The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia

Abstract

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.

Dorsal Root Ganglion Stimulation to Treat Chronic Shoulder Pain: A Case Report

“…One plausible mechanism of action for DRG-S involves stimulation of low-threshold mechanoreceptors that in turn trigger spinal endogenous opioid receptor activation. 13 Analgesia through opioid receptor activation is known to be particularly effective for all types of chronic pain, including nociceptive pain. 14 It has also been postulated that neuromodulation with bioelectronic medicine therapies such as DRG-S that target the autonomic nervous system may be able to treat osteoarthritis-related pain and pathogenesis by reducing related neurogenic inflammation and preventing maladaptive nervous system plasticity.…”

Brain stimulation for chronic pain management: a narrative review of analgesic mechanisms and clinical evidence

“…However, despite these reports, which have not been fully confirmed, the exact mechanism remains to be determined. Nevertheless, the potential for disorienting psychoactive, respiratory depression, and other side effects in chronic pain patients who manage only with opioid drugs may be the impetus for an in-depth discovery of the mechanisms at play here and thus originate novel effective and tolerable treatment paradigms to lessen the suffering of patients [ 50 ].…”

Molecular and Cellular Mechanisms of Neuropathic Pain in Aging

“…Pain perception is regulated via the ascending nociceptive pathway and the descending modulatory system, both of which represent the main conduits for nociceptive signaling (Table ). The reaction to noxious stimuli is a multifaceted process mediated by diverse cerebral structures. These structures comprise the anterior cingulate cortex, insular cortex, thalamus, and periaqueductal gray matter …”