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Sorting Medicine

The Role of Opioid Receptors in the Nervous System: Implications for Pain Management and Addiction

This paper will review opioids, how they are used to suppress pain and whether they are safe and viable. Opioids (sometimes referred to as narcotics) are a wide range of pain-relieving drugs derived from opium. They are medications prescribed by doctors to treat prescribed or persistent pain. They are consumed in pill form, but they can also be taken as lozenges or lollipops. They can also be taken through the veins with injections or IV. Another method of ingesting them is through placing patches on the skin or even with the help of suppositories. 


The discovery of these enhanced substances is considered to be one of the great advancements in the medical industry. Opioids date back to the growth of the opium poppies in 3400 B.C. from the poppy plants (Papaver Somniferum). They were cultivated in lower Mesopotamia (Southeast Asia). It was referred to as the ‘Joy Plant.” Opium was passed down generations to reach the Egyptians. At this stage, the demand had risen significantly as the public figured out the power of the substance. Many other countries began to throw their hands into procedures to expand their availability and try to satisfy the demands. The cultivation spread across The Silk Road. The United Kingdom exported to China illegally against the will of the Chinese government. The Opium War was the result of China’s attempt to suppress the illegal trade of Opium. This led to widespread addiction in China. 


In 1806, German chemist Friedrich Wilhelm Adam Sertürner isolated a crystalline substance from opium, which he labeled “morphine” after the god of dreams, Morpheus. By the 1860s, substances like morphine were used to treat wounded soldiers. Morphine and other opioids have the power to reduce the level of physical distress noted with their pleasurable effects. 


Figure: The ascending and descending pain pathways 

Opioid receptors are expressed primarily in the cortex, limbic system, and brain stem. The three opioid receptors (receptor proteins); Mu, Delta, and Kappa are expressed in different numbers in most structures within the brain. The Mu receptor slows breathing, eliminates pain, and fills the mind with warm euphoria. 

Receptors are located at the synapse of neurons. Opioid receptors are distributed widely in the brain and found in the spinal cord and peripheral sensory and autonomic nerves. Typically, the messengers catch chemical messengers called neurotransmitters to activate the nerve cell. However, Opioid receptors do the opposite. They restrict electrical pulses to travel through the neurons. When opioids bind to opioid receptors, they promote potassium conductance which makes a neuron less likely to release an action potential (sending information through the axon away from the cell body). When the opioids bind to the opioid receptors, they inhibit calcium conductance which reduces the amount of neurotransmitters being released. 


Opioids are majorly used to acquire relief from pain. There is an ascending pathway, a descending pathway and the substantia gelatinosa. 

The ascending pathway is responsible for transmitting the pain signal up to the brain. For example, there has been a needle pierced into the right palm. Within the area of the injury, there would be immune cells residing. When these immune cells are damaged, they start to release cytokines chemicals just like any other cell would. Sensory nerve fibres exist all across the body and these sensory nerve fibres would respond to the cytokines chemicals and will carry the impulse to the dorsal horn of the spinal cord. Sensory nerve fibres are first order neurons. Within the spinal cord, the first order neuron will synapse with the second neuron to relay the signal. The second neuron will continue upwards through the spinal cord and the brainstem and will terminate in the thalamus of the brain which is in the somatosensory cortex. The somatosensory cortex is an area of the brain where sensation is perceived. In the thalamus, the second order neuron will then synapse with a third order neuron. The third order impulse will then relay the impulse to the region of the brain which addresses the body part. For example, since this impulse was generated in the right palm and thus the right hand, the impulse would be carried to the left side of the somatosensory cortex. The third order neuron helps recognize the area of injury. It is important to remember that the stimulus occurred on the right hand whilst the sensation is in the left side of the brain. The sensation is always on the opposite side of the brain to the stimulus. 


The descending pathway is essential in controlling and inhibiting the ascending pathway. Continuing with the same example, the neuron will go down through the brainstem and synapse with the second neuron. This second neuron is a serotonergic nor adrenergic neuron. This serotonergic nor adrenergic neuron will travel further down to the dorsal horn of the spinal cord. The role in summary of the serotonergic nor adrenergic neuron is to inhibit or control the communication between the first order and the second order neuron of the ascending pathway. The dorsal horn is an extremely important area. This particular area in the spinal cord can also be referred to as the substantia gelatinosa. 

In the substantia gelatinosa, for an overview of the ascending pathway, there is the first order neuron entering and synapsing with the second order neuron in the ascending pathway. The first order neuron will bring in an action potential which stimulates vesicles to release its content into the synaptic lift. The content is usually a substance. The substance stimulates the second order neuron and then the neuron will propagate an impulse up to the thalamus. Now, in the descending pathway, the serotonergic nor adrenergic neuron releases its contents which are serotonin and noradrenaline. These chemicals will conduct two tasks. Firstly, they will bind onto receptors of the presynaptic neuron and inhibit the release of the substance from the first order neuron. Secondly, they will stimulate a small neuron in the substantia gelatinosa called the interneuron. This interneuron is actually an opioid neuron which when stimulated, will release an endogenous opioid called enkephalin. Like all opioids, this opioid would inhibit the release of the substance from the first order neuron and also inhibit the postsynaptic neuron from depolarizing and thus stop the continuation of the impulse to the thalamus. Overall, all opioids will inhibit the ascending pathway and therefore reduce or restrict the sensation felt by the human body. 


Exposure to opioid drugs leads to tolerance, which therefore involves a decreased response to the drug and a need to consume more to provide for the same effect. This leads to addiction. The mechanism of the opioid tolerance isn't completely understood, but is thought to involve adaptive changes such as reduced number of functional receptors for the opioids to bind to. 


  1. Pain Relief

When hurt, for example, chronic back pain. The inflamed muscles are constantly sending pain signals to the brain via neurons in the spine. Opioid receptors restrict the pain signals, resulting in relief of pain. They are often used to manage severe pain caused by conditions like cancer, surgery, or trauma. Opioids are one of the most potent painkillers available. 

1. Mood Improvements

Sedation, Anxiety reduction and Euphoria as a few of the numerous mood improvements caused by opioid consumption. They can be a great help to people who are experiencing severe pain or depression.

2. Quick Onset

Opioids work quickly and can provide rapid pain relief. This allows for them to be useful in emergency situations. This makes them more useful when being compared to other forms of pain relieving methods when required in emergencies.


3. Multiple Forms

When compared to other pain relieving methods, opioids are more accessible as they come in many different forms, including pills, injections, patches and syrups. This makes them more adaptable in terms of dosing and administration. 


1. Addictive

Opioids are highly addictive, even for people who use them on prescriptions. It is not tough to develop a dependence on them. Long term use can further develop physical dependence, tolerance, and symptoms of withdrawal. 

2. Side Effects 

Opioids typically trigger constipation, nausea, drowsiness, vomiting and tweaking body temperatures. Once the opioids are evicted from a daily basis, a person with opioid dependence will have persistent diarrhoea, hot and cold sweats and goosebumps. 

3. Overdose Risk

Opioids are frequently misused, which can lead to overdose, addiction and other negative consequences. Opioids can also depress the respiratory system, and taking too much can lead to respiratory failure and death. 

 4. Interaction with other Drugs 

Opioids can interact with other drugs such as alcohol or sedatives which can increase the risk of respiratory depression and other serious side effects. 


In conclusion, opioids are powerful and pain-relieving and have been used as medication for decades. However, their highly addictive nature has led to millions of people worldwide suffering from addiction, overdose and death. Although modern technology and medical advancements in the future would generate better solutions to this pandemic, it is important to not lose sight of the full picture. The opioid crisis to potentially become more and more vicious taking the lives of many more. We must address this issue by primarily spreading awareness.

By Mohak Dugar 12J

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