By R Carter
The 2016 CDC Guidelines for Chronic Pain Management resulted in escalating opioid hysteria to new levels, levels which resulted in healthcare professionals, clinics and hospitals abandoning well-established research and years of clinical knowledge in treating chronic pain. Any rational person would have to ask, what motivates men and women well versed in science to do such a thing, knowing that in doing so; they also abandon their sworn oath to do no harm?
That’s a question no one is willing to answer, for it is far easier to continue feigning ignorance so you can have your cake and eat it to. As chronic pain patients we have something healthcare providers want, a billable insurance policy, but with a gun pointed to their heads by law enforcement and under pressure from those fighting drug abuse, many have thrown science to the wind so they may continue to practice even though doing so requires lying to patients or kicking them to the curb.
In this article I will document what public healthcare and policy makers don’t want you to know, which is, there is no better treatment for chronic pain than opioids. This is based on our current understanding of molecular biology and pharmacology and despite claims that opioids are no more effective than Aspirin or Tylenol, I will give you the research that says otherwise, calling out the individuals who make such claims for the liars they are.
This letter MU OPIOID RECEPTORS IN PAIN MANAGEMENT published by the Department of Neurology and Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, NY, documents our current understanding of opioid receptors in human biology. The exact mechanism and action of Tylenol or Aspirin is unknown, but since our bodies create compounds which act on these receptor sites, it goes without saying that Tylenol and Aspirin are not as effective as opiates, otherwise they would have a similar propensity for these receptor sites.
In the mid 1960’s Mu receptors were postulated as the first and most abundant types of opioid receptors, occurring primarily in our brains, spinal cord, peripheral nerves and our digestive tract. By the 1970’s this information had been confirmed, was widely published and taught in our medical schools, nursing institutions and other institutions related to human biology and physiology. Since the 1970’s subtypes of the Mu (MOR) receptor have been identified including kappa (KOR), delta (DOR) Nociceptin (NOR) and zeta (ZOR).
Genetic testing identified that the opioid receptor family originated from two duplication events of a single ancestral opioid receptor early in vertebrate evolution. Phylogenetic analysis demonstrates that the family of opioid receptors was already present at the origin of jawed vertebrates over 450 million years ago making opioid receptors a common genetic trait found in nearly all species. This common occurrence across many species makes them conveniently available for research and testing of opioids on test animals so that such research can aid in the treatment of human conditions.
The first suggestion that there may be more than one class of Mu receptors came from receptor binding studies in the mid-1970s that revealed a novel site with unusual characteristics. While the Mu receptor had high binding potential for drugs like morphine, other non-narcotic drugs also bound at these receptor sites, leading to the belief that there may in fact be multiple subtypes of Mu receptors.
The opiate receptors were first cloned in 1992 with the isolation of the delta receptor DOR-1 by two independent groups. Based upon these finding, the other members of the opiate receptor family were quickly cloned, including kappa and delta receptors.
The most important class of opiate receptors that clinically remains is the class known as Mu receptors. Most of the drugs used clinically act through these receptors and understanding their actions is important in defining their pharmacology. Pharmacological studies suggested more than one class of Mu opiate receptor. This has now been confirmed at the molecular level. Although only a single Mu receptor gene has been reported, the receptor undergoes extensive alternative splicing to generate a host of splice variant receptors in nervous tissues including the brain, spinal cord and peripheral nervous system.
It is these splice variant receptors which are believed to produce different responses to different types of opiates and explains why morphine in one individual causes nausea and vomiting but another semi-synthetic type, such as oxycodone does not.
It’s been a long held hope that by identifying the splice variants, a new protein could be developed which would have the analgesic properties of opioids without the side effects which cause things such as physical dependence or respiratory depression. But so far such a chemical compound has eluded researchers, in part because it is believe that the distribution of these different receptor sites across the nervous system, through the brain, spinal cord and peripheral nervous system, preclude the possibility of creating a substance which can selectively occupy one receptor but not the others, providing adequate pain relief for the multitude of pain types that people experience.
In treating chronic pain, research and clinical trials have shown that rotating opioids from natural occurring substances such as morphine and codeine to semi-synthetic substances such as hydromorphone and oxymorphone can minimize side effect and improve pain relief in individuals who must take opioids for extended periods. This is further evidence that splice variants play some type of role in providing pain relief and that chronic use of opioids tends to reduce the effective analgesic properties of one compound over another. For this reason opioid rotation should occur at regular intervals to minimize escalation of dosage and improve pain relief for chronic pain patients.
Another concern in pain management is that because of the variety of receptor sites involved in pain, which includes Mu, Kappa and Delta, a compound which selectively occupies one receptor and not another, may prove to be inadequate for providing effective pain relief, as opposed to compounds which act on multiple receptors such as naturally occurring and semi-synthetic opioids. This fact in combination with a varied and wide distribution of receptor sites across brain, spinal cord and peripheral nerves, is why pain management remains an art as much as a science, requiring individualization of care for each person along with variable dosage amounts for each individual.
Consequently, not all patients can be managed with the same drugs. Indeed, the complexity of this clinical responses has long been known and evident. Many factors may play a role, but evidence is accumulating that much of this variability may result from the complexity of Mu receptors, all of which have yet to be identified. The molecular biology of the Mu opioid receptor gene reveals the existence of dozens of Mu receptor splice variants. Correlating these splice variants to the pharmacologically defined receptors has proven difficult. However, it seems likely that they play an important role in why patients respond so differently. As our understanding progresses, the critical question is whether or not we can utilize this knowledge to develop novel and useful analgesic lacking the detrimental actions of the currently available drugs.
Developing compounds which can selectively block the detrimental effects of opioids while still providing pain relief has been tried by using combination products which have both Mu and Kappa binding capabilities, but ultimately they have proven to have limited value because they act on multiple receptors and act across all of the nervous system. Still research continues and in February 2019 a publication was released announcing a new compound AT-121 which is a single molecule which binds to both Mu and Kappa receptors. AT-121 is 100 times more potent than morphine and blocks some of the detrimental side effects such as positive psychotropic reinforcement and respiratory depression, whether or not it prevents physical dependence has not been studied.
With all this understanding about opioid receptors and the pharmacologic compounds which act on them, including the long term side effects and methods used in dealing for those side effects, the 2016 CDC Guidelines for Chronic Pain Management chose to use research based on acute pain and opiate naïve patients, with expert testimony and review not from pain specialist but experts in opiate addiction as its basis for creating its guidelines.
These facts are the underlying evidence for why a one-size-fits-all approach to pain management or why placing universal caps and limits on dosages is an abandonment of the known science. It also demonstrates that the 2016 CDC Guidelines for Chronic Pain Management were politically motivated for solving an illegal opioid problem as opposed to providing better pain management for chronic pain patients.
Such evidence also underscores the fear and frustration of our Government in addressing an illegal drug problem. Its willingness to throw millions of Americans under a bus with caps, limits, forced tapering and termination of medical care is an effort to achieve a solution which is in fact a law enforcement problem, not a medical issue. And while current efforts go a long way at identifying a criminal element in healthcare, that remains a law enforcement issue and not something which should impose limits and restrictions on legitimate patients or doctors.
So the next time your pain specialist tells you that opiates are not effective in treating pain on a long term basis, the links in this article are evidence to the contrary. Remind them of this and to their oath to do no harm.