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Roy Lab

Opioid Associated Co-Morbidities in Pain Management

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Investigator / Contact Person Sabita Roy

Research

1.Opioid Modulation of Immune function: Opioids are the gold standard for pain management postoperatively and the most prescribed analgesics for moderate to severe pain. Prescription opioid abuse has become the biggest drug problem facing the United States. Dr. Roy’s laboratory has shown that chronic opioid use and abuse significantly modulate both adaptive and innate immune system. His studies were the first to demonstrate the chronic effect of opioids on T cells and macrophages. Specifically, they show that morphine use and abuse results in the skewing of Th1 cells to Th2 phenotype. In addition, macrophage function such as phagocytosis and bacterial clearance is significantly attenuated by morphine. These results have tremendous clinical consequences in the use of morphine for pain management post surgically.

2. Opioids increase susceptibility to opportunistic Infection. More recently, Dr. Roy’s laboratory has focused on the consequence of opioid modulation of the immune system and demonstrated that chronic opioid use increases the susceptibility to opportunistic infection particularly HIV and S. pneumonia. These studies demonstrated in controlled lab experiments that morphine abuse increase risk and prevalence of HIV which was previously thought to be a consequence of non-sterile needle sharing practice. The clinical relevance of these studies suggests that patients on opioids for pain management are at greater risk for contracting infectious disease either in the hospital setting or community acquired.

3. Opioid Modulation of Gut Barrier function and Gut Microbiome. Opioid-induced constipation and sepsis have been well documented. However, the mechanisms underlying morphine exacerbation of sepsis has not been delineated. Their studies show that morphine use and abuse significantly alters the gut microbial community and results in the expansion of the pathogenic bacterial community. As a consequence gut barrier function is compromised leading to gut leakiness, gut bacterial translocation and sustained systemic inflammation. These studies have significant clinical relevance and imply that the modulation of the microbiome can be a potential adjunct therapy for patients that are on chronic morphine.

4. Chronic opioid use and peripheral neuropathy. Prolonged use or abuse of opioids results in a paradoxical increase in atypical pain (hyperalgesia) that appears to be unrelated to the original nociceptive stimulus. Despite its known limitations, mechanisms underlying opioid-induced hyperalgesia remains a significant gap in knowledge. Peripheral neuropathy has become the most common neurologic complication in cancer patients, with prevalence as high as 70 % in patients on chemotherapy. They show that chronic morphine treatment results in significant gut microbial dysbiosis with a significant decrease in bacterial communities that synthesize -glucuronidase with a concurrent reduction in glucuronidase activity. Depletion in the bacterial communities involved in the synthesis of  -glucuronidase results in a) increased accumulation M-3-G in the gut and serum and b) reduced enterohepatic recycling of morphine. They are currently investigating if decreased microbial communities associated with glucuronidase synthesis following prolonged exposure to morphine results in accumulation of M-3-G morphine metabolite and M-3-G activation of TLR2/4 leading to barrier dysfunction, bacterial translocation, sustained activation of proinflammatory cytokines contributing to peripheral neuropathy.

5. Opioid Modulation of the Gut microbiome in the context of HIV. The gut microbiota, play a significant role in maintaining gut homeostasis and gut barrier function and gut microbial dysbiosis contributes to leaky gut and sustained immune activation and inflammation. They show that gut microbial dysbiosis leads to gut barrier disruption and in HIV/ART mice in the context of opioid abuse. New therapeutic strategies targeting the gut microbiome can attenuate disease progression.