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Modulating Pain in the Periphery: Gene-Based Therapies to Enhance Peripheral Opioid Analgesia
  1. Srinivasa N. Raja, MD
  1. From the Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD.
  1. Address correspondence to: Srinivasa N. Raja, MD, Division of Pain Medicine, Department of Anesthesiology/CCM, Johns Hopkins University, 292 Osler, 600 N Wolfe St, Baltimore, MD 21287 (e-mail: sraja{at}


This article provides a brief overview of earlier work of our group on the peripheral signaling of pain, summarizes more recent studies on the role of opioids in chronic neuropathic pain, and speculates on the future of gene-based therapies as novel strategies to enhance the peripheral modulation of pain. Neurophysiologic and psychophysical studies have revealed features of primary afferent activity from somatic tissue that led to improved understanding of the physiology and pathophysiology of pain signaling by nociceptive and nonnociceptive fibers. The demonstration of peripheral opioid mechanisms in neuropathic pain suggests a potential role for these receptors in the modulation of pain at its initiation site. Our work has focused on characterizing this peripheral opioid analgesia in chronic neuropathic pain such that it can be exploited to develop novel and potent peripheral analgesics for its treatment. Ongoing research on virus-mediated gene transfer strategies to enhance peripheral opioid analgesia is presented.

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  • The author declares no conflict of interest.

  • The author thanks the financial support from the National Institutes of Health (NS-26363), Allergan, and Medtronic.