Since the ancient times, opioids have been popular due to their usage to reduce pain in people. Today, opioids are popular for a different reason, they are known due to the enormous opioid addiction crisis ravaging through America. This problem originated largely from the  fact that people are forgetting how easy it is to become addicted to opioids. The other part of the addiction crisis is how addiction to prescription opioids can lead to street opioids like heroin, where deaths and consequences become much more severe. Although, there are many ways to treat physical pain without using opioids, they are just not as popular. Physical therapy, for example, is an  underestimated way to reduce pain. In physical therapy, a physical   therapist uses special techniques to improve movement, function, strength, and flexibility in ways specific to the patient to improve their pain management. “Opioid-sparing” drugs are also  up to the task to reduce pain in patients. Drugs like gabapentin are used as an opioid-sparing drug because they are administered when a patient's opioid dose must be lowered, and these drugs help relieve pain as well so opioids are not as necessary. For some patients, when the pain is not as severe opioid sparing drugs can be used by themselves to reduce pain. Whatever the case is, opioid  sparing drugs are able to reduce the need of opioids, subsequently reducing the risk of addiction. Using non-opioid analgesics is also an alternate option to opioids. Non-opioid analgesics like tylenol are often overlooked, when in reality they are very effective pain   killing agents. Part of the opioid addiction crisis is credited to doctors quickly prescribing opioids without considering using non-opioid analgesics. In addition, using new drugs like  ABT-954/PZM-21 could be an option soon as well. These drugs have showed promising results in lab tests in ways like how they can kill pain without causing a large euphoric reaction, thus  decreasing the chance of addiction. Or, new drugs like naloxone can be used to inhibit the pleasurable feelings of opioids, but not inhibit their pain killing properties. So, all of this leads to one question; what are alternative methods to reduce chronic pain without using opioids so that opioid addiction and subsequent heroin addiction will be reduced?

Before the ways to solve this problem are presented, one must understand how many people this incredibly debilitating  and popular addiction is affecting. It is easy to infer that since the opioid problem in America is referred to as an “epidemic” that it is very large, but in order to get a grasp on how big this problem actually is, there are some statistics that must be presented. In fact, “Opioids represent about 8.6% of all drug-induced fatalities reported by the American Association of Poison Control Centers.” (Mowry, 2). Even though this epidemic is so large spread, it has actually only become a very serious problem recently. Since about the early 2000’s- “Prescription pain reliever overdose deaths among women increased more than 400% from 1999 to 2010, compared to 237% among men.” (Center for Disease Control and Prevention). There are also dramatic effects on specific populations. For example, from 2010-2013 heroin overdose deaths have tripled in women, from .4-1.2 per 1,000 women. Thus, it is evident how greatly this problem is affecting the lives of Americans today.
There are three types of opioids, there are natural, semisynthetic, and fully synthetic opioids. Examples of natural opioids include opium, morphine, and codeine. Semisynthetic opioids include oxycodone, hydrocodone, and heroin. Fully synthetic opioids include methadone and fentanyl. All types of opioids have the same function, they all bind with the mu, kappa, and delta opioid receptors. These opioid receptors are located all throughout the body, especially in the spinal cord and the reward system of the brain. The reward system of the brain includes the areas responsible for the perception of pain and reward. These areas in the brain include the ventral tegmental area (VTA), the nucleus accumbens the prefrontal cortex, arcuate nucleus, amygdala, locus coeruleus, and the periaqueductal gray area. When opioids bind with the three opioid receptors in the reward system there is an intense euphoric feeling throughout the whole body. A user may experience “a warm flushing of the skin, dry mouth, and a heavy feeling in the extremities.” (National Institute on Drug Abuse, 1). Due to all these intense pleasurable feelings it can be easy for a user to  become fond of opioids and eventually become addicted once one is taking them for a short period of time. In addition to how opioids work in the body and how they can cause pleasurable feelings, opioids are generally easy to obtain. Often times, a doctor will over prescribe a patient opioids so he/she will have left over pills after their pain has subsided. In the “Opioid Addiction 2016 Facts & Figures”, it is stated “People often share their unused pain relievers, unaware of the dangers of nonmedical opioid use. Most adolescents who misuse prescription pain relievers are given them for free by a friend or relative.” (Cicero). When people do not realize the severity of opioids they can easily become addicted before they realize it, or overdose. With all these factors associated with opioid use, it is plain sight how easy it is to become addicted to opioids, hence the severe opioid epidemic in America today.

Heroin is a very dangerous street drug. It is often associated with other street drugs like cocaine, meth, and MDMA. What some people may not know is that heroin is an opioid, therefore it has more in common with opioids prescribed by doctors that it does with drugs like cocaine, meth, and MDMA. Heroin is a semi-synthetic opioid, meaning it is not a natural opioid like morphine, but it is also not completely man made like methadone. Heroin is derived from a natural opioid (morphine) so it is classified as a semi-synthetic opioid. When a doctor prescribes opioids to a patient and the patient becomes addicted and their prescription is cut off, there is a reasonable chance that the patient can turn to a street opioid like heroin due to it’s low cost and relative easy access. Like all opioids, heroin is a depressant drug so it slows down all bodily functions. Because heroin is such a strong drugs and slows down all bodily functions, it lowers the heart rate to and breathing to dangerously low levels that can be life threatening (National Institute of Health).  In addition as to how slowed breathing caused by heroin can be very dangerous, slowed breathing can cause serious problems like comas (Fortuna, 1). Not only can heroin easily kill someone in a few hours from things like slowed heart rate and breathing, but it is also very detrimental to human health in the long term. “Studies have shown some deterioration of the brain’s white matter due to heroin use, which may affect decision-making abilities, the ability to regulate behavior, and responses to stressful situations.” (National Institute on Drug Abuse). Even if a user of heroin does find help and is able to get themselves off of heroin use, the long term effects like decreased white matter in the brain are permanent. Perhaps the most scary part of opioid addiction evolving into heroin use is the “street” aspect of heroin. When someone wants to obtain heroin off the street, the dealer they obtain it from could have added/laced the heroin with other substances that increase the danger and negative side effects of heroin. For example, heroin can be cut with a toxic additive like quinine. Quinine is a medication that is used to treat malaria and can have very harmful effects on the body like kidney damage, arrhythmias, severe bleeding problems, severe allergic reactions, and also death. When heroin is cut with quinine there is an increased chance of experiencing severe side effects like those mentioned previously (Watkins). Another serious problem with street heroin is the potency of each batch. Each batch produced can have a wide range of actual heroin in it. One batch could have 3% heroin, and the next could have 99% heroin (Johns Hopkins University). This extremely increases the chance of overdose because a user would have to take a couple of doses to get high with one batch that has a lower heroin content, then when he/she uses again with a different batch and he/she is unaware the heroin content is higher and then takes the same amount of dosage, he/she could be dead within a few hours. Therefore, heroin is a very dangerous drug that should be taken seriously and one can turn to using heroin and experiencing all of the negative side effects due to a couple prescriptions of opioids.

The solution to stop opioid addiction and heroin use would be to eliminate the need to use opioids by replacing them with alternate methods to kill pain. Luckily, there are multiple alternatives to opioids. Unluckily, they are not as popular and resorted to as often as opioids are. One alternative way to kill pain without opioids is the use of ABT-594. In lab tests, ABT-594 has shown to have pain killing properties similar to morphine but does not share the addictive properties associated with morphine, “A potent (inhibition constant = 37 picomolar) neuronal nicotinic acetylcholine receptor (nAChR) ligand called ABT-594 was developed that has antinociceptive properties equal in efficacy to those of morphine across a series of diverse animal models of acute thermal, persistent chemical, and neuropathic pain states…  In contrast to morphine, repeated treatment with ABT-594 did not appear to elicit opioid-like withdrawal or physical dependence.” (Decker). With promising results from tests involving ABT-594 it is being put through further clinical trials so that it could hopefully be used to as a go to pain reliever in humans soon. Another promising substance that has pain killing properties similar to morphine but without the addictive properties of morphine is PZM-21. PZM-21 is also an experimental opioid analgesic. “Specifically, the more PZM 21 the mice were given, the more pain relief they experienced. The compound mitigated 87% of the rodents’ pain, compared with 92% for morphine...But the truly thrilling finding was that PZM 21 did not stimulate the dopamine pathways in the brain, which are the reward systems known to fuel addiction. In other words, the mice were largely pain-free, but they didn’t get high.” (Fidler). With encouraging results like this from PZM-21, it is being looked at to be one of the more popular alternates to use for pain killing rather than opioids. On the rather less talked about side of alternate painkillers are ingredients in non-opioid analgesics that can be used by themselves to reduce pain. For example, acetaminophen  is an ingredient used in tylenol. Even when it is used by itself, it is an  useful pain reliever and is highly recommended by doctors (Mahoney).

Perhaps the most promising and popular alternative painkiller being developed is naloxone. Naloxone works by blocking the TLR4 receptor. TLR4 is a receptor in the immune system that is responsible for enhancing the euphoric sensation experienced when an opioid is put into the body. Researchers found that if TLR4 could be blocked somehow, then when a patient takes an opioid, he/she would only experience the pain killing characteristics of the opioid not the euphoric sensation. Through research, it has been found that the drug naloxone as proven to block the TLR4 receptor. “Studies show that the drug naloxone blocks the immune response to morphine, shutting down additional pleasure resulting from continued use of opioids. If the TLR4 is blocked dopamine is no longer produced, and this is the chemical that creates a sense of “pleasure” that opiate users experience.” (Sober Living By the Sea). Therefore, if naloxone is taken with an opioid then the user of the opioid will not feel the large amounts of pleasure caused by opioids, but only the pain killing experience caused by opioids. These promising finding have caused researchers to experiment further with naloxone in hopes to popularize this useful drug.

There are also drugs that are being prescribed by doctors right now that could be utilized to kill pain. The drugs known as “opioid sparing” drugs are commonly used among patients who suffer from opioid hyperalgesia. Opioid hyperalgesia is a condition, usually in people who have been taking opioids for an extended period of time, where the opioid user becomes more susceptible to pain. In an opioid addict with opioid hyperalgesia, opioid sparing drugs like gabapentin could be administered in order to decrease the opioid hyperalgesia. This category of drugs could also be used to wean an addict off of opioids, or at least reduce their dosage. For example, if a patient has been taking opioids for an extended period of time and has developed a very high tolerance it is more practical that he/she would be slowly taken off of the opioid by reducing the dosage by implementing opioid sparing drugs into their opioid consumption regimen rather than completely cutting off the opioid dosage. Gabapentin is able to do this by reducing the amount of substance P. Substance P is a neurotransmitter that is responsible for sending pain signals along the body’s nerve pathways. This means that if substance P is reduced then the pain signals are transmitted more slowly, thus altering pain perception in a human to mimic pain killing effects of opioids (Rehab). Since gabapentin and other opioid sparing drugs do not interact with opioid receptors, they are not addictive like opioids. Since opioid sparing drugs like gabapentin are able to be used to mimic the effects of opioids, it is obvious they can be used in certain situations by themselves to kill pain. Although opioid sparing drugs could not be used to completely replace opioids, they can dramatically reduce the need for opioids. Part of the problem with opioids that is going on today is that doctors can prescribe a patient opioids when they are not actually necessary. In cases like these, a drug like gabapentin could be brought into play to reduce the risk of opioid addiction and possibly heroin addiction. Also, opioid sparing drugs would be able to reduce a patient’s dependence for opioids slowly instead of cutting off his/hers prescription all at once, which would make it much more likely for a patient to turn to dangerous drugs like heroin to get the same euphoric feeling. Lastly, and possibly the most intriguing aspect of a drug like gabapentin, is that it is very hard to overdose on opioid sparing drugs, unlike opioids. The common side effects of opioids include drowsiness, indigestion, and headache (Derm)

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Although a drug like gabapentin can be used while opioids are still in play, some people argue that interacting with opioid receptors at all is always a high risk scenario. Therefore many researchers are looking for different receptors that could be of use to reduce pain. Cannabinoid receptors are among the more popular receptors being researched. Marijuana has gained massive support as a pain killing agent due to the recent legalization of medical marijuana in some states in the U.S.. Dale Deutsch of Stony Brook University and colleagues scanned many compounds to figure out which ones would be able to contain an enzyme that could break down anandamide.  Anandamide is a cannabinoid neurotransmitter, an increase of anandamide would activate natural cannabinoid receptors. Deutsch and colleagues have found that an activation of cannabinoid receptors would result in the reduction of pain (Grens). Although cannabinoid receptors may not work as well as opioid receptors in killing pain, it is important to note that the use of marijuana is much less debilitating to the body than opioids and the use of marijuana presents less of a risk of becoming addicted and providing a gateway to more serious and dangerous street drugs.

One last notable way to reduce pain without opioids would be uniquely expressed sodium channels in pain fibers. Recently published research shows that a compound in centipede venom has proven to decrease pain in rodents better than morphine did. The target of the venom is a sodium channel that is not shown to function in people with a inability to feel pain (Wolf).

Methods like using “opioid-sparing” drugs, using non-opioid analgesics, using new drugs like ABT-954/PZM-21, and using drugs like naloxone to inhibit pleasure from opioids can be used as alternatives to treat pain rather than solely using opioids. In order to put this information to use the population of America must become familiar with all the problems/solutions associated with the opioid epidemic. If this information is popularized and familiarized with the American population, than these methods will be available for doctors to utilize and in turn reduce the opioid epidemic in America.