Sex-specific differences in the efficacy of traditional low frequency versus high frequency spinal cord stimulation for chronic pain

Rosalynn R Z Conic; Jacob Caylor; Christina L Cui; Zabrina Reyes; Eric Nelson; Sopyda Yin; Imanuel Lerman

doi:10.1186/s42234-022-00090-2

Sex-specific differences in the efficacy of traditional low frequency versus high frequency spinal cord stimulation for chronic pain

Bioelectron Med. 2022 Apr 28;8(1):8. doi: 10.1186/s42234-022-00090-2.

Authors

Rosalynn R Z Conic^{1

2}, Jacob Caylor^{2

3}, Christina L Cui⁴, Zabrina Reyes⁵, Eric Nelson⁶, Sopyda Yin², Imanuel Lerman^{7

8

9

10}

Affiliations

¹ Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA.
² Department of Anesthesiology, Center for Pain Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.
³ Northwest Pain Care, PS, Spokane, WA, USA.
⁴ Division of Vascular and Endovascular Surgery, Department of Surgery, Duke University Medical Center, Durham, NC, USA.
⁵ School of Medicine, University of California, San Diego, San Diego, CA, USA.
⁶ College of Osteopathic Medicine of the Pacific Western University of Health Sciences, Pomona, CA, USA.
⁷ Department of Anesthesiology, Center for Pain Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA. ilerman@ucsd.edu.
⁸ Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, USA. ilerman@ucsd.edu.
⁹ VA Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA, USA. ilerman@ucsd.edu.
¹⁰ Affiliate Electrical and Computer Engineering, VA San Diego Healthcare System, Center for Stress and Mental Health, Center for Pain Medicine, UC San Diego Health, Qualcomm Institute, California Institute for Telecommunications and Information Technology (Calit2), VA San Diego, 3350 La Jolla Village Dr, (MC116A), San Diego, CA, 92161, USA. ilerman@ucsd.edu.

Abstract

Introduction: Spinal cord stimulation (SCS), an FDA-approved therapy for chronic pain, uses paresthesia (low frequency SCS (LF-SCS)) or paresthesia-free (such as high-frequency SCS (HF-SCS)) systems, providing analgesia through partially-elucidated mechanisms, with recent studies indicating a sexual dimorphism in pain pathogenesis (Bretherton et al., Neuromodulation, 2021; Paller et al., Pain Med 10:289-299, 2009; Slyer et al., Neuromodulation, 2019; Van Buyten et al., Neuromodulation 20:642-649, 2017; Mekhail et al., Pain Pract, 2021). We aim to evaluate SCS therapy sex effects based on paradigm, utilizing visual analog scores (VAS), perceived pain reduction (PPR), and opioid use.

Methods: A retrospective cohort study of SCS patients implanted between 2004 and 2020 (n = 237) was conducted. Descriptive statistics and linear mixed methods analyses were used.

Results: HF-SCS (10 kHz) was implanted in 94 patients (40 females, 54 males), and LF-SCS in 143 (70 females, 73 males). At 3 months and 6 months, HF-SCS (p < 0.001) and LF-SCS (p < 0.005) had lower VAS scores compared to baseline (p < 0.005), with no differences across groups. PPR improved in both post-implantation (p < 0.006) and at 3 months (p < 0.004 respectively), compared to baseline persisting to 6 (p < 0.003) and 12 months (p < 0.01) for HF-SCS, with significantly better PPR for HF-SCS at 3 (p < 0.008) and 6 (p < 0.001) months compared to LF-SCS. There were no differences in opioid use from baseline for either modality; however LF-SCS patients used more opioids at every time point (p < 0.05) compared to HF-SCS. VAS was improved for all modalities in both sexes at 3 months (p = 0.001), which persisted to 6 months (p < 0.05) for HF-SCS males and females, and LF-SCS females. Female HF-SCS had improved PPR at 3 (p = 0.016) and 6 (p = 0.022) months compared to baseline, and at 6 (p = 0.004) months compared to LF-SCS. Male HF-SCS and LF-SCS had improved PPR post-implantation (p < 0.05) and at 3 months (p < 0.05), with HF-SCS having greater benefit at 3 (p < 0.05) and 6 (p < 0.05) months. LF-SCS males but not females used less opioids at 6 months (p = 0.017) compared to baseline; however this effect did not persist. On linear mixed model analyses, including age, sex and stimulator type, VAS decreased with age, at each timepoint, and had a trend towards increasing with female sex, while PPR increased at 3 and 6 months and lastly HF-SCS was associated with decreased opioid use.

Discussion: PPR at 3 and 6 months improved to a greater extent in HF-SCS. HF-SCS females had improved PPR at 3 and 6 months, and only LF-SCS males used less opioids at 6 months, potentially indicating sex-based pathway. Future studies should further elucidate differences in sex-based pathways and identify optimal SCS opioid-sparing paradigms for chronic pain patients.

Keywords: HF-SCS; LF-SCS; Opioid; Outcomes; Sex; Spinal cord stimulator; VAS.

Abstract

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