Related Experiment Video
Updated: Nov 15, 2025

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
The Effects of Low Dose Naltrexone on Opioid Induced Hyperalgesia and Fibromyalgia
Daniel Jackson1, Sunita Singh2, Yanli Zhang-James1
1Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, United States.
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.
Related Concept Videos
Analgesia and Pain Management
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Opioid Receptors: Overview
Opioid Analgesics: Morphine and Other Natural Cogeners
Nociception
Drugs for Treatment of Diarrhea-Predominant IBS
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...

