Opioid receptors are proteins located throughout the central nervous system that play a critical role in regulating pain and reward, among other functions. The primary type of receptor that opioid drugs interact with is called the mu-opioid receptor. Their activation can lead not only to pain relief but also to respiratory depression.
This article will explain the key things you should know about opioid receptors, including their role in pain management, opioid dependence, and addiction.
What Are Opioid Receptors?
Opioid receptors are G protein-coupled receptors (GPCRs) that are primarily located on the outer membrane of nerve cells in the central nervous system (CNS). Besides the brain and spinal cord, these proteins are found in the gastrointestinal tract and white blood cells.
Part of the body’s endogenous opioid system, which regulates pain relief, mood, reward, stress response, and addictive behaviors, opioid receptors can be activated by:
- Endogenous opioids. These are opioid peptides the body naturally produces. Examples of endogenous opioids that bind to opioid receptors include endorphins, dynorphins, nociceptions/orphanins, endomorphins, and enkephalins.
- Exogenous opioids. These refer to the opioid drugs that interact with the same opioid receptors as endogenous opioids. In other words, rather than originating within the body, exogenous opioids are introduced to it orally, intravenously, or through other routes of administration.
Some examples of exogenous opioids include:
- Natural opioids (opiates) like morphine and codeine
- Semi-synthetic opioids, such as hydrocodone
- Synthetic opioids like fentanyl and methadone
Once activated, opioid receptors modulate brain function. The effects of opioids, be they endogenous or exogenous, are largely determined by the localization of opioid receptors within cell types and neurocircuits.
On this note, let’s explore the different types of opioid receptors.
4 Types of Opioid Receptors
The four main types of opioid receptors are mu, delta, kappa, and NOP receptors. Mu receptors are the main target for opioid pain medications, though some analgesics also act on other receptors.
Let’s take a closer look at each of these receptors and their effects:
#1. Mu (μ or MOP) Receptors
Mu receptors are located throughout the CNS, primarily in areas related to sensory and motor function. Their density is especially high in the cerebral cortex, caudate putamen, and amygdala, but they are also found in the dorsal horn of the spinal cord.
Mu receptors are primarily responsible for pain management, but their agonists, such as morphine, can also cause potentially life-threatening respiratory depression. These receptors also contribute to other side effects, such as constipation, euphoria, and sedation.
#2. Delta (δ or DOP) Receptors
Delta receptors are primarily located in the forebrain, though they are also found in hindbrain regions. The olfactory bulb, amygdala, neocortex, caudate putamen, and nucleus accumbens have the highest densities of these receptors. They also occur in the dorsal horn of the spinal cord, where they mediate the pain-relieving effects of δ agonists.
The role and function of delta opioid receptors haven’t been researched extensively yet. However, in addition to pain relief, these receptors may also regulate mood by producing anxiolytic effects. Like mu receptors, they may cause respiratory depression.
#3. Kappa (κ or KOP) Receptors
Kappa receptors are found on primary cells within the nucleus raphe magnus (NRM), which is a cluster of neurons located in the midbrain. These receptors differ from other opioid receptors in that they do not cause respiratory depression. Furthermore, the activation of kappa receptors is associated with dysphoria rather than euphoria, typical of mu receptor agonists.
Interestingly, researchers from the University of California found that κ–opioid analgesics, such as nalbuphine and butorphanol, produce significantly greater pain relief in women than in men.
#4. NOP Receptors
NOP receptors are primarily found on afferent nerve fibers. Currently, the only established endogenous ligand for these receptors is nociceptin/orphanin FQ (N/OFQ), which tends to induce analgesia at high doses and hyperalgesia at low doses. Opioid agonists and antagonists like naloxone and naltrexone show no significant affinity for this receptor.
According to McDonald and Lambert from Leicester Royal Infirmary, NOP receptor antagonists may be used as novel analgesics or taken in conjunction with traditional opioids to induce analgesic effects at lower doses in the future. However, the function of these receptors is still being researched.
Next, let’s learn more about opioid receptors and pain management.
Opioid Receptors and Pain Management
Opioid receptors play a pivotal role in pain management, as it is through these receptors that opioids exert their analgesic effects.
Put simply, opioids attach themselves to opioid receptors—primarily mu receptors—in the CNS, competing with endogenous opioids like endorphins to mediate pain relief. Opioids act on both afferent and efferent pain pathways, interfering with the transmission and perception of pain signals between the body and the brain by binding to opioid receptors. As a result, they dull the perception of pain, increasing the pain threshold.
While opioids are undeniably effective in controlling pain, taking them for a prolonged time leads to tolerance and physical dependence.
Repeated exposure to opioids fundamentally alters brain chemistry. It causes a decrease in the production of endogenous opioids and an increase in that of opioid receptors, leading to tolerance and dependence. Once you become dependent on opioids, your body won’t be able to function normally without them.
For this reason, these drugs are generally not recommended for chronic pain management. Paradoxically, long-term opioid use also increases the risk of opioid-induced hyperalgesia.
Ultimately, you should only take opioids if non-opioid pain medications cannot be used or aren’t effective enough. If you must take them, do so for a minimum time at the lowest dose possible to reduce the risk of opioid dependence. If left untreated, opioid dependence can develop into addiction.
Let’s learn more about the role of opioid receptors in opioid addiction.
The Role of Opioid Receptors in Opioid Addiction
The role of opioid receptors in opioid addiction development is closely linked to the effects of opioids on the brain’s reward system. Importantly, there’s a difference between opioid dependence and addiction, even though these terms are often used interchangeably.
Resulting from neurochemical changes, opioid dependence is purely physical; those dependent rely on opioids to maintain normal functioning. Opioid addiction, on the other hand, is largely psychological. It is marked by problematic, compulsive opioid use that persists despite negative consequences, be they job loss or strained relationships.
While pain relief is the primary effect of opioids, they can also cause rewarding effects upon binding to opioid receptors. This is because mu-receptor activation affects the brain’s reward centers, triggering a sudden surge of dopamine.
As a result, opioids induce intense euphoria that contributes to the addictive potential of these drugs. After all, people are naturally wired to repeat pleasurable behaviors. Because of this, it’s not rare for people taking prescription opioids to find themselves misusing these drugs eventually. Unfortunately, this puts them at a high risk of addiction.
More often than not, opioid addiction results from untreated opioid dependence. Therefore, it is critical to seek professional help as soon as you notice the first signs of physical dependence on opioids.
Signs and Symptoms of Opioid Dependence
The key signs and symptoms of opioid dependence are:
- Tolerance. Once people build up a tolerance to opioids, they have to increase their opioid intake to achieve the same effects as before.
- Opioid withdrawal symptoms. Opioid-dependent people suffer from physical and psychological symptoms upon drug discontinuation. Given that opioid withdrawals can be very uncomfortable and painful, it’s not uncommon for people to relapse or continue taking these medications, even when they no longer need them for medical reasons, just to feel normal.
If you’re looking for a safe and effective treatment for opioid addiction, ANR is your best option. Unlike traditional methods, this innovative treatment recognizes and addresses the neurobiological root of opioid dependence.
ANR Opioid Dependence Treatment
Accelerated Neuro-Regulation (ANR) is a revolutionary opioid dependence treatment that has helped nearly 25,000 patients worldwide achieve a long-lasting recovery.
Developed by Dr. Andre Waismann, ANR takes a medical, scientifically based approach to treating opioid dependence. It is the first and only method that addresses the neurobiological causes of dependence—the opioid-induced chemical imbalance—by resetting the opioid-receptor system to its original state.
As a comprehensive opioid dependence treatment, ANR achieves unparalleled results within a matter of days. Most patients return to their daily lives within days.
Benefits of Undergoing ANR Treatment
Some of the main benefits of undergoing ANR treatment include:
- Unmatched success rate. By modulating opioid receptors, ANR restores the nervous system to a pre-dependence state, eliminating dependence together with withdrawal symptoms. As such, this treatment negates the risk of relapse, which explains its exceptional success rate.
- Highest safety standards. ANR procedure is only conducted in an ICU setting of accredited hospitals by a team of highly experienced and compassionate board-certified medical professionals. Knowing this, you can rest assured you’ll be in good hands throughout the treatment.
- Personalized treatment. ANR offers a personalized approach by tailoring the treatment plan to each patient’s medical history and needs. Therefore, it is suitable for almost everyone, including those with comorbidities.
To learn more about ANR, contact us for a free, 100% confidential consultation. We’re here to help and guide you toward a happy and healthy life free of opioids and cravings.
Key Takeaways
We hope you found this article useful in learning about opioid receptors and their role in pain management, opioid dependence, and addiction.
Before you leave, let’s reiterate the key points we covered:
- Opioid receptors can be activated by endogenous opioids, such as endorphins, and exogenous opioids, like morphine.
- The four main types of opioid receptors are mu, delta, kappa, and NOP receptors.
- ANR is the only treatment that eradicates opioid dependence by addressing its root causes through opioid-receptor system modulation.
Opioid Receptors FAQ
Opioid receptors are responsible for mediating the effects of endogenous and exogenous opioids, such as endorphins (endogenous) or oxycodone (exogenous). Though they are primarily responsible for pain control, these receptors may also regulate mood, respiration, and other functions.
Opioids do not act on dopamine receptors directly. Dopamine and opioid receptors aren’t the same. Although opioids bind directly to opioid receptors, they also affect the brain’s reward system, causing sudden dopamine release. As a result, these drugs induce strong euphoric feelings, increasing the risk of abuse, dependence, and addiction.
Opioid receptors can heal after addiction. However, this can be a very lengthy and difficult process, which is why your best option is to undergo ANR. This comprehensive treatment restores balance in the opioid receptor system within a matter of days, facilitating long-lasting recovery with minimum discomfort.
ANR resets opioid receptors by decreasing the production of opioid receptors, blocking the additional receptors created while taking opioids until they atrophy, while allowing the body to restart proper endorphin production, thereby addressing the underlying neurochemical causes of opioid dependence. The procedure is done under sedation, meaning patients experience no discomfort from going through active opioid withdrawals.
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