I’m sorry about the image quality; the website wouldn’t allow the scan that wasn’t bad.

My piece visually depicts the means through which various types of painkillers inhibit or antagonize pain perception. It also means to show in some small detail the specifics of what nociceptors are and how they work.

Nociceptors are the nerve cells responsible for your perception of pain. Without nociceptors, it is impossible to perceive noxious stimuli, the range of extreme conditions which your body has determined through evolutionary means should invoke a pain response.

To the body, there are three ‘types’ of pain. These are physical, thermal, and chemical. Nociceptors are typically specialized into the perception of one of these types of pain, although polymodal nociceptors, which detect several, do exist. Many of the body’s nociceptors are also ‘silent’, which means they do not detect pain under normal conditions. Instead, they amplify and inform in excess the pain of a serious injury, like a deep cut.

These specialized nerve cells make use of a variety of specialized proteins to detect these conditions. For example, TRPV1, a receptor known for its sensitivity to capsaicin, also detects heat, and triggers the sensation of being scalded. A separate protein exists which detects extreme cold, physical trauma, and so on.

There is much more to know about this one type of nerve cell! So much. In fact, much of how they work isn’t even known by current medical science. But, for our purposes this covers the basics of what they are and how they work.

So, painkillers: One means of managing pain is the reduction of inflammation. NSAIDs, nonsteroidal anti-inflammatory drugs, do this. They operate by the inhibition of a specific group of enzymes, called COX. COX-2, the specific enzyme which drug manufacturers aim to block, catalyzes the formation of several other molecules. One of these, prostaglandin, is a hormone-like lipid which induces inflammation. The suppression of the enzyme prevents the production of prostaglandin, reducing inflammation over time. Unfortunately, the suppression of COX enzymes has other negative impacts on bodily function, including the creation of stomach ulcers.

Of course, analgesics (painkillers) also operate through the direct suppression of nerve signals. Alcohol is probably the most famous drug which does this. Alcohol antagonizes receptors, reducing the effect of several major neurotransmitters. This has many secondary impacts on the nervous system, not to mention its other negative health impacts, making alcohol a poor choice for pain management.

Then, there are opiates! Probably the most iconic painkiller, opioids act on the ‘opioid receptors’ of the central nervous system. They are agonists, as opposed to antagonists, of these receptors, making them unique from alcohol or NSAIDs, and many other painkillers. This is because opiates are similar to the same chemicals that activate opioid receptors. They simply tell the body to induce analgesia, and it does so.

They typically induce a whole body analgesia through the activation of mu receptors. This receptor causes many secondary effects, but are pleasantly the most manageable of the side effects that activating opioid receptors could give. Most would agree that constipation, respiratory depression, and physical addiction are less problematic than depression, dissociative/hallucinative episodes, stress, seizures, and a constant sense of unease.

So, that’s it! Nociceptors are a unique and not overly well understood variety of neuron. And interestingly, many of the most common analgesics used don’t disrupt their function directly, but instead activate or suppress other stimuli which affect nociceptor transmissions, or which suppress the signal before it reaches the hypothalamus. Unfortunately, analgesics also host a wide variety of dangerous side effects, regularly making severe pain management an exercise in picking the lesser evil.

Citations:

O. (2023, November 1). Nociceptor. Wikipedia. https://en.wikipedia.org/wiki/Nociceptor

Buidhe, B., & Maxeto0910, M. (Eds.). (2023, November 4). Analgesic. Wikipedia. https://en.wikipedia.org/wiki/Analgesic

W. R. Martin, (1967/12/1). Opioid Antagonists. Pharmacological Reviews. Issue 4, volume 19. http://pharmrev.aspetjournals.org/content/19/4/463.abstract

National Research Council (US) Committee on Recognition and Alleviation of Pain in Laboratory Animals. Recognition and Alleviation of Pain in Laboratory Animals. Washington (DC): National Academies Press (US); 2009. 2, Mechanisms of Pain. Available from: https://www.ncbi.nlm.nih.gov/books/NBK32659/