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Why do different pain killers have different effects on people?


I've noticed some pain killers working great for me, while others have no effect.

Works for me

  • Aspirin
  • APC
  • Naproxen

Doesn't work for me

I doubt there is much of a placebo effect at work, since most of these either did or did not work when I first took them, without having expectations either way.

Whenever I have a head ache, I take an APC. I suspect it's actually the aspirin in there that does the job, since when I take just paracetamol, it doesn't do squat. As a kid I got children's aspirin, which worked.

I once had a severe back ache. I was prescribed diclofenac (a heavier variant than the over the counter one), which didn't work. I was then prescribed tramadol - same results. I then tried naproxen, which worked rightaway.

Why do some pain killers work while others don't?

Is there an underlying mechanism, that explains why some of these work while others don't? Does that predict if pain killers that I haven't used yet will work?

Please note that I'm not looking for medical advice on which pain killers to take; I'm just curious about how my body interacts with the various ones.


†: the one consisting of aspirin, paracetamol, and caffeine, not the one containing phenaticin. Think Excedrin.


I don't know of any interesting mechanism that is specific to pain killers, so I will instead answer for drugs in general.

Drug action is a complex process consisting of many steps. Let's take a simple example: A systemic direct inhibitor of a kinase. This drug would need to*:

  1. Be absorbed into your bloodstream
  2. Remain in your bloodstream for sufficient time
  3. Be absorbed into the tissue
  4. Be able to bind the target protein

1 can fail due to interaction with other concurrently taken drugs or food, or simply genetic factors affecting the particular functioning of the gut mucosa. 2 can fail because the kidneys are too good at eliminating it, or the liver is metabolizing it too agressively (both also subject to modulation by other drugs, foods and genetic factors). 3 can fail because the transports in the cells aren't working as rapidly, or represent an allele less likely to take in the drug, or are modulated by other drugs/foods. The tissue can also have efflux pumps or enzymes that break down the drug. 4 can fail because the drug was designed for a specific allele of that kinase, but you happen to have a different allele, which has a slightly different structure that is no longer targeted by this drug.

Then you have a host of physiological variables, and addiction/tolerance.

Apparently the most common genetic reason by far for variable drug sensitivity is the specific set of CYP genes you have. CYP enzymes are abundant in the liver and chemically process various molecules (including drugs).

Besides this, an interesting set of specific examples used to be available from 23andme. I'm not sure if they still provide this after the FDA ban on health information.

  • Clopidogrel sensitivity - CYP2C19 variation
  • Proton Pump Inhibitor (stomach acid reduction) - CYP2C19 variation
  • Abacavir (HIV drug) - HLA-B*5701 SNP
  • Acetaldehyde (alcohol flush) - ALDH2 mutation
  • 5-fluorouracil (chemotherapy) - DPYD mutation
  • PEG-IFN-alpha/RBV combination (Hepatitis C medicine) - IL28B SNP
  • Phenytoin (epilepsy drug) - CYP2C9 variants
  • Choline esters (class of muscle relaxants) - BCHE (CE degrader) variants
  • Sulfonylurea (used for type 2 diabetes) - CYP2C9 variants
  • Thiopurine (immune suppressant) - TPMT (enzyme that degrades thiopurine) variation
  • Warfarin (anticoagulant) - CYP2C9 variants
  • Caffeine - CYP1A2 SNP
  • Metformin (diabetes drug) - SNP rs11212617, near the ATM gene
  • Antidepressant - SNPs in ABCB1 affect likelihood of sexual dysfunction (common side effect)
  • Beta-Blocker (heart disease) - Mutations in ADRB1 which is normally blocked by the drug
  • Floxacillin (drug for staphylococcal infections) - SNPs in the MHC region affect liver toxicity of this drug
  • Heroin - OPRM1 receptor (target of heroin) SNPs affect efficacy
  • Lumiracoxib (used to treat pain and symptoms of osteoarthritis) - SNPs in the MHC region affect liver toxicity
  • Naltrexone (alcohol and narcotic addiction drug) - SNPs in OPRM1 affect how much it can reduce pleasurable feeling from narcotics
  • Statins (cardiovascular disease) - SNPs in COQ2 (mitochondrial component) affect risk of myopathy

As you can see, our friends the CYP family enzymes come up frequently, and some are even repeat offenders like CYP2C9. Besides that, there is a fair number of cases where variation in the specific target of the drug are relevant.

Note that this list is not comprehensive: Many drugs have not been studied in sufficient detail, and some may have complicated mechanisms instead of just "bind and inhibit protein X".

I have omitted many details and links to literature, I am sure you can easily find them by searching on Google Scholar with the keywords I already gave. Let me know if that doesn't work, though.


*: Note that these aren't necessarily required for all drugs. For example, some drugs can be applied directly to the skin and hence do not need to pass through blood.


Short answer: different people have different amount of active receptors. In treatment, combination scores of Pharmacodynamics and Pharmacokinetics determine the final effect of the drug. Receptors determine many effects of the drug in many pathways. Different people also sense pains differently (Psychology).

Review answer

The purpose of treatment is to relieve pain and maintain function. Your question is biased. You cannot only concentrate on painkilling in maintaining health. These both are the reasons for the complains of the patient, not only the pain.

For instance, in rheumatoid arthritis, response to therapy can be quantitated using many measures including American College of Rheumatology system values ACR20, ACR50 and ACR70, which denotes the percentage of patients showing an improvement of 20%, 50% or 70% in a global assessment of signs (maintaining function) and symptoms (pains).

Each patient has own health, different from one another. Our body adapts to the environment and individual conditions of the body to maintain homeostasis. Receptors adapt for instance. They can be active or inactive - in short-run and long-run - again depending on the conditions at hand.

Painkillers i.e. analgesics have different properties:

  • anti-inflammatory effect - acute and chronic conditions (inflammation is the major mechanism under many pathologies) e.g. nonsteiroidal anti-inflammatory drugs (NSAIDs, please, see this answer about the particular mechanisms and how different people have different effects from NSAID painkillers) and glucocorticoids (most)
  • symptoms relieving specific drugs e.g. disease-modifying antirheumatic drugs (DMARDs)
  • anti-platelet effect - e.g. the older you get, the more platelets stick together.
  • anti-pyretic effect

which all can be toxic. Note that many drugs alone or/and as combination can work as painkillers i.e. pain relievers. Aspirin for instance has both anti-inflammatory and anti-platelet properties. However, it is rarely anymore used as anti-inflammatory. The anti-platelet property is dependent on the exact dosage of the administration. Aspirin's mechanism of action is to inhibit platelet COX which antiplatelet effect lasts 8-10 days (life of the platelet). In other tissues, synthesis of new COX replaces the inactivated enzyme so that ordinary doses have a duration of 6-12 hours. Please, review any Pharmacology -textbook for more info about aspirin.

Each these drug has own Pharmacodynamics and Pharmacokinetics

  • Pharmacodynamics answers to the question What drug does to the body? It stimulates some receptors, activates some pathways,…
  • Pharmacokinetics - What does body do to the drug? It metabolises it (enzymes, receptors). It distributes it. It excretes it (kidneys, feaces).

In treatment, you consider what is the target organ. You need to think what is causing the dysfunction and the pain. You try to restore the function and relieve pain. The component of drug needs to reach the target tissue e.g. your pancreas' beta cells do no produce insulin so your blood glucose is high. Complications of this are polyuria and eventually exodus if untreated. Insulin is injected into the fatty tissue. We do not have long-term acting insulin administered orally - our metabolism start to break the drug so it does not have wanted treatment. If insulin administered to the muscle, the time of action is too times less, again because muscle is metabolising the insulin i.e. a chain of peptides (protein).

No all symptoms and diseases have painkillers. For instance, prehemorrhoid and some types of itching related to posthemorrhoids. However, for both, there are some special salvas for proplylaxis but they are not complete.

Now, you can start to read something in SuperBest's answer about host's physiological variables and addiction/tolerance which alters the mechanisms (receptors) of pathways in Pharmacodynamics and Pharmacokinetics.

Sources

  1. Basic and Clinical Pharmacology, 11th edition, 2009, Bertram Katzung.
  2. My notes in Pharmacology classes during 2014.

Sex Differences in Opioid Analgesia: A Complicated Picture

Catherine Offord
Jan 1, 2018

ANDRZEJ KRAUZE

G raduate student Anne Murphy had run out of rats. Or rather, she&rsquod run out of male rats, the animals she was using to study brain regions involved in pain modulation for her PhD at the University of Cincinnati in the early 1990s. At a time when neuroscientists almost exclusively used male animals for research, what Murphy did next was unusual: she used a female rat instead.

&ldquoI had the hardest time to get the female to go under the anesthesia she wasn&rsquot acting right,&rdquo Murphy says. Her advisor&rsquos explanation? &ldquo&lsquoWell, you know those females, they have hormones, and those hormones are always fluctuating and they&rsquore so variable,&rsquo&rdquo Murphy recalls. The comments struck a nerve. &ldquoIt really got to me,&rdquo she says. &ldquoI&rsquom a female. I have hormones that fluctuate. . . . It made me determined to investigate the differences between males and females in terms of.

Her decision was timely. Since the ’90s, evidence has been accumulating to suggest that not only do women experience a higher incidence of chronic pain syndromes than men do—fibromyalgia and interstitial cystitis, for example—females also generally report higher pain intensities. Additionally, Murphy notes, a handful of clinical studies has suggested that women require higher doses of opioid pain medications such as morphine for comparable analgesia plus, they experience worse side effects and a higher risk of addiction.

Although the explanations for sex differences in pain are still a topic of considerable scientific uncertainty, Murphy, now a professor at Georgia State University, has been working with her lab to clarify the picture by teasing out some of the neurological mechanisms underlying pain’s alleviation. As part of this work, one of Murphy’s graduate students, Hillary Doyle, recently carried out a project to look for predictors of morphine’s effectiveness in healthy rats in a brain region called the periaqueductal gray (PAG)—a key pain-response control center. In the PAG, as in many other parts of the body, morphine binds to μ opioid receptors and triggers signaling pathways to kill pain. Studies have shown that female rodents receiving the drug via direct PAG injection need at least 10 times more morphine than males do in order to achieve comparable levels of analgesia.

Ultimately, these studies could point the way to developing more-specific and targeted pharmacotherapies. —Alan Gintzler
State University of New York
Downstate Medical Center

But previous work by Murphy’s lab and others suggested that morphine can also act through another mechanism in the PAG by binding to protein receptors expressed on microglia—specialized immune cells implicated in neuropathic pain (see "Glial Ties to Persistent Pain"). This binding triggers inflammatory pathways that, paradoxically, work against the drug’s analgesic effects. If females possessed higher microglia densities, Murphy and Doyle hypothesized, then their brains might be more susceptible to the inflammatory effects of morphine and less responsive to the drug’s intended analgesia.

When the researchers looked, however, they found that male and female rats showed similar densities of microglia in the PAG. But studying the cells themselves, Doyle identified a different sort of variation. Microglia in different states of activation look different under the microscope, she tells The Scientist. Resting microglia have what’s called a “ramified” structure, where arm-like processes extend from the cell body activated microglia, by contrast, have a round, amoeboid structure. “We see a much greater percentage of active-type microglia in females than in males,” says Doyle, now a medical associate at the Scienomics Group, a health and science communications consulting company. “These were changes specific to regions involved in pain, like the PAG.”

Sex differences in morphine responsiveness, then, might result partly from fundamental differences in baseline microglial activity, not density. Sure enough, Murphy’s team found that the percentage of microglia in an active state in a rat’s PAG correlated with the amount of morphine needed to render the animal indifferent to a thermally painful light beam aimed at a hind paw. What’s more, when the researchers administered drugs to block the inflammatory pathways triggered by microglia, they found that sex differences in these responses disappeared: females no longer needed substantially higher doses for the same analgesic effect (J Neurosci, 37:3202-14, 2017).

“It’s a beautiful example of mechanisms differing in males and females,” says Alan Gintzler, a biochemist and neurobiologist at the State University of New York Downstate Medical Center who was not involved with the work. His own lab has also been documenting sex differences in pain, in particular, in the spinal cord. For example, the group has found that female rats require combined activation of both μ and Κ opioid receptors in their spinal cords for morphine analgesia, and often express the proteins as a single complex males, by contrast, require only μ activation and show much lower levels of the heterodimer (PNAS, 107:20115-19, 2010).

The hope, Murphy notes, is that one day, with enhanced understanding of the biology of pain in both sexes, researchers might design better drugs to specifically target pathways that induce analgesia. Her group is currently working on compounds that could effectively block microglia activation, for example. “Ultimately, [these studies] could point the way to developing more-specific and targeted pharmacotherapies,” Gintzler says. Such therapies would “target certain pathways, or certain cells, that are more active in males or females—rather than bathing the entire nervous system in a narcotic.”

But Gintzler also notes that the backdrop to such work is highly complicated. For one thing, researchers are divided on whether women really do need more morphine than men do—some studies suggest they require less, or about the same amount—clouding the human relevance of the Georgia State team’s most recent findings in rats. For another, researchers have proposed alternative explanations for sex differences in human pain processing and alleviation that have no obvious links with the PAG. One famous study, published in the early 2000s, found that after taking into account people’s “gender role expectations”—beliefs about whether men should express feeling pain, for example—once-significant sex differences in pain threshold disappeared (Pain, 96:335-42, 2002).

Although there are important differences in the way such studies are carried out—in rodents or humans, in models of chronic or acute pain, in studies of pain sensitivity or pain alleviation—this tangle of vying explanations for sex differences in pain research points to a larger confusion in the field, says Jeffrey Mogil, a neuroscientist at McGill University. “You would imagine that [each of these theories] would take a little chunk out of the sex difference and reduce it somewhat,” he says. “But that’s not what all these studies show. . . . They’re all ‘complete’ explanations.”

Of course, it’s conceivable, Mogil adds, that multiple factors—spanning the range from molecular biology to culture—act in series, in which case blocking any one factor could substantially reduce sex differences in humans’ pain experiences. For now, though, he suggests that the most important finding from studies like Murphy’s is simply that qualitative differences exist and warrant further study.

“It doesn’t matter what direction the sex differences go in and how they’re resolved,” Mogil says. “This is a wonky scientific question that scientists will figure out eventually. The bigger picture is: there are sex differences here, and no one would have seen them if they weren’t [conducting research with] both sexes.”


What does pain do?

Pain motivates us to act. Think about that hot pan again. Now imagine you’d picked up the pan before realising it was too hot to handle. Your options are to drop it and make a mess, or bear the pain until a solution is found.

In an instant, you detect that the pan is hot (thermal), it’s on your hand (location), it’s painful (intensity), you don’t like it (unpleasant), it’s engaged your full attention (cognition), and you’re not happy about it (emotional). That’s a lot of things, which is why pain is often called a ‘multidimensional’ experience.

So, what do you do? Well, from past experiences, learnt responses, and potential outcomes (like being told off for dropping the pan) you make a decision and act. Recruiting extraordinary brain-based networks, you are able to block the pain and get the hot pan to safety – then it’s back to that cold tap.

Pain drives action, prompting us to run away, avoid it in the first place, or signal to others that we need help and relief.


Other treatments and activities that don’t help

Bed rest is not helpful for back pain, and might even slow recovery. However heavy physical work should also be avoided in the first few days after a back pain episode starts.

Other treatment options – including acupuncture, ultrasound, electrical nerve simulation, and corsets or foot orthotics – are not recommended, since there is no strong evidence supporting their use.

Even if the cause of back pain is unknown, imaging (x-rays, MRI) is unlikely to influence management or provide meaningful information.


List of Strong Painkillers with Reviews

General Guideline

  • Pain killers which are NSAIDs (nonsteroidal anti-inflammatory drugs) works on the patho-physiological processes that elicit pain, fever and other signs of swelling in the body.
  • Corticosteroids pain reliever are usually given for the management of musculoskeletal injuries due to its effect on shutting down inflammation causing processes.
  • The pain which is set off by any damaged or sensitive nerves (see most commonly in cases like sciatica or shingles) is generally handled by nerve blockers or anti-depressants. These tablets have the capacity to regulate the understanding of pain by main worried system.
  • Some pain- killers are made use of as muscle relaxants to decreases the intensity of pain triggered by the muscles group. This pain reliever serve as sedative for main worried system.
  • Factor behind consuming medication is to enhance the lifestyle. It is essential to recognize that every pain reliever is connected with some negative effects in short term or long term. Therefore it is encouraged to learn and determine potential drawbacks prior to taking in any painkiller.

Following are the description of a strong and effective pain relievers:

Paracetamol

It is among the popular pain killers readily available (primarily utilized for the management of common headaches and non nerve discomforts). The efficient dosage is 2 tablets which can be consumed a minimum of 4 times a day (or at every 6 hrs interval). This dose and dosing routine is thought about safe for grownups. There are no common adverse effects for this medication and this drug can be used for longer time period. Nevertheless overdose of paracetamol can trigger some serious negative effects for that reason it is highly recommended not to increase the dosage if the intensity of pain increases. If pain symptoms cannot resolve within 3 days, get in touch with the basic physician.

This drug is a type of NSAIDs i.e. non steroidal anti inflammatory drugs. It works best on inflammation triggering drugs in a very same method it is used for dealing with arthritis or any injury. This drug is not enabled to be made use of for longer time periods unless the swelling does not vanish. If this drug is consumed for longer time periods, it can result in significant adverse effects like bleeding, indigestion, heart problems and kidney issues. It is highly encouraged not to take in overdose of this drug as it can trigger severe repercussions.

Some painkillers offer quick relief that lasts for a short time. These are called short-acting pain relievers. Long-acting painkillers (also called slow-release painkillers) are slower to control the pain but work for a longer time.

This drug does not work well alone but can provide far much better results when used with paracetamol in a single formulation. Over the counter drugs are available under the label of co-codamol (which is paracetamol integrated with lower amount of codeine). Greater potency of codeine should just be utilized on doctor’s prescription. Some other painkillers with greater potency consist of Zydol (tramadol) and dihydrocodeine.

Drugs under this category are considered as habit-forming or addicting. The factor behind is these drugs makes an individual feel unhealthy for a short time duration when stop taking in. If for any certain factor this drug is consumed for longer period then consult your basic doctor for suggestions.

Amitriptyline and Gabapentin

Gabapentin is the drug used for dealing with epilepsy and amitriptyline medication and is used for dealing with anxiety. Both of the drugs are also given to patients for dealing with pain activated by damaged or hyper-sensitive nerves that includes sciatica, shingles or nerve pain caused by diabetes. This medication is taken in when prescribed by the general doctor. Adverse effects of both the drugs consist of dizziness and drowsiness.

This drug is thought about as effective and best pain reliever offered. Some other drugs fall under this classification consist of fentanyl, buprenorphine and Oxycodone. It is encouraged to book using this pain killer just in severe pain. These medications are only consumed when recommended by pain professional or general physician as the doctor will keep an eye on the development on dosage potency. These drugs are typically used for long term to administer the pain.

Strong opioids are medicines used to deal with severe or long-lasting (persistent) pain. Although there are numerous kinds of strong opioids, morphine is the most frequently utilized strong opioid and usually the first one your doctor will prescribe, according iytmed.com.

Oxymorphone hydrochloride extended-release tablets are suggested for the management of pain severe sufficient to require daily, ongoing, long-term opioid treatment and for which alternative treatment choices are insufficient.

The most typical side-effects are constipation, feeling sick (queasiness), and tiredness. It is uncommon for individuals who take a strong opioid to deal with pain to become addicted to strong opioids.

The opioids deal with specific opioid receptors in the body, which are mainly located in the brain and the spine. Lots of oral opioids are used in the treatment of chronic pain. Integrating opioids with other painkillers such as paracetamol and NSAIDs involves assaulting the pain on various receptors. This typically reduces your opioid requirements by approximately 30%, which leads to improved pain relief and a lowered risk of adverse effects.

The following table lists more OTC and recommended painkillers:


Interviewer: Your painkillers don't work for you anymore. Is this normal? We'll find out next on The Scope.

We're talking today with Dr. Kirtly Parker Jones. She's the expert on all things woman. Dr. Kirtly Jones, a lot of women have been emailing us lately for various reasons of pain and they've been saying that painkillers just don't work for them anymore. Is this normal? Can you grow a tolerance to painkillers?

Dr. Jones: This is a great question and, in fact, yes, this is normal. Now, let's talk a bit about what we're talking about painkillers here. I'm assuming our questioners are asking about narcotics.

Interviewer: Let's assume yes.

Dr. Jones: So we'll make that assumption. What we do know is that narcotics are opioids and these would be drugs like hydrocodone, and oxycodone, and morphine, Demerol, drugs like that, are actually pretty good for acute pain, meaning they work when the pain is acute onset. Let's say you just had surgery or you just had a cesarean section, it can be really great for a couple days. However, two things happen if you take it for longer than a week or so. Number one, we have very good evidence that narcotics do not work for chronic pain.

Interviewer: Doesn't do them any good.

Dr. Jones: Doesn't do them any good. For two reasons. Number one, it doesn't work for chronic pain and, in fact, narcotics can sensitize people to pain so they actually feel more pain.

Interviewer: So now, what classifies as chronic pain to you?

Dr. Jones: Well, chronic pain is pain that goes on longer for a week or two.

Dr. Jones: So that's chronic pain. So acute pain, we've all had it. You break your leg, you sprain your ankle, you've just got an abscess in your finger or you just had an operation.

Interviewer: Something that's going to go away.

Dr. Jones: Something that's going to go away cause you're going to heal.

Dr. Jones: But during that going away time, narcotics can be very useful.

Interviewer: Like a toothache. My dentist gives me painkillers when I go and have my wisdom tooth taken out.

Dr. Jones: Yeah, right. So that's a good thing because it's going to hurt for a couple days and narcotics work for that. But over time, narcotics don't work. Now, let's talk about those two reasons. One is that narcotics can actually sensitize you to pain so you feel it more.

So the other issue is that when you've taken narcotics for a while, the same dose doesn't give you the same effect. So that's where you get used to the narcotic effect. What then happens is that people start taking more narcotics and then you get into this vicious circle of taking more narcotics and then it not working as well and then maybe sensitizing you to pain so your pain actually feels more. So you take more narcotics and then the difficulty is are you really needing those narcotics or are you addicted? What is the behavior around getting those?

So more and more, we've understood that chronic pain . . . now, there is a kind of chronic pain, meaning longer than a couple weeks, in which narcotics can be very helpful and that's the pain associated with cancer. So cancer pain tends to come and it gets worse and worse as the cancer spreads. So in reality, it's almost like acute pain that keeps happening over and over as the cancer spreads to a new area.

So the goal for pain is that acute pain should be treated with the least amount of drugs that does the job well for someone so that they can get up and move around. We never can make all the pain go away for someone, we'll say, after surgery. So our goal is to make it tolerable for people to get up and move around because getting up and moving around is really important to make the pain feel less. So moving is important for most kinds of pain to make you feel better.

If our listeners ask, "My painkiller isn't working as well as it used to," then the answer is right, how long have you been taking it and what have you been taking it for?

Particularly for things that are chronic like low back pain, or people who have pelvic pain that's chronic, not just like the acute pain that comes with a bad period or with an ovarian cyst that ruptures or something like that. So people who use pain on an everyday basis, their pain medicines are not going to work as well and they're going to need more and they might become addicted and it doesn't work for chronic pain in the first place.

So what are you supposed to do? If your pain pills aren't doing for you what you want, should you get a higher dose? Should you get a stronger narcotic? I think most pain specialists would say this is the time for a reevaluation of your pain and looking at other options for pain management.

So other options at pain management actually include cognitive behavioral therapy. In other words, helping you deal with how you appreciate that pain, how you respond to that pain. Exercise can be helpful. Physiotherapy can be helpful. Yoga can be helpful. Mindfulness therapy can be helpful. But we really need to take another approach to people with chronic pain than giving people narcotics because the consequences of giving people narcotics for chronic pain have led to essentially a rise in the rate of deaths of young people and middle-aged people in this country.

We now see an actual drop in the lifespan in this country, probably related to suicides and narcotic overdoses, which is a pretty sad thing. So if you have chronic pain, it's not about narcotics, it's about other therapies. If you have acute pain, that tooth, go to your dentist and you can take it for a couple days, but be careful about taking it for longer.

updated: January 3, 2019
originally published: June 2, 2016

For Patients

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Effects on the Baby

Like most things the mother consumes, painkillers, especially the stronger ones, also can have an effect on the unborn child.

Among the effects believed to happen to the baby are the following:

  • Heart disease. When a mother takes ibuprofen during pregnancy, she may have to deal with the possibility of her unborn child developing heart disease or, for boys, fertility problem. This may be due to low levels of amniotic fluid inside the womb due to consequent high blood pressure in the fetus’ lungs.
  • Congenital diseases. As the baby develops inside the mother’s womb, taking painkillers—particularly the prescription ones or opioids—might not be a good option. The unborn baby can develop a congenital disease, such as spina bifida (an abnormality in the spine), hydrocephaly (the presence of too much liquid in the baby’s brain), and even glaucoma (when too much pressure in the eye causes loss of sight).
  • Future fertility. Not the mother's fertility, but the child's. One study linked the use of painkillers—such as the commonly used paracetamol and ibuprofen—during pregnancy to fertility issues for the baby later in life by reducing the number of sperm and egg cells.
  • Neonatal Abstinence Syndrome . When the mother has used strong painkillers or opioids, the baby sometimes suffers from Neonatal Abstinence Syndrome (NAS), basically withdrawal symptoms because the baby has become dependent on the drug.

In addition to the effects on the baby, long-term painkillers abuse may result in severe negative consequences for the mother: respiratory depression, coma, or even death. That's a high price to pay for pain relief.


Even when pain medications are prescribed for legitimate reasons, it is important that you remain aware of the addictive potential certain pain relievers have. If you are concerned about any medication that you have been prescribed, talk to your doctor or pharmacist.

If you or a loved one are struggling with substance use or addiction, contact the Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-4357 for information on support and treatment facilities in your area.


What Is the Relationship between Neurotransmitters and Pain?

Neurotransmitters are chemicals in the nervous system that help to pass information between neurons. Some neurotransmitters are responsible for the transmission of pain signals, while others help to block pain. Researchers are investigating the relationship between various types of neurotransmitters and pain in hopes of creating new treatments for chronic pain.

Messages are sent through the nervous system by means of electrical and chemical signals. Electrical signals pass through the nerves themselves, but nerves are separated from one another by small gaps, known as synapses, through which the electrical signals cannot pass. At the end of a nerve cell, these signals are converted to chemical signals in the form of neurotransmitters, which pass the message across the synapse to the next nerve cell.

Some of the most important messages sent through the nervous system are messages relating to pain. Pain signals the body that something is wrong and that the person feeling pain should take action to correct it, such as by removing one's hand from a hot stove. The various neurons, neurotransmitters and pain responses work together to prevent unnecessary damage to the body.

When pain becomes unmanageable, however, most people will turn to painkillers. Over-the-counter painkillers, such as acetaminophen or ibuprofen, work by blocking the enzyme known as cyclooxygenase (COX) rather than by directly effecting neurotransmitters. These over-the-counter medicines should not usually be taken over an extended period of time, as they tend to lose efficacy the longer they are taken.

To provide stronger pain relief, many doctors will recommend treatments that exploit the relationship between neurotransmitters and pain. The neurotransmitter serotonin, for instance, is usually associated with mood, as serotonin deficiencies often lead to depression. One of its lesser-known functions, however, is to block excess pain signals. For this reason, antidepressants in the Selective Serotonin Re-uptake Inhibitor (SSRI) class of drugs may also be used to treat chronic pain.

Endorphins are another connection between neurotransmitters and pain. This natural painkiller functions in a way that is closely related to morphine. Endorphins, however, are produced primarily through exercise. A steady regimen of exercise may therefore help manage pain better than many other drugs.


It’s been found that redheads require approximately 19% more anaesthesia than other hair colours during surgery. This is also applicable to novocaine-type drugs often used by dentists, which is a good reason for redheads being more afraid of having dental work.

However, despite this doom and gloom, natural gingers are believed to be a little more hardcore when it comes to opioid types of painkillers, such as codeine or fentanyl, which are generally available via prescription.

This extra resilience to pain is thanks to our MC1R gene, as redheads’ brains are able to release a hormone that mimics endorphins, giving us a little self-painkilling boost. This means that in theory redheads can have the same effects of pain relief from using a smaller dosage.