Erratum: Incorrect Title of the Author. Opioid Pharmacotherapy for Chronic Noncancer Pain: The American Experience

In this review article, the title of the author was given incorrectly in the editing process. The correct information should be included only PhD.

Opioid Pharmacotherapy for Chronic Noncancer Pain: The American Experience

Chronic noncancer pain is a significant and growing public health challenge in the United States. Lacking effective alternative interventions for effective chronic noncancer pain management, many physicians have turned to opioid pharmacotherapy. Increased opioid prescribing brings not only gains in therapeutic benefit but also a higher incidence of adverse drug events including increased medication misuse and opioid related mortality. Currently the United States must confront the dual problems of widespread undertreated chronic noncancer pain and a prescription opioid abuse crisis. Withholding pain relieving drugs from patients in need is unjustifiable, yet drug diversion, abuse and adverse drug events have become major social as well as medical problems. At the heart of this crisis is the lack of definitive evidence about the risk to benefit ratio of opioid pharmacotherapy for chronic noncancer pain both on an individual case and on a population basis. This article describes the extent and severity of the American chronic noncancer pain problem and the history of opioid pharmacotherapy for chronic noncancer pain in the United States. It then discusses the concept of evidence based practice and reviews current evidence supporting opioid pharmacotherapy for chronic noncancer pain as well as adverse drug events related to opioid pharmacotherapy including misuse and abuse. Finally, it considers the conflict of providing pain relief versus protecting society and reviews steps that governmental agencies, industry and others are taking to contain and ultimately resolve the problems of excessive prescribing and conflicting priorities.

Glial Mechanisms of Neuropathic Pain and Emerging Interventions

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.