original abstract †Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
Opioid-induced hyperalgesia (OIH) is defined as a state of nociceptive sensitization caused by exposure to opioids. The condition is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could actually become more sensitive to certain painful stimuli. The type of pain experienced might be the same as the underlying pain or might be different from the original underlying pain. OIH appears to be a distinct, definable, and characteristic phenomenon that could explain loss of opioid efficacy in some patients. Findings of the clinical prevalence of OIH are not available. However, several observational, cross-sectional, and prospective controlled trials have examined the expression and potential clinical significance of OIH in humans. Most studies have been conducted using several distinct cohorts and methodologies utilizing former opioid addicts on methadone maintenance therapy, perioperative exposure to opioids in patients undergoing surgery, and healthy human volunteers after acute opioid exposure using human experimental pain testing. The precise molecular mechanism of OIH, while not yet understood, varies substantially in the basic science literature, as well as clinical medicine. It is generally thought to result from neuroplastic changes in the peripheral and central nervous system (CNS) that lead to sensitization of pronociceptive pathways. While there are many proposed mechanisms for OIH, 5 mechanisms involving the central glutaminergic system, spinal dynorphins, descending facilitation, genetic mechanisms, and decreased reuptake and enhanced nociceptive response have been described as the important mechanisms. Of these, the central glutaminergic system is considered the most common possibility. Another is the hypothesis that N-methyl-D-aspartate (NMDA) receptors in OIH include activation, inhibition of the glutamate transporter system, facilitation of calcium regulated intracellular protein kinase C, and cross talk of neural mechanisms of pain and tolerance. Clinicians should suspect OIH when opioid treatment's effect seems to wane in the absence of disease progression, particularly if found in the context of unexplained pain reports or diffuse allodynia unassociated with the original pain, and increased levels of pain with increasing dosages. The treatment involves reducing the opioid dosage, tapering them off, or supplementation with NMDA receptor modulators. This comprehensive review addresses terminology and definition, prevalence, the evidence for mechanism and physiology with analysis of various factors leading to OIH, and effective strategies for preventing, reversing, or managing OIH.
- “Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation,” Peter M Grace, Keith A Strand, Erika L Galer, Daniel J Urban, Xiaohui Wang, Michael V Baratta, Timothy J Fabisiak, Nathan D Anderson, Kejun Cheng, Lisa I Greene, Debra Berkelhammer, Yingning Zhang, Amanda L Ellis, Hang Hubert Yin, Serge Campeau, Kenner C Rice, Bryan L Roth, Steven F Maier, and Linda R Watkins, Proc Natl Acad Sci U S A, 2016.
- “Who Benefits from Chronic Opioid Therapy? Rethinking the Question of Opioid Misuse Risk,” Elizabeth Huber, Richard C Robinson, Carl E Noe, and Olivia Van Ness, Healthcare (Basel), 2016.
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Relationships Between Sleep Quality and Pain-Related Factors for People with Chronic Low Back Pain: Tests of Reciprocal and Time of Day Effects. Gerhart 2017 Ann Behav Med.
- Modulation in the elastic properties of gastrocnemius muscle heads in individuals with plantar fasciitis and its relationship with pain. Zhou 2020 Sci Rep.
- Association Between Plantar Fasciitis and Isolated Gastrocnemius Tightness. Nakale 2018 Foot Ankle Int.
- No Added Benefit of Combining Dry Needling With Guideline-Based Physical Therapy When Managing Chronic Neck Pain: A Randomized Controlled Trial. Stieven 2020 J Orthop Sports Phys Ther.
- Effectiveness of customised foot orthoses for Achilles tendinopathy: a randomised controlled trial. Munteanu 2015 Br J Sports Med.