INTRODUCTION

Labor pain includes a chain of physiological processes, such as uterine contractions, cervical dilation, fetal descent, perineal stretching to descent, and the birth of the baby [1]. Although pain accompanies during labor, the perception of each individual’s response to the labor pain is highly variable, leading to noticeable changes in the brain pain network. The origin of brain pain network changes during labor is still an unanswered question. Labor pain relief becomes a priority campaign to reduce pain perception, which also eliminates the negative impact on the cognitive system and brain connectivity. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive nonpharmacological intervention for pain relief during labor [2; 3; 4]. Azar et al. concluded that TENS could reduce labor pain without any unexpected side effects [5]. However, evidence for how TENS affects brain networks should be further determined by imaging-related studies. We hypothesized that TENS would significantly impact neural activities through its pain-relieving function. The exploring characteristics of both local and global pain networks in the brain were performed in the current study. Additionally, analyzing the network alternations correspond to the sensation of labor pain with and without applying TENS. The information will display on the brain activation maps and the functional neural network model.

METHODS

Twenty-two pregnant women at the active stage of laboring were recruited. Fifteen women (aged 29.0 ± 5.4 years old) were used TENS as the anesthesia approach and seven subjects (aged 29.6 ± 2.3 years old) were normal delivery without TENS. A portable battery-powered TENS unit (HANS model, LH202H, Singapore) was placed at bilateral Hegu (Li 4) and Sanyinjiao (Sp 6) [4] of the skin for the participant. TENS setting was as follows: output, 15 milliamperes; frequency, 100 Hz; burst frequency, 2 Hz; pulse duration, 0.25 ms, total time, 30 min. A TENS session for 30 min was applied when the parturient needed pain relief during the first stage of labor. Images were acquired from a 1.5 T MR scanner (Intera, Philips, Best, Holland). Functional MRI was acquired using a single-shot gradient-recalled echo-planar imaging (EPI) sequence with the following parameters: 28 slices; TR, 3000 ms; TE, 40 ms; voxel size, 3× 3×5 mm³; matrix size, 64×64; Scan time: 360 seconds. Five sessions in maximum were conducted according to the status of the participant. Function MRI data with an estimation of functional connectivity was analyzed by using DPABI (https://www.rfmri.org/dpabi). Images were parcellated into 246 regions of interest to explore the functional connectivity according to the BN246 atlas [6]. Each subject calculated the functional connectivity between ROIs, and Fisher's z-transformation was performed to normalize the correlation coefficients. Generalized estimating equations (GEE) were performed to reveal significant functional connectivity between two different ROIs with p <0.05 with the Bonferroni correction method (0.05/246).

RESULTS

Figure 1 represents the connections with significant differences between the control and TENS groups during labor. Functional connectivity was with a significant increase pattern in TENS than in the control group. The involved connections were between (1) left middle frontal gyrus and right nuclear accumbens; (2) left middle frontal gyrus and left precuneus; (3) right insula and right inferior frontal gyrus; (4) left postcentral gyrus and right inferior frontal gyrus; (5) left superior parietal lobule and right orbital gyrus; (6) left, right medial orbital gyrus and right superior temporal gyrus. Figure 2 represented the connections with significant differences between TENS groups with high and low pain scores. The most significant connection nodes between high and low pain scores involved the prefrontal cortex and orbital gyrus. Significant correlations were found between the reduction in NRS score and the functional connectivity. The involved connections were located between the right middle frontal gyrus and left superior temporal gyrus (Spearman’s rho = 0.835, p=0.00011), the right middle frontal gyrus and right cingulate gyrus (Spearman’s rho = 0.829, p=0.00013), the left postcentral gyrus and left thalamus (Spearman’s rho = 0.829, p=0.00014), right insula to left precuneus (Spearman’s rho = 0.829, p=0.00013), right occipital gyrus (Spearman’s rho = 0.831, p=0.00012), and left occipital gyrus (Spearman’s rho = 0.833, p=0.00012), and right inferior parietal lobule to left occipital gyrus (Spearman’s rho = 0.833, p=0.00012) (Figure 3).

DISCUSSION

During normal delivery with TENS, the cortical regions with functional connectivity change are located in the middle frontal gyrus, insula, postcentral (primary somatosensory cortex; S1), superior parietal lobule (S2). The result is consistent with the cortical regions involved in visceral and nociceptive pain [7]. The orbital gyrus, which was related to the processing of pain stimuli [8; 9], altered when connecting with the superior temporal gyrus. The anterior cingulate gyrus and inferior frontal gyrus were represented in the functional connectivity of participants with a low pain score group after TENS treatment, which all involved in the pain processing network [10; 11]. The cortical region related to sensory, affective, and modulatory activations about pain might differ in conditions of functional connectivity with and without TENS treatment.

CONCLUSION

We observed significant alternations in functional connectivity by TENS treatment from resting-state fMRI, which might provide a convincing motive for applying for nonpharmacological relief and developing alternative pain-management approaches.

Acknowledgements

The imaging facility was supported by the Molecular Imaging Center of Chang Gung Memorial Hospital, Linkou. The authors are grateful to the Neuroscience Research Center of Chang Gung Memorial Hospital, Linkou.

References

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