Nerve Growth Factor and Sensory Neuropeptide Levels in Plasma and Saliva of Various Orofacial Pain Patients

다양한 구강안면통증환자의 혈장 및 타액에서의 신경성장인자와 감각성 신경펩티드 농도에 관한 연구

  • Jang, Min-Uk (Department of Oral Medicine and Oral Diagnosis School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Chung, Sung-Chang (Department of Oral Medicine and Oral Diagnosis School of Dentistry and Dental Research Institute, Seoul National University) ;
  • Chung, Jin-Woo (Department of Oral Medicine and Oral Diagnosis School of Dentistry and Dental Research Institute, Seoul National University)
  • 장민욱 (서울대학교 치의학대학원 구강내과진단학교실, 치학연구소) ;
  • 정성창 (서울대학교 치의학대학원 구강내과진단학교실, 치학연구소) ;
  • 정진우 (서울대학교 치의학대학원 구강내과진단학교실, 치학연구소)
  • Published : 2009.12.30


Nerve growth factor (NGF) and sensory neuropeptides are involved in the process of nociception at peripheral nerve fibers and wide spread in central nervous system. The aims of this study were to investigate NGF and sensory neuropeptides (substance P [SP] and calcitonin gene-related peptide [CGRP]) levels in human plasma and saliva, and the associations between these sensory neuropeptides levels and chronic orofacial pain symptoms. NGF, SP, and CGRP levels in plasma and resting whole saliva samples collected from 67 orofacial pain patients (joint pain, dental or periodontal pain, mucosal pain) and 36 pain free control subjects were measured by enzyme immunoassay. The characteristic pain intensity of each subject was measured using the Graded Chronic Pain Scale and the flow rate of resting whole saliva was measured. Joint pain patients group showed significantly higher plasma NGF level compared to each of dental pain patients (p<0.01), mucosal pain patients (p<0.01), and control group (p<0.01). Plasma NGF level of dental pain patients group was significantly higher than that of control group (p<0.01). Saliva SP level of dental pain patients group (p<0.05) and saliva CGRP level of mucosal pain group (p<0.05) were significantly higher than that of control group. Plasma and saliva SP levels of joint pain patients was significantly associated with pain intensity (plasma: standardized coefficient=0.599, p<0.01, saliva: standardized coefficient=0.504, p=0.05). In dental pain patients group, plasma SP (standardized coefficient=0.559, p<0.01), saliva SP (standardized coefficient=0.520, p<0.01) and saliva CGRP (standardized coefficient=0.599, p<0.01) levels were significantly associated with age. In mucosal pain patients group, plasma SP (standardized coefficient=0.495, p<0.05), saliva SP (standardized coefficient=0.500, p<0.05), and saliva CGRP (standardized coefficient=0.717, p<0.01) levels were significantly associated with age. NGF and neuropeptides may play a role in the maintenance of various orofacial pain symptoms. The examination of those levels in plasma and saliva helps understanding the mechanism of orofacial pain, and furthermore, can be applied to the diagnosis and therapy of orofacial pain.


  1. Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc 1993;124(10):115-21
  2. Russell IJ, Orr MD, Littman B, Vipraio GA, Alboukrek D, Michalek JE, Lopez Y, MacKillip F. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994 Nov;37(11):1593-601
  3. Marukawa H, Shimomura T, Tahahashi K. Salivary substance P, 5- ydroxytryptamin, and gammaaminobutyric acid levels in migraine and tension-type headache. Headache 1996 Frb;36(2):100-104
  4. Nicolodi M, Del Bianco E. Sensory neuropeptides (substance P, calcitonin gene-related peptide) and vasoactive intestinal polypeptide in human saliva:their pattern in migraine and cluster headache. Cephalalgia 1990;10;39-50
  5. Donnerer J, Schuligoi R, Stein C. Increased content and transport of substance P and calcitonin-gene related peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory function of nerve growth factor in vivo. Neuroscience 1992;49:693-698
  6. Woolf CJ, Safieh-Garabedian B, Ma Q-P, Crilly P, Winter J. Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. Neuroscience 1994;62(2);327-331
  7. Cirulli F. Role of environmental factors on brain development and nerve growth factor expression. Physiol Behav. 2001 Jun;73:321-330. Review
  8. Hadjiconstantinou M, McGuire L, Duchemin AM, Laskowski B, Kiecolt-Glaser J, Glaser R. Changes in plasma nerve growth factor levels in older adults associated with chronic stress. J Neuroimmunol 2001 May1;116(1):102-106
  9. Von Korff M, Ormel J, Keefe FJ, Dworkin SF. Grading the severity of chronic pain. Pain 1992;50:133-49
  10. Shu X-Q, Mendell LM. Neurotrophins and hyperalgesia. Proc Natl Acad Sci USA 1999;96:7693-7696
  11. Kolzenburg M, Bennett DL, Shelton DL. Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin. Eur J Neurosci 1999;11:1698-1704
  12. Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA. Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci 2002;22(20):9086-9098
  13. Aloe L, Tuveri MA, Carcassi U, Levi-Montalcini R. Nerve growth factor in the synovial fluid of patients with chronic arthritis. Arthritis and Rheumatism 1992;35(3):351-355
  14. Dicou E, Perrot S, Menkes CJ, Masson C, Nerriere V. Nerve growth factor(NGF) autoantibodies and NGF in the synovial fluid: implications in spondylarthropathies. Autoimmunity 1996 24(1):1-9
  15. Pelegrini-da-Silva A, Oliviera MCG, Parada CA, Tambeli CH. Nerve growth factor acts with the 2-adrenoceptor to induce spontaneous nociceptive behavior during tempromandibular joint inflammatory hyperalgesia. Life Science 2008;83:780-785
  16. Paola S, Andrea A, Ardesio F, Virgilio G. Levels of nerve growth factor in cerebrospinal fluid of chronic daily headache patients. Neurology 2001;57:132-134