: a randomized prospective clinical trial. J Endod 40:28–32. CrossRefGoogle Scholar
  25. 25.
    Shin SJ, Lee W, Lee JI et al (2011) Matrix metalloproteinase-8 and substance P levels in gingival crevicular fluid during endodontic treatment of painful, nonvital teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112:548–554. CrossRefGoogle Scholar
  26. 26.
    Awawdeh LA, Lundy FT, Linden GJ, Shaw C, Kennedy JG, Lamey PJ (2002) Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in gingival crevicular fluid associated with painful human teeth. Eur J Oral Sci 110:185–191CrossRefGoogle Scholar
  27. 27.
    Caviedes-Bucheli J, Muñoz HR, Azuero-Holguín MM, Ulate E (2008) Neuropeptides in dental pulp: the silent protagonists. J Endod 34:773–788CrossRefGoogle Scholar
  28. 28.
    Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86:1309–1379CrossRefGoogle Scholar
  29. 29.
    Schmelz M, Petersen LJ (2001) Neurogenic inflammation in human and rodent skin. Physiology 16:33–37CrossRefGoogle Scholar
  30. 30.
    Steinhoff M, Ständer S, Seeliger S, Ansel JC, Schmelz M, Luger T (2003) Modern aspects of cutaneous neurogenic inflammation. Arch Dermatol 139:1479–1488CrossRefGoogle Scholar
  31. 31.
    Theoharides TC, Singh KL, Boucher W et al (1998) Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects 1. Endocrinology 139:403–413CrossRefGoogle Scholar
  32. 32.
    Hong HS, Lee J, Lee E et al (2009) A new role of substance P as an injury-inducible messenger for mobilization of CD29+ stromal-like cells. Nat Med 15:425–435CrossRefGoogle Scholar
  33. 33.
    Pamuk F, Lutfioglu M, Aydogdu A, Koyuncuoglu CZ, Cifcibasi E, Badur OS (2017) The effect of low-level laser therapy as an adjunct to non-surgical periodontal treatment on gingival crevicular fluid levels of transforming growth factor-beta 1, tissue plasminogen activator and plasminogen activator inhibitor 1 in smoking and non-smoking chronic periodontitis patients: a split-mouth, randomized control study. J Periodontal Res 52:872–882. CrossRefGoogle Scholar
  34. 34.
    Kumaresan D, Balasundaram A, Naik VK, Appukuttan DP (2016) Gingival crevicular fluid periostin levels in chronic periodontitis patients following nonsurgical periodontal treatment with low-level laser therapy. Eur J Dent 10:546–550. CrossRefGoogle Scholar
  35. 35.
    Hochman B, Pinfildi CE, Nishioka MA et al (2014) Low-level laser therapy and light-emitting diode effects in the secretion of neuropeptides SP and CGRP in rat skin. Lasers Med Sci 29:1203–1208. CrossRefGoogle Scholar
  36. 36.
    Hsieh YL, Hong CZ, Chou LW, Yang SA, Yang CC (2015) Fluence-dependent effects of low-level laser therapy in myofascial trigger spots on modulation of biochemicals associated with pain in a rabbit model. Lasers Med Sci 30:209–216. CrossRefGoogle Scholar
  37. 37.
    Caviedes-Bucheli J, Moreno JO, Carreno CP et al (2013) The effect of single-file reciprocating systems on substance P and calcitonin gene-related peptide expression in human periodontal ligament. Int Endod J 46:419–426. CrossRefGoogle Scholar
  38. 38.
    Seltzer S, Bender IB (1984) The dental pulp: biologic considerations in dental procedures, 3rd edn. Lippincott Williams & Wilkins, Philadelphia PagesGoogle Scholar
  39. 39.
    Ghazi AM, Shuttleworth S, Angulo SJ, Pashley DH (2000) Gallium diffusion in human root dentin: quantitative measurements by pulsed Nd:YAG laser ablation combined with an inductively coupled plasma mass spectrometer. J Clin Laser Med Surg 18:173–183. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Endodontics, Faculty of DentistryKırıkkale UniversityKırıkkaleTurkey
  2. 2.Department of Endodontics, Faculty of DentistryAtaturk UniversityErzurumTurkey
  3. 3.Department of Periodontology, Faculty of DentistrySaglık Bilimleri UniversityİstanbulTurkey
  4. 4.Department of Periodontology, Faculty of DentistryAtaturk UniversityErzurumTurkey
  5. 5.Department of Periodontology, Faculty of Dentistryİzmir Katip Çelebi UniversityİzmirTurkey

Personalised recommendations