Investigation of Immunologic Responses Following Chronic Opioid Use to Treat Lower Back Pain

Although there are many health challenges facing the United States today, prescription opioid abuse merits special attention as it has reached epidemic proportions. While not all abusers of prescription opioids have received a legitimate prescription, some legitimate medical users will eventually fall into a pattern of misuse, and many legitimate prescriptions will eventually be diverted for non‐medical use. Therefore, eliminating sources of unnecessary chronic use of these products could have a substantial impact on the future of such abuse. Over 55 million opioid prescriptions written are for patients with back pain or osteoarthritis, despite a lack of clear benefit for chronic opioid use in these conditions. Intriguingly, while acute opioid use can lead to immunosuppression, chronic opiate use can result in ongoing inflammation and hyperalgesia. This suggests that opioid drugs may induce idiosyncratic immunogenic responses over the course of chronic use. Intriguingly, previous preclinical research has uncovered a link between chronic administration of abused substances and the formation of advanced glycation end products (AGEs) and antibodies in rodent serum. Furthermore, the presence of opioid‐reactive antibodies have been sporadically reported in humans with a history of substance abuse or occupational exposure. However, whether the necessary conditions to generate these reactions are present in legitimate medical users of chronic opioid therapy remains unknown. We thus assessed whether chronic use of opioids in humans can generate self‐reactive antibodies that diminish the long‐term efficacy of analgesics in patients with lower back pain. To accomplish this, we recruited human subjects that had at least a 6‐month history of lower back pain, including individuals who had been either chronically taking hydrocodone or oxycodone, as well as opiate naïve individuals. These individuals received a questionnaire regarding their back pain and opiate use history, as well as educational materials regarding opioid alternatives, and a medication use diary. A blood draw was taken at this baseline visit, as well as at a 3‐month follow‐up visit where a follow‐up questionnaire was completed and the medication use diary was collected. The blood samples were assessed for anti‐opioid antibodies using ELISA. To date, 22 subjects have completed the study protocol, and preliminary analysis of the tissue samples provided indicates a low level of anti‐opioid IgG antibodies exists in this population. This result indicates that further assessment of the serum samples for additional antibody isotypes and AGE markers is warranted to assess whether chronic opioid use can generate anti‐opioid antibodies through an AGE‐mediated mechanism. Support or Funding Information This work was made possible by a generous grant provided by the Skaggs family through the ALSAM Foundation, and supported by additional funds from NIH (F32DA043323) and the UW‐Madison OVCGRE (AAD4442).Hypothesized cycle showing opioid‐induced AGE formation, subsequent antibody generation, inflammatory and pain response, and opioid use.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .