Opioid Use and Abuse

           Opioids are a class of drug that are primarily used for the purpose of pain management. However, when abused or used in a neglectful manner, they can produce harmful consequences. The structure of opioids is similar to neurotransmitters that are naturally found throughout the body; opioids work by attaching to and activating neuronal receptors, which blocks pain signals. Once opioids bind to the receptors, the sensitivity of the receptors is consequently decreased, preventing other neurotransmitters from binding to them. With the growth of opioid abuse and the rise in the opioid epidemic in the U.S., prescription drugs, such as morphine and hydrocodone, as well as illegal drugs, such as heroin, are under stricter watch with respect to prescribing and dispensing.

On December 11, 2017, Dr. Folabomi Oladosu presented her research at Loyola University Chicago, which involved the study of developing sensitivity to pain in regards to the prolonged use of opioids, which is referred to as opioid-induced hyperalgesia. This disorder results from the long-term use of opioids and, ironically, propagates the problem that it was intended to fix by increasing one’s sensitivity to pain. The underlying mechanism of this condition is still largely unknown, however, Dr. Oladosu’s research sought to understand the role of the splice variant, MOR-1K, in the development of opioid-induced hyperalgesia. The MOR-1K is a g-protein coupled mu opioid receptor, which may be implicated in the development of opioid-induced hyperalgesia due to its role in the increased sensitivity to pain as well as its ability to produce excitatory signals. In her study, Dr. Oladosu administered morphine to different strains of mice: C57BL/6J, 129S6 and CXB7/ByJ. Brain and cerebrospinal fluid samples were collected for each strain of mouse 24 hours after the administration of morphine. After purifying, homogenizing, and performing PCR on the RNA from each sample, the analysis of gene expression was conducted. The results indicated that each strain of mouse differed in its response to the administration of morphine. The 129S6 strain of mice displayed a decrease in MOR-1K levels in response to noxious stimuli, while the CXB7/ByJ strain of mice displayed an increase in the MOR-1K levels to the same stimuli. The CXB7/ByJ strain of mice displayed high sensitivity to pain in response to the same noxious stimuli that were presented to the other mice, while also exhibiting high levels of MOR-1K gene expression. This study illustrated the increase in pain sensitivity correlating with the increase in MOR-1K levels, which suggests that the MOR-1K receptor plays a crucial role in the development of opioid-induced hyperalgesia.

The effects of opioid-induced hyperalgesia are similar to the effects experienced by those who face opioid drug withdrawal or tolerance. Therefore, this condition may also play a role in opioid abuse and overdose, contributing to the opioid epidemic that is prevalent in our society at present. In Kelly Servick’s article, it was indicated that there are varying opinions regarding the condition of opioid-induced hyperplasia. While there are some researchers that are attempting to understand the mechanism behind it in order to decrease its prevalence, there are others who are either unaware of this condition or are skeptical of its significance. This skepticism has resulted in healthcare providers prescribing higher doses of opioids to reduce the pain that patients experience as a result of opioid-induced hyperalgesia, rather than reducing the dose. A correlation between the increase in the prescribing of higher doses and the increase in prescription opioid overdoses was noted. These events have increased four-fold over the past twenty years in the U.S., resulting in 21,000 deaths alone in 2014. This impulsive opioid prescribing has further contributed to the opioid epidemic that persists in the U.S. today, which represents the harm that healthcare providers are doing to their patients. Another problem that is discussed in this article relates to the discrimination between opioid-induced hyperalgesia and drug tolerance as they produce similar physical effects with the affected individual experiencing increased sensitivity to pain. Pain researchers have attempted to differentiate between the two conditions in a laboratory setting my exposing affected individuals to painful stimuli to no avail. This has led pain researchers to set up a clinical trial that would test ketamine and guanfacine in reducing the symptoms produced by opioid-induced hyperalgesia. The ketamine would work by blocking the effects of opioid-induced hyperalgesia. By blocking NDMA receptors to glutamate, which is released by sensory neurons, they can also block the transmission of pain signals, similar to the effects of opioids. Additionally, guanfacine would work by inhibiting the release of glutamate, which would also result in the blockage of pain signaling. Another significant research lab in Shanghai has indicated that blocking the release of inflammatory molecules by astrocytes could potentially reverse the effects produced by opioid-induced hyperalgesia as well as opioid tolerance in rat models. The research that is being conducted in order to understand and potentially prevent opioid-induced hyperalgesia is significant and can enable those living with chronic pain employ safer and more effective courses of treatment.

The research presented by Dr. Oladosu regarding the role of the MOR-1K receptor in opioid-induced hyperalgesia and the article discussing the correlation between opioid-induced hyperalgesia and the opioid epidemic present the significance of the issue surrounding opioid use use and abuse. By understanding this class of drug more comprehensively, efforts can be made to develop alternatives to opioid use in order to decrease the prevalence of opioid-induced hyperalgesia. Additionally, further research would allow us to potentially eliminate the persistence of the opioid epidemic that plagues our country today.

Works Cited

Oladosu, Folabomi A., et al. "Mu opioid splice variant MOR-1K contributes to the development of opioid-induced hyperalgesia." PloS one 10.8 (2015): e0135711.

Servick, Kelly. “Why painkillers sometimes make the pain worse.” ScienceMag. American Association for the Advancement of Science, 03 November, 2016. www.sciencemag.org/news/2016/11/why-painkillers-sometimes-make-pain-worse. doi:10.1126/science.aal0341. Accessed 10 December 2017.