Background & Aims

Exploring cutaneous secondary hyperalgesia through experimental models provides valuable insights into the central mechanisms of pain, particularly those involving heterosynaptic facilitation. In addition, the degree of neuronal facilitation due to the secondary hyperalgesia could also be assessed with the aid of the nociceptive blink reflex (nBR), which has been consistently applied to evaluate the excitability of the trigeminal nociceptive pathways. This study aimed to investigate the effects of capsaicin-induced sensitization on these pathways, employing psychophysical and nBR assessment.

Methods

Twenty-eight healthy participants [mean age (SD) of 24.(3.6) years, 19 women and 9 men] underwent a 30-minute application of 1% capsaicin cream to the skin overlying the middle portion of the right masseter. Pain intensity during capsaicin application was measured using a 0-10 numerical rating scale every 5 minutes. The following outcomes were assessed before (baseline) and after capsaicin application at the entry zone of the infraorbital nerve on both ipsilateral and contralateral sides: psychophysical parameters, amplitude, and habituation of the R2 responses of the nBR, and the mechanical pain threshold (MPT). Repeated-measures ANOVA was applied to the data (p<0.050).

Results

The mean (SD) pain intensity during capsaicin application was 2.9 (2.0). The mean (SD) of the MPT of the ipsilateral side before and following capsaicin application was, respectively, 58.2 (74) and 64 (103) mN, with no differences (p>0.050). Likewise, the mean (SD) of the MPT of the contralateral side before and following capsaicin application was, respectively, 64 (93) and 64 (91) mN, with no differences (p>0.050). For nBR psychophysical parameters, the pain threshold to electrical stimulation on the ipsilateral side increased significantly after capsaicin application (1.1 [0.5] mA) compared to baseline (0.8 [0.3] mA; Tukey: p<0.001). Similarly, the contralateral side exhibited an increase in pain threshold (1.1 [0.7] mA vs. 0.9 [0.4] mA; Tukey: p=0.004). No significant effects of capsaicin were observed for the amplitude and habituation of the nBR R2 responses at a stimulation intensity of 2 times the pain threshold (p>0.050).

Conclusions

The absence of a significant decrease in MPT, coupled with a notable increase in pain threshold to electrical stimulation, suggests that endogenous pain inhibition may outweigh capsaicin-induced central sensitization in trigeminal nociceptive pathways. This nuanced interplay underscores the complexity of pain modulation mechanisms in response to capsaicin-induced sensitization.

References

Baad-Hansen, L., List, T., Jensen, T. S., Leijon, G. & Svensson, P. (2005). Blink reflexes in patients with atypical odontalgia. Journal of orofacial pain, 19, 239-247.
Baad-Hansen, L., List, T., Kaube, H., Jensen, T. S. & Svensson, P. (2006). Blink reflexes in patients with atypical odontalgia and matched healthy controls. Experimental brain research, 172, 498-506.
Costa, Y. M., Karlsson, P., Bonjardim, L. R., et al. (2019). Trigeminal nociceptive function and oral somatosensory functional and structural assessment in patients with diabetic peripheral neuropathy. Sci Rep, 9, 169.
Magerl, W., Fuchs, P. N., Meyer, R. A. & Treede, R. D. (2001). Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia. Brain : a journal of neurology, 124, 1754-1764.
Peddireddy, A., Wang, K., Svensson, P. & Arendt-Nielsen, L. (2009). Blink reflexes in chronic tension-type headache patients and healthy controls. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 120, 1711-1716.
Pillai, R. S., Pigg, M., List, T., et al. (2020). Assessment of Somatosensory and Psychosocial Function of Patients With Trigeminal Nerve Damage. Clin J Pain, 36, 321-335.
Treede, R. D. (2016). Gain control mechanisms in the nociceptive system. Pain, 157, 1199-1204.

Presenting Author

Yuri Costa

Poster Authors

Yuri M. Costa. DDS, Ph.D

University of Campinas

Lead Author

Peter Svensson

DDS

Department of Dentistry and Oral Health, Aarhus University

Lead Author

Fernando Exposto

Section of Orofacial Pain and Jaw Function, Aarhus University

Lead Author

Leonardo Bonjardim

University of São Paulo

Lead Author

Noeli Boscato

School of Dentistry, Federal University of Pelotas

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Orofacial Pain