Medications for Pain

What is Acetaminophen?

Acetaminophen is a non-addictive drug that can be used to treat mild to moderate pain and fever. Acetaminophen is commonly used to treat headache, arthritis and back pain, tooth pain, the common cold, sore throat, sinus infection, bites, stings, and sprains. Acetaminophen is available over the counter in the U.S. or at higher strengths by prescription.

How does Acetaminophen work?

Like NSAIDs (see NSAID section), acetaminophen inhibits the production of prostaglandins in the body which promote fever. Unlike NSAIDs, acetaminophen is not a potent inhibitor of COX-1 or COX-2 and only has limited anti-inflammatory effects. Thus, acetaminophen is a potent fever reducer and appears to raise the threshold for pain making it harder for nociceptive information to be interpreted as pain by the brain.

What are the names of some Acetaminophen products?

• Acetaminophen (e.g., Tylenol, Paracetamol, Panadol)

Common Brands that combine Acetaminophen with other drugs

• Acetaminophen + aspirin + caffeine (e.g., Excedrin)

Risks

Taking more than 4 grams of acetaminophen every day can damage your liver. This is the reason why it's not recommended to take more than that dose. If you already have liver disease, you should not take more than 2 grams of acetaminophen every day as it increases your risk of liver failure.

What are NSAIDS?

Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs with little to no risk of addiction, that can help to reduce pain, inflammation, and fever.

NSAIDs are commonly used to manage arthritis, headaches, sports injuries, and menstrual cramps. NSAIDs are available over the counter in the U.S. or at higher strengths by prescription.

How do NSAIDs work?

The body produces enzymes called cyclooxygenases (COX) which in turn produce prostaglandins. There are two types of COX enzymes (COX-1 and COX-2). Both produce prostaglandins that promote inflammation and fever. While inflammation and fever are unpleasant, these symptoms are also important for healing. In addition, COX-1 produces prostaglandins that also play a role in blood clotting and protecting the lining of the stomach from acid damage.

NSAIDs reduce pain by blocking the COX enzymes throughout the body leading to reductions in inflammation and fever. Unfortunately, blocked COX-1 enzymes can also result in thinner blood (e.g., reduced ability to clot), and unprotected stomach linings (e.g., ulcers and stomach bleeding).

While traditional NSAIDs blocked both COX-1 and COX-2 enzymes, newer NSAIDs called "COX-2 inhibitors" only block the COX-2 enzyme so that inflammation and fever can be reduced without effecting blood clotting and the stomach lining.

What are the names of some NSAIDs?

Traditional NSAIDs

• Aspirin
• Ibuprofen (e.g., Motrin, Advil)
• Naproxen (e.g., Naprosyn, Aleve, Anaprox, Naprelan)
• Oxaprozin (e.g., Daypro)
• Diclofenac (e.g., Cambia, Cataflam, Voltaren-XR, Zipsor, Zorvolex)
• Piroxicam (e.g., Feldene)

COX-2 Inhibitors

• Celecoxib (e.g., Celebrex)

Risks

Short-term side effects of NSAIDS include:

• Nausea
• Stomach pain
• Gastrointestinal bleeding and ulcers

Some of the long-term risks of NSAID use include:

• Interactions with drugs used to treat heart disease such as blood thinners and antihypertensive drugs
• Large doses confer risks of kidney problems
• Fluid retention
• High blood pressure
• Increased risk of cardiovascular problems for COX-2 inhibitors

Talk to your doctor before using NSAIDs, especially if you are pregnant, have high blood pressure, asthma, or a history of kidney or liver disease. Side effects tend to be greater in older individuals.

What are Opioids?

Narcotic analgesics (also known as opioids) are used to treat moderate to severe pain. Most individuals take opioids for short periods of time, mostly for nociceptive forms of pain (e.g., acute pain). Opioids have been used to treat pain associated with cancer, terminal illness, severe injury, and post-surgical pain. There is less evidence that opioids are effective in treating chronic non-cancerous forms of pain (e.g., chronic pancreatitis, low back pain, headache, arthritis) even though these forms of chronic pain can be quite intense. Opioids require a prescription, and a physician must have a special license for them.

How do Opioids work?

While the exact mechanism of action for these drugs is still unknown, we do have some idea about how they work.

Opioids cause the brain to release a chemical called dopamine. Dopamine regulates the brain's reward system and influences movement, emotion, thinking, motivation, and feelings of pleasure and calm. It also raises the threshold for pain by making it harder for nociceptive information to be interpreted as pain by the brain. Overstimulation of this reward system is associated with feelings of euphoria and slow breathing. Over time, more and more of the drug may be needed to get the same pain reducing effects.

What are the names of some Opioid analgesics?

• Codeine
• Tramadol (e.g., Ultram, Ultracet, ConZip) – this grouping represents a hybrid class of analgesic
• Hydrocodone (e.g., Zohydro ER, Vicodin, Lortab)
• Oxycodone (e.g., OxyContin, Roxicodone, Percocet)
• Hydromorphone (e.g., Dilaudid, Exalgo)
• Morphine (e.g., Avinza, Kadian, MSIR, MS Contin)
• Fentanyl (e.g., Actiq, Duragesic Sublimaze)
• Oxymorphone (e.g., Opana)
• Meperidine (e.g., Demerol)
• Methadone (e.g., Methadose, Diskets, Dolophine)

Risks

• Side effects: The side effects of narcotic analgesics can include the following: dry mouth, itching, headache, dizziness, constipation, sedation, vomiting, chest and abdominal pain, nausea, fatigue, unclear thinking, headache, trouble breathing, mood changes, abnormal heart beats, sexual dysfunction, cardiac arrest, addiction, and death. Narcotic analgesics also interfere with productive functioning such as driving a car, operating machinery, and performing many work-related tasks. Sometimes opioids can also modify the central nervous system such that the perception of pain actually gets amplified rather than reduced.
• Addiction: Opioids can be highly addictive which can lead to misuse and abuse. Addiction is characterized by overwhelming cravings for the drug, compulsive use of the drug, and continued use of the drug even after evidence of harm to one's self or others being associated with the use. Addiction to opioids has been associated with an increased risk of death, overdose, infections, heart infections, narcotic bowel syndrome.
• Opioid overdose: it is a medical emergency that occurs when someone takes too much of an opioid, slowing or stopping their breathing. It can be fatal, especially with synthetic opioids like illegally made fentanyl, which are involved in most overdose deaths today. Warning signs include unconsciousness, slow or shallow breathing, and blue lips or fingernails. Overdoses are preventable. Safe prescribing, avoiding illegal pills, using fentanyl test strips, and treating opioid use disorder are key strategies for prevention. Naloxone (Narcan) is a medication that can quickly reverse opioid effects and save lives if given promptly. If you have not received a naloxone prescription along with your opioid medication, ask your doctor if you need it.

Are you trying to decrease your opioid use?

If reducing the use of narcotic analgesics is desired, it is recommended that you consult with your healthcare provider. Usually, the taper will involve a slow controlled reduction in the amount and frequency of drug use. Ideally you and your provider will work together in making the taper a success.

What to do if you think you have an opioid addiction?

If you think you have an opioid addiction, it's important to seek medical attention as this is a medical condition. Your doctor can assess your situation and recommend safe, effective treatment options such as:

• Medication-Assisted Treatment: Includes buprenorphine, methadone, or naltrexone to reduce cravings and withdrawal.
• Behavioral therapy and counseling: Helps you understand and manage addiction triggers.
• Support groups: Narcotics Anonymous or SMART Recovery.

Do not stop opioids abruptly without medical advice, this can lead to severe withdrawal symptoms. Recovery is possible with the right support.

How to find help for opioid addiction?

SAMHSA's National Helpline, 1-800-662-HELP (4357) (also known as the Treatment Referral Routing Service), or TTY: 1-800-487-4889 is a confidential, free, 24-hour-a-day, 365-day-a-year, information service, in English and Spanish, for individuals and family members facing mental and/or substance use disorders. This service provides referrals to local treatment facilities, support groups, and community-based organizations.

Also visit the online treatment locator, or send your zip code via text message: 435748 (HELP4U) to find help near you.

What are gabapentinoids?

Two drugs, gabapentin and pregabalin, that were originally shown to be effective in treating seizures, were subsequently shown to be helpful for treating some types of chronic pain. These drugs are approved in the US for treatment of neuropathic pain and fibromyalgia, but are more widely used to treat other types of chronic pain, and even acute pain (for example, in the period following surgery).

How do gabapentinoids work?

Gabapentinoids are known to bind to a specific receptor in the body, the alpha-2-delta calcium channel receptor. When the drug binds to these receptors, it reduces the excitability of the nervous system. Hyperexcitability of the nervous system is thought to contribute to many types of pain. The excitability-reducing effects of these drugs may occur in several areas of the nervous system (e.g. nerves, spinal cord, brain).

What are the names of some gabapentinoids?

• Pregabalin (Lyrica) has shown to be beneficial in patients with painful chronic pancreatitis, particularly when neuropathic mechanisms are involved. Pregabalin may help reduce both pain intensity and the need for opioid use.
• Gabapentin (Neurontin)

Risks

Some short-term side effects of these drugs include:

• Drowsiness
• Dizziness
• Swelling of hands and feet
• Trouble concentrating
• Increased appetite
• Weight gain
• Dry mouth
• Blurred vision

Less common side effects include:

• A severe allergic reaction with hives or skin blisters, trouble breathing, or swelling in the face, mouth, or throat can occur. Talk to your doctor about if this occurs.
• Some people have thoughts about suicide while taking these drugs. Talk to your doctor if you notice this.
• People can become addicted to these drugs. However, they are not as addictive as many other classes of drugs such as opioids.

What are Antidepressants?

Several drugs that were originally shown to be effective in treating depression can also be used to treat chronic pain. Not all antidepressants work to treat pain, and when antidepressants do work to treat pain, it is not because they are treating depression. Individuals with chronic pain without depression are just as likely to experience an improvement in pain when they are given these drugs as are individuals with both depression and chronic pain.

In addition to chronic pain, these drugs can also be used to treat depression and anxiety.

How do Antidepressants work?

The antidepressants that are most useful in treating chronic pain are those that raise levels of two different brain chemicals or neurotransmitters – serotonin and norepinephrine. Antidepressants that mainly increase serotonin are called Selective Serotonin Reuptake Inhibitors (SSRIs) whereas the antidepressants that increase both serotonin and norepinephrine are called Serotonin Norepinephrine Reuptake Inhibitors (SNRIs). The latter SNRI drugs that increase both serotonin and norepinephrine are often better at treating pain than the SSRI drugs that only increase serotonin.

The reason that these drugs can be used to treat pain is that serotonin and norepinephrine levels in certain brain regions help the body to inhibit pain. When levels of serotonin and norepinephrine are low in certain brain regions, the nervous system becomes more sensitive to pain. Similarly, when serotonin and/or norepinephrine are low in other brain regions, this causes depression or anxiety. Because serotonin and norepinephrine are involved in both pain and in depression/anxiety, the same drug can be used to treat both conditions. Thus, although these drugs are often labelled as antidepressants, these drugs are directly improving pain and mood separately; not by indirectly improving pain by making depression better.

What are the names of some Antidepressants that are used to treat chronic pain?

SNRIs

• Duloxetine (Cymbalta, Irenka). This is the antidepressant that has the best evidence for treating many types of chronic pain (e.g., neuropathic pain, fibromyalgia, osteoarthritis, low back pain)
• Milnacipran (Savella). This drug is approved for use in fibromyalgia.
• Venlafaxine (Effexor, Effexor XR)
• Atomoxetine (Strattera)
• Desvenlafaxine (Pristiq, Khedezla)
• Levomilnacipran (Fetzima)

SSRIs

• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluvoxamine (Luvox)
• Volazodone (Viibrid)
• Vortioxetine (Brintellix)

Tricyclic antidepressants (TCAs)

• Amitriptyline (Elavil, Vanatrip)
• Nortriptyline (Pamelor)
• Desipramine (Norpramin)
• Imipramine (Tofranil)

Risks

Some of the more common side effects of antidepressants include:

• Nausea, constipation, diarrhea, stomach pain, upset stomach, throwing up, or feeling less hungry. These side effects are often worse when the person first starts taking the drug and gets better over a few days to weeks. These side effects are often improved by taking the drugs with food.
• Headache
• Dry mouth
• Trouble sleeping
• Feeling dizzy, sleepy, tired, or weak
• Sweating a lot
• Weight change (both gain or loss)
• Problems with sex

Some less common but more serious side effects of antidepressants include:

• Increased risk of suicide. Drugs like these may increase the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take antidepressants need to be watched closely – especially when they first start taking these drugs. Call the doctor right away if there are signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
• Allergic reactions. Several different types of serious allergic reactions can occur in response to these drugs.
• Serotonin syndrome. This is a rare but very serious syndrome associated with taking drugs that increase serotonin. Symptoms include agitation, confusion, changes in balance, flushing, palpitations, shivering or shaking, fever, headache and even seizures. Call the doctor right the way if you experience these symptoms.

What are anxiolytic drugs?

Anxiolytics include several types of medicines used to treat anxiety. The only anxiolytics that are used to treat chronic pain are some antidepressants described in the antidepressant section. These are mainly drugs that raise the levels of norepinephrine and serotonin in the brain.

Other anxiolytics however are commonly used in individuals who with chronic pancreatitis and anxiety. These are drugs that come from the benzodiazepine class. Such drugs include: alprazolam (Xanax, Niravam), clonazepam (Klonopin), diazepam (Valium), oxazepam (Serax), flurazepam (Dalmane), and lorazepam (Ativan).

The reason that we make particular mention of the benzodiazepine class of anxiolytic agents is that when these benzodiazepines are taken at the same time as opioid/narcotic pain pills, or alcohol, or both - they are particularly dangerous due to their effect on slowing down breathing. Each year, many of the people in the U.S. who die from overdose were taking opioids and benzodiazepines together- and many of these individuals are individuals with chronic pain.

What are antioxidants?

Antioxidants are substances that help protect the body's cells from damage caused by harmful substances called free radicals. These free radicals are built up in the pancreas in patients with chronic pancreatitis and can affect how the pancreas works. Antioxidants are found in many foods and sold as pills or capsules. In individuals with chronic pancreatitis, antioxidants may help reduce abdominal pain.

What are the names of some antioxidants?

Antioxidants are not prescribed medications and are not regulated. You can find a mix of antioxidants with vitamins in any drug store. You don't need a prescription to buy them. These doses have been studied in people with chronic pancreatitis and may help with pain:

• Methionine 2 grams.
• Beta-carotene (a precursor of vitamin A) 9000 IU.
• Vitamin C (ascorbic acid) 0.54 grams.
• Vitamin E (alpha-tocopherol) 270 IU.
• Selenium 600 mg.

Risks

Most antioxidants from food sources are considered safe. However, they can cause constipation, diarrhea, heartburn, nausea, abnormal taste (dysgeusia) and headaches.

Patients should consult with a healthcare provider before starting antioxidant supplements, especially if they have chronic illnesses or are taking multiple medications.

What are cannabinoids?

Cannabinoids are a class of active drug found in Cannabis sativa, also known as cannabis or marijuana. While there are over 100 active cannabinoids found in cannabis, the two most common and best-studied cannabinoids are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC and CBD have significantly different effects.

THC is responsible for the cannabis "high" and consequently, the abuse and addiction potential of cannabis. Therapeutically, THC can be used to stimulate appetite in chemotherapy-induced nausea and vomiting, help manage chronic pain, and help reduce muscle spasticity in multiple sclerosis. THC has not shown to be beneficial in reducing pain in patients with chronic pancreatitis.

CBD is non-intoxicating and has very little abuse potential. CBD can be used to decrease seizures in rare childhood epileptic conditions, such as Dravet syndrome. While there is much excitement about CBD's potential as a pain reliever, there are no published clinical trials showing that CBD alone is analgesic.

Are cannabinoids legal?

Cannabis is classified as a Schedule I substance under the Controlled Substances Act, which designates it as a drug with a high potential for abuse and no accepted medical uses. As such, cannabinoid products that come from the cannabis plant and contain more than 0.3% THC remain illegal under federal law. However, many States have medical and adult-use cannabis legislation that allows consumption of cannabis under State law. In those States, it is possible to legally obtain cannabis products, but they are still considered illegal at the federal level.

Hemp is a type of cannabis that contains less than 0.3% THC. In 2018, CBD that is derived from hemp became more widely available after hemp was removed from the Controlled Substances Act. However, how these products are going to be regulated is still an open question.

There are some FDA-approved cannabinoid medications. All FDA-approved medications with THC are synthesized in the lab rather than derived from the cannabis plant.

What are the names of some cannabinoid medications?

FDA-approved cannabinoids:

• Syndros (synthetic THC)
• Dronabinol (synthetic THC)
• Cesamet (nabilone, a THC analog)
• Epidiolex (plant-derived CBD)

Cannabis products that are not FDA-approved

• Hemp-derived CBD: CBD products derived from hemp are widely available online and in brick and mortar retailers. However, the quality of products and accuracy of labeling varies greatly from product to product. If buying these products, use caution and do your homework on the company selling the product. Make sure you look for products that have independent third-party testing for contaminants (such as heavy metals and pesticides) and potency.
• Medical Cannabis: There are many cannabinoid products that are available in States with laws that allow cannabis for medical or recreational purposes. These products do not undergo the same kinds of stringent testing required for pharmaceutical products. If you live in a State with legal medical cannabis, you may be able to obtain a medical cannabis license that would allow you to purchase cannabis products from medical cannabis dispensaries. If you choose to go this route, there are three important things to keep in mind:

Administration route: The effects of cannabis differ by how you use it.

• Smoking and vaporizing will result in fast-acting effects which can typically be felt in 5–15 minutes and last for 2–4 hours. However, smoking and vaporizing hurts the lungs, and should be avoided if possible.
• Edibles take anywhere from 30 minutes to 3 hours to take full effect, and last for 6–8 hours. When first taking an edible product, be sure to wait at least the full 3 hours before taking more so you do not overdose.
• Tinctures are infused cannabis oils or alcohol-based products that are held under the tongue for 1–2 minutes. Tinctures cause faster-acting effects than edibles (15–30 minutes) if used properly, and typically last 4–6 hours.
• Topicals (e.g. creams) are widely variable in composition, so it is uncertain how long it takes for them to take effect. It is also unclear how well topical cannabinoid products penetrate the skin, so it likely makes sense to use them directly on joints that are affected by pain or inflammation rather than using them to obtain a whole-body effect.

Dosing: "Start low, go slow"

People have different responses to cannabis based on their own unique make-up and past experience with cannabis. Lower doses may be medically effective, as well as helping avoid adverse side effects and building tolerance.

CBD to THC ratio

Since CBD has fewer side effects than THC and is non-intoxicating, you may want to start with CBD alone or a CBD-dominant product. If you choose to take THC, make sure you take it with CBD, as CBD may enhance THC's analgesic effects and reduce some THC-related negative effects.

Medical risks

People with a family or personal history of psychiatric illness, psychosis, or underlying heart conditions should be especially cautious when using cannabinoids. People should not drive or operate heavy machinery under the influence of THC. Because many CBD products are poorly regulated, people choosing to use hemp-derived CBD products should be very cautious about which products to buy, as some products have been shown to be either inaccurately labeled and/or contain contaminants such as pesticides, heavy metals, or mold. Some common side effects of THC include the following:

• Confusion
• Intoxication
• Dizziness
• Nausea
• Sleepiness

Some common side effects of CBD include the following:

• Malaise
• Diarrhea
• Sleepiness
• Poor quality sleep
• Fatigue
• Decreased appetite

In general, you should consult your healthcare provider if you want to use cannabinoids. This will allow you to develop goals for treatment, ways of tracking your progress, and making sure you and your healthcare provider are on the same page about how you are using these compounds.

Other risks

Taking cannabinoids may put your job at risk, as many employers perform urine drug screens for THC – even in States with legal adult use or medical cannabis laws.