Achieving effective, durable, and safe pain relief, especially in patients with chronic and/or severe pain conditions, can be difficult.
For many types of pain, prescription opioids are among the most effective analgesics. Yet, there is a growing body of evidence suggesting potential benefits of opioid antagonists, particularly naloxone and naltrexone. This is somewhat unexpected because these drugs displace opioid molecules from their neuroreceptors, and block opioids from attaching to and activating those receptors.
In a peer-reviewed, evidence-based report for Pain Treatment Topics (http://Pain-Topics.org) editor Stewart B. Leavitt, MA, PhD, describes naloxone and naltrexone pharmacology and the theoretical foundations of opioid antagonists for pain management. Titled "Opioid Antagonists, Naloxone & Naltrexone -- Aids for Pain Management," the 16-page report includes summaries of 17 studies -- case examples and clinical trials - investigating opioid-antagonist therapy in adult humans. The complete report with references can be freely accessed at the Pain-Topics.org website at http://pain-topics.org/clinical_concepts/innovations.php
Naloxone and naltrexone have been extensively studied in the past, and are FDA-approved for the treatment of alcoholism or opioid addiction (naltrexone) or opioid overdose (naloxone). A long-acting form of naltrexone for intramuscular injection also is approved for addiction therapy. These antagonists also are being used or tested as ingredients in specially formulated opioid analgesics to deter their misuse or abuse.
Leavitt notes, however, "doses of naloxone or naltrexone used in pain management are generally much smaller than in other applications; either in the 1 to 5 mg range, referred to as 'low dose,' or less than 1 mg, in microgram amounts, designated as 'ultralow dose.' In animal studies and human trials, low- or ultralow-doses of antagonists appear to enhance the pain-relieving efficacy of opioid-agonist analgesics, such as morphine, oxycodone, and others. Along with this, tolerance to and physiologic dependency on opioid analgesics, as well as certain opioid side effects, may be diminished. Furthermore, low-dose naltrexone has been successfully tested by itself as monotherapy for the management of several pain-related conditions, including Crohn's disease, irritable bowel syndrome, and fibromyalgia."
Explanatory mechanisms of action behind the benefits of opioid antagonists in pain management are still under investigation. Essentially, appropriately low doses of opioid antagonists have been postulated to "reset" the opioid-receptor system for a period of time, which seems analogous to how rebooting a malfunctioning computer clears memory, refreshes the software, and often restores normal function. With opioid-agonist therapy, the body becomes better attuned to the beneficial effects of both external opioids, such as morphine, and naturally occurring internal opioids, such as endorphins.
Clinical research to date on low- or ultralow dose applications of opioid antagonists for pain management in humans has been limited. Still, the available evidence described in this report suggests a number of possibilities that may be of interest to healthcare providers and their patients with pain, including: