Spatial and Temporal Effects of Capsaicin and Menthol on Intraoral Somatosensory Sensitivity

Aims: To assess the spatial and temporal sensory effects of the topical application of capsaicin and menthol on the gingiva of healthy volunteers. Methods: Capsaicin, menthol, and saline (control) were applied topically on the gingiva in the maxillary premolar area of healthy volunteers for 15 minutes. Pain intensity was rated on a 0 to 10 visual analog scale (VAS). Before, immediately after, and 30 minutes after application, three mechanical stimuli were applied at 15 gingival sites: fixed-intensity stimuli were applied by 32 mN and 512 mN von Frey filaments, and stimuli of increasing intensity were applied by an electronic von Frey (EVF, 10 g/s). The EVF was used to test the pinprick pain threshold (PiPT). The perceived pain from filament stimulation was rated on a 0-50-100 numeric rating scale (NRS). Analysis of variance for repeated measures was used to analyze the NRS scores, PiPT values, the number of hypersensitive or hyposensitive test sites, and the coordinates of the center of gravity (COG) of somatosensory sensitivity. Results: The mean ± SEM VAS score of pain intensity produced by the application of capsaicin (4.6 ± 0.5) was significantly higher than that produced by menthol (0.3 ± 0.2) and saline (0.1 ± 0.1) (P < .001). Capsaicin induced local desensitization to all stimuli (P < .047) , and at the application site, capsaicin induced significant desensitization to 512 mN stimuli (P = .003). Menthol did not induce significant somatosensory changes (P > .147), and saline induced slight desensitization in two sites surrounding the application site (P < .023). The COG coordinates did not shift significantly over time during any condition (P > .125). Conclusion: Capsaicin but not menthol induced mechanical desensitization in the application area but not in the surrounding areas.

capsaicin; intraoral somatosensory testing; menthol; psychophysics; spatial; temporal

1. Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain 2006; 123:231–243.

2. Serra J, Campero M, Bostock H, Ochoa J. Two types of C nociceptors in human skin and their behavior in areas of capsaicin-induced secondary hyperalgesia. J Neurophysiol 2004;91: 2770–2781.

3. Xing H, Chen M, Ling J, Tan W, Gu JG. TRPM8 mechanism of cold allodynia after chronic nerve injury. J Neurosci 2007; 27:13680–13690.

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

5. Baad-Hansen L, Jensen TS, Svensson P. A human model of intraoral pain and heat hyperalgesia. J Orofac Pain 2003;17:333–340.

6. Hatem S, Attal N, Willer JC, Bouhassira D. Psychophysical study of the effects of topical application of menthol in healthy volunteers. Pain 2006;122:190–196.

7. Binder A, Stengel M, Klebe O, Wasner G, Baron R. Topical high-concentration (40%) menthol-somatosensory profile of a human surrogate pain model. J Pain 2011;12:764–773.

8. Namer B, Kleggetveit IP, Handwerker H, Schmelz M, Jorum E. Role of TRPM8 and TRPA1 for cold allodynia in patients withcold injury. Pain 2008;139:63–72.

9. Magerl W, Fuchs PN, Meyer RA, Treede RD. Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia. Brain 2001;124:1754–1764.

10. Magerl W, Treede RD. Secondary tactile hypoesthesia: A novel type of pain-induced somatosensory plasticity in human subjects. Neurosci Lett 2004;361:136–139.

11. LaMotte RH, Shain CN, Simone DA, Tsai EF. Neurogenic hyperalgesia: Psychophysical studies of underlying mechanisms. J Neurophysiol 1991;66:190–211.

12. Ziegler EA, Magerl W, Meyer RA, Treede RD. Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input. Brain 1999;122(Pt 12): 2245–2257.

13. Torebjork HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol 1992;448:765–780.

14. Lu SY, Baad-Hansen L, List T, Zhang ZT, Svensson P. Somatosensory profiling of intraoral capsaicin and menthol in healthy subjects. Eur J Oral Sci 2013;121:29–35.

15. Lu SY, Baad-Hansen L, Zhang ZT, Svensson P. Reliability of a new technique for intraoral mapping of somatosensory sensitivity. Somatosens Mot Res 2013;30:30–36.

16. Dworkin SF, LeResche L. Research diagnostic criteria for temporomandibular disorders: Review, criteria, examinations and specifications, critique. J Craniomandib Disord 1992;6: 301–355.

17. Baad-Hansen L, List T, Jensen TS, Svensson P. Increased pain sensitivity to intraoral capsaicin in patients with atypical odontalgia. J Orofac Pain 2006;20:107–114.

18. Svensson P, Baad-Hansen L, Pigg M, et al. Guidelines and recommendations for assessment of somatosensory function in orofacial pain conditions—A taskforce report. J Oral Rehabil 2011;38:366–394.

19. Rolke R, Magerl W, Campbell KA, et al. Quantitative sensory testing: A comprehensive protocol for clinical trials. Eur J Pain 2006;10:77–88.

20. Roberts K, Shenoy R, Anand P. A novel human volunteer pain model using contact heat evoked potentials (CHEP) following topical skin application of transient receptor potential agonists capsaicin, menthol and cinnamaldehyde. J Clin Neurosci 2011; 18:926–932.

21. Thygesen TH, Norholt SE, Jensen J, Svensson P. Spatial and temporal assessment of orofacial somatosensory sensitivity: A methodological study. J Orofac Pain 2007;21:19–28.

22. Ayesh EE, Ernberg M, Svensson P. Effects of local anesthetics on somatosensory function in the temporomandibular joint area. Exp Brain Res 2007;180:715–725.

23. 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.

24. Huang JH, Ali Z, Travison TG, Campbell JN, Meyer RA. Spatial mapping of the zone of secondary hyperalgesia reveals a gradual decline of pain with distance but sharp borders. Pain 2000; 86:33–42.

25. Ridding MC, Brouwer B, Miles TS, Pitcher JB, Thompson PD. Changes in muscle responses to stimulation of the motor cortex induced by peripheral nerve stimulation in human subjects. Exp Brain Res 2000;131:135–143.

26. Svensson P, Baad-Hansen L, Pigg M, et al. Guidelines and recommendations for assessment of somatosensory function in orofacial pain conditions – a taskforce report. J Oral Rehabil 2011;38:366–94.

27. 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.

28. Beydoun A, Dyke DB, Morrow TJ, Casey KL. Topical capsaicin selectively attenuates heat pain and A delta fiber-mediated laser-evoked potentials. Pain 1996;65:189–196.

29. Wasner G, Schattschneider J, Binder A, Baron R. Topical menthol—a human model for cold pain by activation and sensitization of C nociceptors. Brain 2004;127:1159–1171.

30. Peier AM, Moqrich A, Hergarden AC, et al. A TRP channel that senses cold stimuli and menthol. Cell 2002;108:705–715.