A Human Model of Intraoral Pain and Heat Hyperalgesia

Aim: To examine, in a double-blind and placebo-controlled crossover manner, the effect of topical application of capsaicin on the alveolar mucosa with a battery of intraoral quantitative sen-sory testings (QST) in 16 healthy volunteers. Methods: Thirty µL of 5 mg/mL capsaicin or vehicle (control) was applied to a 3 × 3-mm paper disk and applied to the alveolar mucosa under an oral bandage. The subjects rated the perceived pain intensity on a 0 to 10 electronic visual analog scale (VAS) for 15 minutes. Quanti-tative sensory testings were performed before and immediately after the 15-minute application and consisted of assessments of cold detection threshold, warmth detection threshold (WDT), cold pain threshold, heat pain threshold (HPT), mechanical sensitivity to single and repeated punctate mechanical stimulation with von Frey filaments and to single and repeated brush stimulation with a cotton swab, and detection and pain thresholds to electrical stimulation of the alveolar mucosa and maxillary first premolar tooth. Analysis of variance was used to test the data. Results: Application of capsaicin caused moderate levels of pain (VASpeak scores 5.0 ± 1.9) whereas the vehicle was practically painless (VASpeak 0.9 ± 2.4). No significant effects of vehicle on QST could be detected (P ＞ .143). In contrast, capsaicin application was associated with significant decreases in WDT and HPT (P ＜ .001). No other significant changes in QST were observed for cap-saicin application. Conclusion: The intraoral capsaicin pain model is associated with signs of heat hyperalgesia, but not mechanical hyperalgesia. Since the somatosensory sensitivity is not well char-acterized in most orofacial pain conditions, mainly due to lack of tradition and techniques, intraoral QST may provide a better description of the somatosensory sensitivity and underlying mech-anisms in orofacial pain conditions.

capsaicin; hyperalgesia; orofacial pain; pain measurement

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;124:115–121.

2. Riley JL III, Gilbert GH, Heft MW. Orofacial pain symp-tom prevalence: Selective sex differences in the elderly?Pain 1998;76:97–104.

3. Marbach JJ. Is phantom tooth pain a deafferentation (neuropathic) syndrome? Part I: Evidence derived from patho-physiology and treatment. Oral Surg Oral Med Oral Pathol 1993;75:95–105.

4. Fricton JR. Atypical orofacial pain disorders: A study of diagnostic subtypes. Curr Rev Pain 2000;4:142–147.

5. Forssell H, Jääskeläinen S, Tenovuo O, Hinkka S. Sensory dysfunction in burning mouth syndrome. Pain 2002;99: 41–47.

6. Woda A, Pionchon P. A unified concept of idiopathic oro-facial pain: Clinical features. J Orofac Pain 1999;13: 172–184.

7. Woda A, Pionchon P. A unified concept of idiopathic orofacial pain: Pathophysiologic features. J Orofac Pain 2000; 14:196–212.

8. Jensen TS, Gottrup H, Sindrup SH, Bach FW. The clinical picture of neuropathic pain. Eur J Pharmacol 2001;429: 1–11.

9. Dyck PJ, Karnes JL, O’Brien PC, Zimmerman IR. Detection thresholds of cutaneous sensation in humans. In: Dyck PJ, Thomas PK, Griffin J, Low PA, Poduslo JF (eds). Peripheral Neuropathy, ed 3. Philadelphia: WB Saunders, 1993:706–728.

10. Lindblom U. Analysis of abnormal touch, pain, and tem-perature sensations in patients. In: Boivie J, Hansson P, Lindblom U (eds). Touch, Temperature, and Pain in Health and Disease: Mechanisms and Assessments. Seattle: IASP Press, 1994:63–84.

11. Grushka M, Sessle BJ, Howley TP. Psychophysical assessment of tactile, pain and thermal sensory functions in burning mouth syndrome. Pain 1987;28:169–184.

12. Svensson P, Bjerring P, Arendt-Nielsen L, Kaaber S. Quantitative determinations of sensory and pain thresholds on human oral mucosa by argon laser stimulation. Pain 1992;49:233–239.

13. Ngom PI, Dubray C, Woda A, Dallel R. A human oral capsaicin pain model to assess topical anesthetic-analgesic drugs. Neurosci Lett 2001;316:149–152.

14. Baumann TK, Simone DA, Shain CN, LaMotte RH. Neurogenic hyperalgesia: The search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia. J Neurophysiol 1991;66:212–227.

15. Koltzenburg M, Lundberg LER, Torebjörk HE. Dynamic and static components of mechanical hyperalgesia in human hairy skin. Pain 1992;51:207–219.

16. Kilo S, Schmelz M, Koltzenburg M, Handwerker HO. Different patterns of hyperalgesia induced by experimental inflammation in human skin. Brain 1994;117:385–396.

17. Andersen OK, Yucel A, Arendt-Nielsen L. Human models of hyperalgesia induced by capsaicin: A discussion of secondary hyperalgesia to heat. In: Harden RN, Baron R, Jänig W (eds). Complex Regional Pain Syndrome. Seattle: IASP Press, 2001:165–181.

18. Witting N, Svensson P, Gottrup H, Arendt-Nielsen L, Jensen TS. Intramuscular and intradermal injection of capsaicin: A comparison of local and referred pain. Pain 2000;84:407–412.

19. Svensson P, Petersen JK. Anesthetic effect of EMLA occluded with Orahesive oral bandages on oral mucosa. A placebo-controlled study. Anesth Prog 1992;39:79–82.

20. Svensson P, Graven-Nielsen T, Arendt-Nielsen L. Mechanical hyperesthesia of human facial skin induced by tonic painful stimulation of jaw muscles. Pain 1998;74: 93–100.

21. Arendt-Nielsen L, Brennum J, Sindrup S, Bak P. Electro-physiological and psychophysical quantification of temporal summation in the human nociceptive system. Eur J Appl Physiol 1994;68:266–273.

22. Green BG. Capsaicin desensitization and stimulus-induced recovery on facial compared to lingual skin. Physiol Behav 1998;65:517–523.

23. Fields HL. Pain: An unpleasant topic. Pain 1999;(Suppl 6):61–69.

24. Cliff MA, Green BG. Sensitization and desensitization to capsaicin and menthol in the oral cavity: Interactions and individual differences. Physiol Behav 1996;59:487–494.

25. Cliff MA, Green BG. Sensory irritation and coolness produced by menthol: Evidence for selective desensitisation of irritation. Physiol Behav 1994;56:1021–1029.

26. Petersen KL, Rowbotham MC. A new human experimental pain model: The heat/capsaicin sensitization model. NeuroReport 1999;10:1511–1516.

27. Romaniello A, Cruccu G, McMillan A, Arendt-Nielsen L, Svensson P. Effect of experimental pain from trigeminal muscle and skin on motor cortex excitability in humans. Brain Res 2000;882:120–127.

28. Svensson P, Arendt-Nielsen L, Bjerring P. Response of BMS patients to long duration nociceptive heat, cold pressor and capsaicin stimuli [abstract]. J Orofac Pain 1993;7:115.

29. Morris VH, Cruwys SC, Kidd BL. Characterization of capsaicin-induced mechanical hyperalgesia as a marker for altered nociceptive processing in patients with rheumatoid arthritis. Pain 1997;71:179–186.

30. Petersen KL, Fields HL, Brennum J, Sandroni P, Row-botham MC. Capsaicin evoked pain and allodynia in post-herpetic neuralgia. Pain 2000;88:125–133.

31. Sessle BJ. The neurobiology of facial and dental pain: pre-sent knowledge, future directions. J Dent Res 1987;66: 962–981.

32. Caterina MJ, Schumacher MA, Tominaga M. The cap-saicin receptor: A heat-activated ion channel in the pain pathway. Nature 1997;389:816–824.

33. Simone DA, Baumann TK, LaMotte RH. Dose-dependent pain and mechanical hyperalgesia in humans after intradermal injection of capsaicin. Pain 1989;38:99–107.

34. Green BG. Rapid recovery from capsaicin desensitization during recurrent stimulation. Pain 1996;68:245–253.

35. Ren K, Dubner R. Central nervous system plasticity and persistent pain. J Orofac Pain 1999;13:155–163.