How do Pain Relievers Work?


Pain has been defined as "an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage." It is a vital function of the nervous system in notifying us with warning of potential or actual injury.

First, lets explain the pain pathway:

  1. Lets say you accidentally prick your finger with a sharp needle - this would lead to tissue damage which is recognized by specialized nerve cells called nociceptors. These stretch from the spinal cord to your skin, muscles, joints, internal organs and even teeth. Like most receptors, they too conduct electrical signals, but unlike other nerve cells, nociceptors only activate when something happens that can cause or is causing damage. In my example you have pricked your finger, as opposed to gently touching (which would only activate regular nerve cells, indicating to your brain that you are touching something, but it isn't causing any harm). A certain threshold has to be passed for nociceptors to fire their action potentials. 
  2. Once the nociceptor has been activated, an electrical signal is transmitted up a nerve fibre
  3. As the nerve fibre travels up your arm towards the brain, it amalgamates with many other fibres to form the peripheral nerve. The signal is then passed onto neurons within the peripheral nerve into the spinal cord
  4. Within the spinal cord is a section called the dorsal horn where the signal is transmitted from one neuron to another via diffusion of neurotransmitting chemicals (acetylcholine) over a synapse which then goes to the brain. 
  5. In the brain, the signal passes into the thalamus which relays the information to three sites:         1/ somatosensory cortex [physical sensations]                                                                               2/ frontal cortex [in charge of thinking i.e. how you will act to the pain]                                       3/ limbic system [emotional response]               
                         




A-delta fibres carry information much faster due to being myelinated (i.e coated in myelin, a fatty insulator that speeds up impulse transfer). C fibres do not have this. This explains why, on pricking your finger, the first type of pain you feel is sharp, followed by a slower ache.

Types of Pain
  • Nociceptive  - Caused by injury to bodily tissues 
  • Neuropathic - Caused by problems referring to nerves, spinal cord or brain e.g. inflammation                           of nerves
  • Psychogenic - Caused by psychological, mental, emotional or behavioural factors 
  • Acute - Short lived pain, typically a symptom of injury or disease at the tissue level. 
  • Chronic -  Also known as persistent pain, caused by ongoing tissue damage such as in forms of arthritis or osteoporosis. Usually due to the hypersensitivity of nerve receptors and the brain failing to dampen down pain signals. 
Pain Relievers

When tissues are damaged, a chemical called arachidonic acid is secreted (the chemical at the top of this article). This acid is broken down by two enzymes called COX-1 and COX-2 into prostaglandin H2. Prostaglandin H2 is then converted further into a plethora of chemicals e.g. TXA2, PGD2, PGE2 & PGF2 which raise body temperature, cause inflammation and lower the pain threshold. 


For this diagram, think of the enzyme as COX-1/2 and the substrate as arachidonic acid. Arachidonic acid has a complementary fit into the active site of COX which allows it to be broken down into its constituents. This is where pain relievers e.g. ibuprofen, aspirin, naproxen etc. 

Aspirin is needle-like in structure, it binds to the active site of COX, blocking the site so arachidonic acid cannot bind and breakdown into the chemical constituents to cause the symptoms of pain. This permanently deactivates COX. 

Ibuprofen is more a temporary solution, because COX can choose to expel it from its active site, but this is not instant, rather happens over hours. 


Further Reading // Sources

http://teachmephysiology.com/nervous-system/sensory-system/pain-pathways/

https://www.mydr.com.au/pain/pain-and-how-you-sense-it

https://www.ted.com/talks/george_zaidan_how_do_pain_relievers_work



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