Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action.

Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, non-pharmacologic treatment for patients with intractable chronic pain conditions. Chronic pain is a widely heterogenous syndrome with regard to both pathophysiology and the resultant phenotype. Despite advances in our understanding of SCS-mediated antinociception, there still exists limited evidence clarifying the pathways recruited when patterned electric pulses are applied to the epidural space. The rapid clinical implementation of novel SCS methods including burst, high frequency and dorsal root ganglion SCS has provided the clinician with multiple options to treat refractory chronic pain. While compelling evidence for safety and efficacy exists in support of these novel paradigms, our understanding of their mechanisms of action (MOA) dramatically lags behind clinical data. In this review, we reconstruct the available basic science and clinical literature that offers support for mechanisms of both paresthesia spinal cord stimulation (P-SCS) and paresthesia-free spinal cord stimulation (PF-SCS). While P-SCS has been heavily examined since its inception, PF-SCS paradigms have recently been clinically approved with the support of limited preclinical research. Thus, wide knowledge gaps exist between their clinical efficacy and MOA. To close this gap, many rich investigative avenues for both P-SCS and PF-SCS are underway, which will further open the door for paradigm optimization, adjunctive therapies and new indications for SCS. As our understanding of these mechanisms evolves, clinicians will be empowered with the possibility of improving patient care using SCS to selectively target specific pathophysiological processes in chronic pain

Toward Composite Pain Biomarkers of Neuropathic Pain—Focus on Peripheral Neuropathic Pain

Chronic pain affects ~10–20% of the U.S. population with an estimated annual cost of $600 billion, the most significant economic cost of any disease to-date. Neuropathic pain is a type of chronic pain that is particularly difficult to manage and leads to significant disability and poor quality of life. Pain biomarkers offer the possibility to develop objective pain-related indicators that may help diagnose, treat, and improve the understanding of neuropathic pain pathophysiology. We review neuropathic pain mechanisms related to opiates, inflammation, and endocannabinoids with the objective of identifying composite biomarkers of neuropathic pain. In the literature, pain biomarkers typically are divided into physiological non-imaging pain biomarkers and brain imaging pain biomarkers. We review both types of biomarker types with the goal of identifying composite pain biomarkers that may improve recognition and treatment of neuropathic pain

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

IntroductionSpinal 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.MethodsA retrospective cohort study of SCS patients implanted between 2004 and 2020 (n = 237) was conducted. Descriptive statistics and linear mixed methods analyses were used.ResultsHF-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.DiscussionPPR 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

A high-frequency mobile phone data collection approach for research in social-environmental systems: Applications in climate variability and food security in sub-Saharan Africa

Collecting high-frequency social-environmental data about farming practices in sub-Saharan Africa can provide new insight into environmental changes that farmers face and how they respond within smallholder agro-eco-systems. Traditional data collection methods such as agricultural censuses are costly and not useful for understanding intra-annual and real-time decisions. Short-message service (SMS) has the potential to transform the nature of data collection in coupled social-ecological systems. We present a system for collecting, managing, and synthesizing weekly data from farmers, including data infrastructure for management of big and heterogeneous datasets; probabilistic data quality assessment tools; and visualization and analysis tools such as mapping and regression techniques. We discuss limitations of collecting social-environmental data via SMS and data integration challenges that arise when linking these data with other social and environmental data. In combination with high-frequency environmental data, such data will help ameliorate issues of scale mismatch and build resilience in environmental systems.National Science Foundation [SES-1360463, SES-1534544, BCS-1115009]; NASA New Investigator Program [NNX15AC64G]24 month embargo; published online: 20 May 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Toward Composite Pain Biomarkers of Neuropathic Pain-Focus on Peripheral Neuropathic Pain.

Chronic pain affects ~10-20% of the U.S. population with an estimated annual cost of $600 billion, the most significant economic cost of any disease to-date. Neuropathic pain is a type of chronic pain that is particularly difficult to manage and leads to significant disability and poor quality of life. Pain biomarkers offer the possibility to develop objective pain-related indicators that may help diagnose, treat, and improve the understanding of neuropathic pain pathophysiology. We review neuropathic pain mechanisms related to opiates, inflammation, and endocannabinoids with the objective of identifying composite biomarkers of neuropathic pain. In the literature, pain biomarkers typically are divided into physiological non-imaging pain biomarkers and brain imaging pain biomarkers. We review both types of biomarker types with the goal of identifying composite pain biomarkers that may improve recognition and treatment of neuropathic pain

Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action.

Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, non-pharmacologic treatment for patients with intractable chronic pain conditions. Chronic pain is a widely heterogenous syndrome with regard to both pathophysiology and the resultant phenotype. Despite advances in our understanding of SCS-mediated antinociception, there still exists limited evidence clarifying the pathways recruited when patterned electric pulses are applied to the epidural space. The rapid clinical implementation of novel SCS methods including burst, high frequency and dorsal root ganglion SCS has provided the clinician with multiple options to treat refractory chronic pain. While compelling evidence for safety and efficacy exists in support of these novel paradigms, our understanding of their mechanisms of action (MOA) dramatically lags behind clinical data. In this review, we reconstruct the available basic science and clinical literature that offers support for mechanisms of both paresthesia spinal cord stimulation (P-SCS) and paresthesia-free spinal cord stimulation (PF-SCS). While P-SCS has been heavily examined since its inception, PF-SCS paradigms have recently been clinically approved with the support of limited preclinical research. Thus, wide knowledge gaps exist between their clinical efficacy and MOA. To close this gap, many rich investigative avenues for both P-SCS and PF-SCS are underway, which will further open the door for paradigm optimization, adjunctive therapies and new indications for SCS. As our understanding of these mechanisms evolves, clinicians will be empowered with the possibility of improving patient care using SCS to selectively target specific pathophysiological processes in chronic pain

Whole-Body Vibration Prevents Neuronal, Neurochemical, and Behavioral Effects of Morphine Withdrawal in a Rat Model

Peripheral mechanoreceptor-based treatments such as acupuncture and chiropractic manipulation have shown success in modulating the mesolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) of the midbrain and projecting to the nucleus accumbens (NAc) of the striatum. We have previously shown that mechanoreceptor activation via whole-body vibration (WBV) ameliorates neuronal and behavioral effects of chronic ethanol exposure. In this study, we employ a similar paradigm to assess the efficacy of WBV as a preventative measure of neuronal and behavioral effects of morphine withdrawal in a Wistar rat model. We demonstrate that concurrent administration of WBV at 80 Hz with morphine over a 5-day period significantly reduced adaptations in VTA GABA neuronal activity and NAc DA release and modulated expression of δ-opioid receptors (DORs) on NAc cholinergic interneurons (CINs) during withdrawal. We also observed a reduction in behavior typically associated with opioid withdrawal. WBV represents a promising adjunct to current intervention for opioid use disorder (OUD) and should be examined translationally in humans