Lack of Analgesic Synergy of the Cholecystokinin Receptor Antagonist Proglumide and Spinal Cord Stimulation for the Treatment of Neuropathic Pain in Rats

Inoue, Shinsuke; Johanek, Lisa M.; Sluka, Kathleen A.

doi:10.1111/ner.12601

Cited by 7 publications

(5 citation statements)

References 96 publications

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“…Interestingly, administering the DOR antagonist naltrindole abolished analgesia induced by 60 Hz but not by 4 Hz SCS. Finally, a recent preclinical study simultaneously applied SCS and the cholecystokinin (CCK) receptor antagonist proglumide ( Inoue et al, 2017 ). While CCK receptor antagonists typically enhance opioid-dependent analgesia, co-application of SCS and proglumide did not provide enhanced analgesia compared to a single therapy alone.…”

Section: Neurostimulation Therapies For Chronic Painmentioning

confidence: 99%

The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia

Lubejko

Graham

Livrizzi

et al. 2022

Front. Syst. Neurosci.

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Due to the prevalence of chronic pain worldwide, there is an urgent need to improve pain management strategies. While opioid drugs have long been used to treat chronic pain, their use is severely limited by adverse effects and abuse liability. Neurostimulation techniques have emerged as a promising option for chronic pain that is refractory to other treatments. While different neurostimulation strategies have been applied to many neural structures implicated in pain processing, there is variability in efficacy between patients, underscoring the need to optimize neurostimulation techniques for use in pain management. This optimization requires a deeper understanding of the mechanisms underlying neurostimulation-induced pain relief. Here, we discuss the most commonly used neurostimulation techniques for treating chronic pain. We present evidence that neurostimulation-induced analgesia is in part driven by the release of endogenous opioids and that this endogenous opioid release is a common endpoint between different methods of neurostimulation. Finally, we introduce technological and clinical innovations that are being explored to optimize neurostimulation techniques for the treatment of pain, including multidisciplinary efforts between neuroscience research and clinical treatment that may refine the efficacy of neurostimulation based on its underlying mechanisms.

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Section: Neurostimulation Therapies For Chronic Painmentioning

confidence: 99%

The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia

Lubejko

Graham

Livrizzi

et al. 2022

Front. Syst. Neurosci.

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“…There is likely an analgesic ceiling effect in regard to opioidergic pathways recruited by P-SCS. In a rat SNI model treated with P-SCS, administration of the opioidergic enhancer proglumide had no additive or synergistic effect on PWT or physical activity levels (Inoue et al, 2017). Tolerance and time-limited opioidergic analgesia that contribute to the clinical efficacy of P-SCS may also apply to PF-SCS.…”

Section: Segmental and Supraspinal Neurotransmittersmentioning

confidence: 99%

“…Opioidergic mechanisms contribute to P-SCS-mediated analgesia with frequency-dependent, differential activation of opioid receptor subclasses (Sato et al, 2013). Moreover, there may be a development of tolerance to opioidergic recruitment as well as an opioidergic ceiling effect of maximal benefit, which should be further investigated (Chandran & Sluka, 2003; Inoue et al, 2017). The site of action and mechanism of P-SCS opioidergic recruitment remains to be determined.…”

Section: P-scs and Pf-scs Mechanisms: Evidence And Theorymentioning

confidence: 99%

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

et al. 2019

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Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, nonpharmacologic 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.

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“…A recent study using prolonged SCS at low (4 Hz) and typical (60 Hz) frequencies found differential modulation by opioid receptor subtype, such that μ opioid receptor blockade with naloxone prevented the SCS‐mediated analgesia at low frequencies, whereas δ opioid receptor blockade with naltrindole blocked effects of 60‐Hz stimulation . Interestingly, the same group published a study in which proglumide, a drug that enhances the analgesic properties of opioids, had no effect on SCS analgesia or physical activity levels in rats . Another group found that opioid antagonism with naloxone blocked early SCS (administered 3 days after nerve injury), but had no effect on late SCS …”

Section: Conventional Waveformsmentioning

confidence: 99%

“…113 Interestingly, the same group published a study in which proglumide, a drug that enhances the analgesic properties of opioids, had no effect on SCS analgesia or physical activity levels in rats. 114 Another group found that opioid antagonism with naloxone blocked early SCS (administered 3 days after nerve injury), but had no effect on late SCS. 115 SCS depresses the activity of wide dynamic range (WDR) neurons, a class of output neurons located in the deep dorsal horn lamina.…”

Section: Burstmentioning

confidence: 99%

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms

2018

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Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy.

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Lack of Analgesic Synergy of the Cholecystokinin Receptor Antagonist Proglumide and Spinal Cord Stimulation for the Treatment of Neuropathic Pain in Rats

Cited by 7 publications

References 96 publications

The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia

The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia

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

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms

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