The Effects of Low Dose Naltrexone on Opioid Induced Hyperalgesia and Fibromyalgia

Abstract

Objectives: While opioids temporarily alleviate pain, the overshoot of balancing pain drivers may increase pain, leading to opioid induced hyperalgesia (OIH). Our goal was to find out what chronic opioid treatment does to pain tolerance as measured by the cold pressor test (CPT), an objective measure of pain tolerance, and to find an alternative effective treatment for chronic pain and FM.Materials and Methods: The setting was an academic addiction medicine service that has an embedded pain service. Patients had routine clinical care starting with an evaluation that included assessment of medical and psychiatric conditions. Participants were 55 patients with OIH and 21 patients with fibromyalgia; all had at least two CPTs. Treatment included a single dose of buprenorphine for detoxification. In this open-label case series, patients were treated with low dose naltrexone (LDN), a pure opioid receptor antagonist that, we hypothesize, treats OIH and FM by restoring endogenous opioid tone.Results: Comparing initial and last CPT times, those with OIH more than quadrupled their pain tolerance, and those with FM doubled theirs. This improved pain tolerance for OIH and FM was statistically significant (p < 0.0001 and p = 0.003, respectively) and had a large effect size (r = 0.82 and r = 0.63, respectively).Discussion: Results suggest that patients on chronic opioid therapy should have pain tolerance measured by CPT with detoxification and LDN provided to correct opioid induced hyperalgesia if found. FM may also be treated with LDN. The main limitation of the findings was lack of a randomized control group treated with placebo.

Low-Dose Naltrexone Co-Treatment in the Prevention of Opioid-Induced Hyperalgesia

“…In fact, when used to reverse acute morphine withdrawals in albino rats, repeated naltrexone administrations exacerbated the severity of potentiated startle and hyperalgesia [ 4 ]. In contrast, a very recent clinical study involving 55 human patients diagnosed with OIH and treated with low-dose naltrexone reported over a quadrupled level of pain tolerance as measured by the CPT and confirmed by statistical analysis (p<0.0001) [ 2 ]. These findings indicate that opioid antagonists are most effective when administered concurrently with the desired opioid agonist.…”

“…This often prompts clinicians to increase the dosage of opioids, which in turn increases pain in patients. This condition is associated with a dysfunction of the endogenous opioid system [ 2 ].…”

“…One treatment that has shown significant efficacy in trials to treat OIH is the use of naltrexone, an opioid antagonist typically used to treat substance abuse. While naltrexone was not originally designed to treat OIH, it has been shown to improve symptoms in low doses through its mechanism as a pure opioid receptor antagonist [ 1 - 2 ]. However, very high doses of naltrexone can lead to side effects such as insomnia and hallucinations, and hence the administration of the opioid antagonist should be conducted by adhering to the guidelines set by healthcare professionals [ 2 ].…”

“…While naltrexone was not originally designed to treat OIH, it has been shown to improve symptoms in low doses through its mechanism as a pure opioid receptor antagonist [ 1 - 2 ]. However, very high doses of naltrexone can lead to side effects such as insomnia and hallucinations, and hence the administration of the opioid antagonist should be conducted by adhering to the guidelines set by healthcare professionals [ 2 ]. In order to examine and understand the effects of naltrexone as a co-treatment with opioids in an objective manner, the cold pressor test (CPT) can be utilized as an objective measure of pain [ 2 - 3 ].…”

“…However, very high doses of naltrexone can lead to side effects such as insomnia and hallucinations, and hence the administration of the opioid antagonist should be conducted by adhering to the guidelines set by healthcare professionals [ 2 ]. In order to examine and understand the effects of naltrexone as a co-treatment with opioids in an objective manner, the cold pressor test (CPT) can be utilized as an objective measure of pain [ 2 - 3 ]. This review will further discuss methods of characterizing treatment for OIH, as well as evaluate the results of clinical studies that have explored the effects of naltrexone as a treatment for OIH.…”