Dysregulation of the descending pain system in temporomandibular disorders revealed by low-frequency sensory transcutaneous electrical nerve stimulation: a pupillometric study.

Claudia Sommer,Annalisa Monaco,Eleonora Ortu,Luca Mesin,Mario Giannoni,Davide Pietropaoli,Ruggero Cattaneo

doi:10.1371/journal.pone.0122826

Abstract

Using computerized pupillometry, our previous research established that the autonomic nervous system (ANS) is dysregulated in patients suffering from temporomandibular disorders (TMDs), suggesting a potential role for ANS dysfunction in pain modulation and the etiology of TMD. However, pain modulation hypotheses for TMD are still lacking. The periaqueductal gray (PAG) is involved in the descending modulation of defensive behavior and pain through μ, κ, and δ opioid receptors. Transcutaneous electrical nerve stimulation (TENS) has been extensively used for pain relief, as low-frequency stimulation can activate µ receptors. Our aim was to use pupillometry to evaluate the effect of low-frequency TENS stimulation of μ receptors on opioid descending pathways in TMD patients. In accordance with the Research Diagnostic Criteria for TMD, 18 females with myogenous TMD and 18 matched-controls were enrolled. All subjects underwent subsequent pupillometric evaluations under dark and light conditions before, soon after (end of stimulation) and long after (recovery period) sensorial TENS. The overall statistics derived from the darkness condition revealed no significant differences in pupil size between cases and controls; indeed, TENS stimulation significantly reduced pupil size in both groups. Controls, but not TMD patients, displayed significant differences in pupil size before compared with after TENS. Under light conditions, TMD patients presented a smaller pupil size compared with controls; the pupil size was reduced only in the controls. Pupil size differences were found before and during TENS and before and after TENS in the controls only. Pupillometry revealed that stimulating the descending opioid pathway with low-frequency sensory TENS of the fifth and seventh pairs of cranial nerves affects the peripheral target. The TMD patients exhibited a different pattern of response to TENS stimulation compared with the controls, suggesting that impaired modulation of the descending pain system may be involved in TMD.

Highlights

Recent literature has suggested that temporomandibular disorders (TMDs) patients may suffer from dysfunction in the brain network that supports sensory, pain, emotional, and cognitive processes [1,2,3,4,5,6,7,8]
After Transcutaneous electric nerve stimulation (TENS), the reduction of pupil size remained significant in the control group (7886.51 vs. 7427.11; p = 0.003) but not in the TMD group (7599.88 vs. 7490.61; p = 0.082) because of the return of pupil size to that prior to TENS
The unpaired t test did not reveal any significant difference in pupil size between the control and TMD groups before TENS (7886.51 vs. 7599.88; p = 0.24), during TENS (7434.33 vs. 7184.94; p = 0.11), or after TENS (7427.11 vs. 7490.61; p = 0.47)

Summary

Introduction

Recent literature has suggested that TMD patients may suffer from dysfunction in the brain network that supports sensory, pain, emotional, and cognitive processes [1,2,3,4,5,6,7,8]. Among the structures that are involved in the brain network regulating the sensory, pain, emotional, and cognitive systems, the periaqueductal gray (PAG) has a key role. It receives afferent connections from cortical areas associated with cognition and motivation related to sensory and pain perception [15,16,17], and it projects the connections to the centers controlling the peripheral afferent inputs and couples autonomic reactions in a specific manner [18,19]. Low-frequency TENS is suggested to activate μ opioid receptors [30,31,32]

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