By tracing the history of Analgesics, we can illustrate their use in the world today. From ancient remedies, to the rise of opioids and non-opioid options, tracking the history of pain relievers shows the progress of modern medical science, and how it is not always linear. This series will is a brief history of Analgesics, starting with pain relievers prior to the synthesis of morphine in the early 19th century, up to the present day. This article will focus on non-opioid analgesics.
The very term “non-opioid analgesic” is instrumental in understanding the presence opioids have in the current pain management landscape. For most of history, pain relief medications did not contain opioids. Yet from the synthesis of morphine in the early 19th century to the present day, opioids have had such a considerable stronghold in the medical world that ‘non-opioid analgesic’ must be used to describe the large selection of pain medications that do not have an opioid base. While opioids have their drawbacks (as discussed in this series’ previous article), their track record in alleviating pain is well documented and has earned them this prominence. However, this is not to say that non-opioid analgesics (NOAs) are ineffective or useful only for minor levels of pain. NOAs have been shown to be very effective in dealing with pain of varying causes and severity, and the promise new NOAs have shown in clinical trials brings optimism that opioids may not always need to be the last, best resort for pain. Here, we will discuss the recent history of NOAs, and how they are being developed in the present day.
Aspirin
In this series we have briefly touched on the analgesic properties of the willow tree, and how from the salicin found in its bark, scientists were able to synthetize acetylsalicylic acid, better known as aspirin. What was not mentioned was how groundbreaking aspirin was as an analgesic. Since its introduction in the late 1890s, aspirin has been one of the most widely used drugs in the world.[1] Today, it is still a popular choice for common aches and pains, and inflammatory conditions like arthritis. In addition to this, aspirin has displayed efficacy in treating non-pain conditions. Its cardiovascular benefits are well documented in lessening the severity and occurrence of heart attacks and strokes. Simply put, aspirin is one of the most important medications – analgesic or otherwise – ever introduced, and its success paved the way for future NOAs.
Acetaminophen
Acetaminophen, also known as Paracetamol, was first synthesized in the 19th century, but was not sold commercially until the 1950s. An alternative not just to opioids but to other early-modern NOAs like aspirin, acetaminophen became a pivotal player in the realm of non-opioid analgesics. Seen as a safer alternative to aspirin (which was known to exacerbate ulcers and other gastrointestinal conditions),[2] acetaminophen quickly became one of the most popular over-the-counter medications ever sold, and is still an excellent option when dealing with mild to moderate pain.
NSAIDs
Following the worldwide popularity of aspirin and acetaminophen, the mid-20th century saw an explosion in the development of NOAs, with non-steroidal anti-inflammatory drugs (NSAIDs) being one of the innovate drug classes introduced during this time period. Ibuprofen, the most popular NSAID in terms of worldwide usage, was first discovered in 1961 by Stewart Adams.[3] With its potent anti-inflammatory and analgesic properties, ibuprofen proved very successful as a treatment for common aches and pains, and its prominence led to future NSAIDs such as naproxen and indomethacin.
Tetrodotoxin: the next step
Now, two decades into the 21st century, NOAs are potentially being revolutionized once more. For decades, a drawback of NOAs were that they were primarily used to treat mild to moderate pain. They were safer than opioids, but also less effective in managing severe pain, allowing for their over-the-counter sale but limiting their viability as genuine opioid alternatives. Today, there are clinical trials being conducted for newer, more potent NOAs that may be able to solve this problem, such as Tetrodotoxin (TTX). As we have covered before, TTX has shown genuine progress in treating a variety of serious pain conditions, and this viability gives hope to the idea that NOAs may not be relegated to minor pain treatment for much longer.
The modern era of NOAs reflects the pressing need medical science has for opioid alternatives. As incidence of opioid dependence and overdoses grows, having medications that can treat pain without the inherent side effects of opioids is a top priority. On a larger scale, tracking the history of analgesics in general, from ancient remedies to cutting-edge NOAs, allows for an understanding of how imperfect pain treatments have been. Early treatments lacked the medical science needed to ensure they were administered in safe doses. Modern pain treatments have had to deal with the issue of trade-offs: choosing between the more effective but less safe route of opioids, or the reduced potency and better safety profile of NOAs. As of now, the ‘perfect’ analgesic has proven elusive, but improvements and innovations inspire hope that pain will be treated in increasingly more safe and efficient ways. Pain treatment has come very far since ancient times, and there are still new and promising avenues to explore.
[1] Montinari, M. R., Minelli, S., & De Caterina, R. (2019). The first 3500 years of aspirin history from its roots – a concise summary. Vascular Pharmacology, 113, 1–8. https://doi.org/10.1016/j.vph.2018.10.008
[2] Ayoub, S. S. (2021). Paracetamol (acetaminophen): A familiar drug with an unexplained mechanism of action. Temperature, 8(4), 351–371. https://doi.org/10.1080/23328940.2021.1886392
[3] Rainsford, K. D. (2012). Ibuprofen: From invention to an OTC therapeutic mainstay. International Journal of Clinical Practice, 67, 9–20. https://doi.org/10.1111/ijcp.12055
DISCLAIMER:
Halneuron ® is still being developed and tested in clinical trials and has not yet been
approved for sale by Health Canada, the United States Food & Drug Administration (US
FDA), or any equivalent medical authority. This article contains forward-looking
statements and information under applicable Canadian securities laws (collectively
“forward-looking statements”), including statements regarding the safety and
therapeutic efficacy and utility of Halneuron® and Tetrodotoxin (TTX) as a peripheral-
acting, non-opioid analgesic. Statements in this document regarding future expectations,
beliefs, goals, plans, or prospects constitute forward-looking statements that involve
risks and uncertainties, which may cause actual results to differ materially from the
statements made. For this purpose, any statements that are contained herein that are
not statements of historical fact may be deemed to be forward-looking statements.
Without limiting the foregoing, the words “believes”, “anticipates”, “plans”, “intends”,
“will”, “should”, “expects,” “tolerates,” “projects,” “manages,” “reduces,” “shows,”
“promises,” “outperforms,” “affirms”, “acceptable”, “accepts”, “progress,” “establishes”, “continued advancement”, “in time,” and similar expressions are intended to identify forward-
looking statements. You are cautioned that such statements are subject to a multitude of
risks and uncertainties that could cause actual results, future circumstances, or events to
differ materially from those projected in the forward-looking statements. These risks
include, but are not limited to: those associated with the success of research and
development programs, the Company’s ability to raise additional funding and the
potential dilutive effects thereof, the regulatory approval process, competition, securing
and maintaining corporate alliances, market acceptance of the Company’s products, the
availability of government and insurance reimbursements for the Company’s products,
the strength of intellectual property, reliance on subcontractors and key personnel and
other risks detailed from time-to-time in the Company’s public disclosure documents and
other filings with the U.S. Securities and Exchange Commission and Canadian securities
regulatory authorities. Forward-looking statements are developed based on assumptions
about such risks, uncertainties and other factors, including, but not limited to: obtaining
positive results of clinical trials, obtaining regulatory approvals, TTX is a more potent
analgesic than standard analgesics, TTX has shown genuine progress in treating a variety of serious pain conditions, safety of product, effectiveness of drug, more safe than opioids, ability to treat a variety of serious pain conditions, has shown proven efficacy in trials, general business and economic conditions, the Company’s ability to successfully develop and commercialize new products, the assumption that the Company’s current good relationships with third parties will be maintained, the availability of financing on
reasonable terms, the Company’s ability to attract and retain skilled staff, market
competition, the products and technology offered by the Company’s competitors, and the
Company’s ability to protect patents and proprietary rights. Forward-looking statements
are made as of the date hereof, and the Company disclaims any intention and has no
obligation or responsibility, except as required by law, to update or revise any forward-
looking statements, whether as a result of new information, future events, or otherwise.
