Medications for Chronic Pain

Introduction: the 5 S's

  • Medications may be helpful in achieving this goal for some people, when combined with healthy habits such as improving sleep and reducing stress.
    • There is no magic pill to cure pain
  • Every individual’s response to medication is unique.

 

Balance benefits and risk

  • It is important to select the safest medication for you
  • This means balancing the benefit from the medication with the associated risks.
  • Significant pain relief from medications is defined as a 30% reduction in pain intensity.

 

  • Strike a balance between risks and benefits

    • It is important to balance the medications’ benefit for pain reduction with that its side effects and risks
    • Harm exists in both under-treating your pain as well heavily relying on medications and being over prescribed medications.
  • Side effects

    • All medications come with a potential for side effects; it is important to know what to expect when starting a new medication.
  • Safe use

    • Take your medications as prescribed.
    • Be aware of common interactions with other medications and substances.
    • Do not borrow medications
    • Do not share your medications
  • Self-medications

    • Know what, when, why, and how you take your medications.
    • Maintain a current list of your medications (including herbals, vitamins, and over the counter medications) to share with your health care team.
    • Your community and clinic pharmacists can help you.
  • Safe storage and disposal of medications

    • Store medications securely (e.g., locked or out of reach from kids and pets).
    • Avoid areas of heat and moisture such as the bathroom or over the stove.
    • Leave medications in their original labelled containers.
    • Please bring back unused medications to your community pharmacist for appropriate disposal

Key concepts:

  • Medications are only one aspect and tool for persistent pain management.
  • There is no magic pill to cure pain.
  • Pain medications can reduce your pain intensity by 30% at best.
  • Goal of medication therapy is optimal health and improved overall function.
  • Consider the 5 S’s of medications.

Types of Medication and Chronic Pain

  • When treating chronic pain, many analgesic medications may be used.
  • The choice of medication depends on the cause of the pain and the type of pain.

There are two main kinds of chronic pain and they require different treatments. 

  • Nociceptive pain

     is caused by tissue damage or injury which affect pain sensors known as nociceptors. It may include pain due to inflammation such as arthritis, mechanical/compressive types of pain such as pain caused by expanding tumors or pain from inflammatory bowel disease.

  • Neuropathic pain

    is caused by a lesion or dysfunction in the nerve or the central nervous system. It may be peripheral such as diabetic neuropathy or post-herpetic neuralgia; or it may be central such as post-stroke pain, pain due to spinal cord injury or multiple sclerosis.

  • Nociplastic pain

    Pain that arises from changes in how the sensory systems responds to a harmful/ potentially harmful stimuli, despite no clear evidence of actual or threatened tissue damage or evidence for disease or lesions causing the pain.

     

    This term helps describe pain that underlies many different chronic pain conditions, including fibromyalgia, complex regional pain syndrome, other types of musculoskeletal pain such as chronic low back pain, as well as visceral pain disorders such as irritable bowel syndrome and bladder pain syndrome.

Pain Ladder

After a clinical assessment, your doctor may suggest trying a specific medication. Their recommendations are based on 1) the type of pain you have, 2) how severe your pain is, 3) and other factors (like your medical and family history).  It is important to try out a medication for a sufficient amount of time (~several weeks) before one can see its full effect.  Sometimes, it also takes a couple of tries to figure out the best medication(s) and dosage for each patient. 

Key concepts:

  • Finding a medication that helps manage your pain is a process
  • Medications that work for one patient may not work for another patient
  • Medications are just one way to support pain management, they often work best when combined with other therapies

Choice of pain relieving medication

There are many different agents used to relieve pain. They include simple analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as antidepressants, anticonvulsants, local anesthetics, opioids and cannabinoids.

  • Acetaminophen

    • A simple analgesic used to relieve mild to moderate nociceptive pain.
    • It is well-tolerated and relatively safe when taken appropriately.
    • Acetaminophen is present in many over-the-counter products such as Tylenol®, Robaxacet® and cough and cold products e.g. DayQuil®.
    • It is important to consider the amount of acetaminophen in these products so as not to exceed the Health Canada recommended daily maximum dose of 4000mg/day.
    • However, it is also important to check with your primary care provider what your maximum daily dose should be, as it may be lower in liver disease, advanced age, or with chronic acetaminophen use.  
  • Non-steroidal anti-inflammatory agents

    • This medication decreases inflammation, and changes the pain system in the brain and spinal cord.
    • They are used to relieve nociceptive pain such as osteoarthritis.
    • NSAIDs may cause stomach irritation, which in severe cases can lead to stomach bleeds and/or ulcers.
    • They can also increase blood pressure, alter blood clotting, and may contribute to kidney damage and increases the risks of heart attacks and strokes
    • NSAIDs can increase the risk of bleeding when combined with aspirin, anticoagulants, and some antidepressants.
    • However, it is important to note that the body does not develop tolerance to NSAIDs, and they do not lead to physical dependence.

    NSAIDs include ibuprofen (Motrin®, Advil®, Robax Platinum), naproxen (Aleve®) and celecoxib (Celebrex®). Celecoxib is a specific type of NSAID known as a COX-2 inhibitor. It carries a lower risk of stomach irritation, but may still affect your kidney and cardiovascular system.

  • Antidepressants

    • These medications can increase serotonin and norepinephrine levels in the nervous system and decrease overall pain sensation and in doing so can improve mood.
    • Some commonly used antidepressants include duloxetine (Cymbalta®), venlafaxine (Effexor®) and the tricyclic antidepressants (amitriptyline, nortriptyline).
    • There is evidence they may be useful in neuropathic pain, fibromyalgia and some arthritis (duloxetine). 

    Below are dosing and side effect considerations:

     Medicine
     Usual dose  Common side effects
     Duloxetine  30-90 mg  Nausea, headache, sleep   problems, sexual problems
     Venlafaxine  ~225mg
     Amitriptyline  10-75 mg at bedtime  Weight gain, Dry mouth
     Drowsiness, Constipation
     Heart rhythm problems
     Nortriptyline  25-50 mg at bedtime
  • Anticonvulsants

    • The proposed mechanism is by reducing the release of excitatory brain chemicals in the spinal cord and brain, thereby reducing the pain sensation.
    • The anticonvulsants that have been shown to be effective in relieving neuropathic pain and fibromyalgia are gabapentin (Neurontin®) and pregabalin (Lyrica®).
    • Gabapentin and pregabalin may cause drowsiness, dizziness, confusion, dry mouth, weight gain or headaches.
    • These side effects are usually temporary and may be managed in different ways, such titrating up these medications gradually, or taking them at bedtime.
    • Other anticonvulsants that have specific roles include carbamazepine (Tegretol®) for trigeminal neuralgia; and topiramate (Topamax®) for migraine prevention.

     

     Medicine 
     Usual dose  Common side effects

     Gabapentin

     

     1200-2400mg/day

    Drowsiness, Dizziness, Change in balance, Change in thinking clearly, Dry mouth, Weight gain,
    Headache
    Less common: Swelling in the legs, blurry eyesight, euphoria

    Pregabalin

    300-600 mg/day

Key concepts:

  • Everyone responds to medication differently
  • Your doctors may have you try medications depending on the type of pain that you have and your medical history
  • Your local pharmacist knows a lot about medications- you can go to them anytime to discuss side effects, address concerns, or to learn more.

Opioids for Acute Pain

  • Opioids block pain signals in your brain and spinal cord.
  • They are very effective to manage moderate to severe acute pain such as pain following surgery, injury, or due to disease (cancer tumors).
       


Opioids and Chronic Pain

  • The 2017 opioid guidelines suggest that non-opioid medications be used first.
  • There are significant health risks associated with long term opioids and these risks increase with dose.
  • Opioids should only be used if they allow you to improve your function and achieve practical goals.
  • It is important to note that there is no strong evidence or good quality studies demonstrating that opioids are effective in chronic pain management.
  • Studies have shown that patients receiving long term opioid therapy experience worse overall body pain,  function, and mood than patients with similar pain conditions who are not taking opioids.

Opioids & your safety:

  • Remember, if you interrupt your opioids for 3 days or more, DO NOT resume taking your original opioid doses without first consulting your doctor because your body might have lost tolerance and doing so could put you at risk for an overdose.
    • If you take opioids, have a Naloxone kit for overdose prevention-you can get one for FREE from your community pharmacist 
  • The use of prescription opioids can have a number of side effects. 
  • Speak to your doctor if you have any of these side effects

    • Constipation, nausea and/or vomiting, dry mouth
    • Sleepiness, dizziness and confusion
    • Itching and sweating
    • Reduced urge to breathe (respiratory depression)
    • Medical complications that include:
      • Low levels of testosterone (lower sex drive, energy, strength and effects on fertility)
      • Increased fracture risk
      • Increased sensitivity to pain
      • Sleep apnea
      • Lower mood
      • Lower immunity
      • Addiction

These risks can be minimized by working together with your healthcare team and by being honest with your medication experiences. 

 

Cannabinoids

Cannabis is not one product or chemical, in fact it contains more than 500 chemicals. We know the most about THC and CBD.

  • Cannabis is available as dry plant (buds), oils, tinctures, sprays, creams and edibles.
  • Highly potent and concentrated recreational cannabis is available as shatter, wax
  • Cannabinoids are also available as pharmaceutical products these include nabilone (Cesamet) and Sativex
 

The effect of cannabis 

  • The effect of cannabis differs from person-to-person and depends on:
    • your biological make-up and past experiences with cannabis
    • the strain of plant in the product and the amount of THC and CBD
    • how you take it and how much you use
    • other medications or substances you may use
  • Potential Benefits

    • There is currently not a lot of good scientific evidence supporting the use of cannabis in chronic pain. 
    • Medical cannabis has been shown in small studies
      to have some benefit in certain people with:
      • neuropathic or “nerve” pain
      • palliative and end-of-life pain
      • spasticity (multiple sclerosis or spinal cord injury)
  • Potential Harms

     

    Cannabis related side effects are primarily due to the THC content.  Harms occur more frequently in those who use cannabis daily, smoke cannabis and/or use high THC strains.  Cannabis can:

    • Decrease thought-processing and reaction time
    • Impair perception, memory, concentration, and decision-making
    • Can cause cycles of severe nausea and vomiting
      (Cannabis Hyperemesis Syndrome)
    • Lead to bronchitis, lung infections, and chronic cough
    • Worsen symptoms of anxiety, depression, or can cause psychosis
    • Worsen mania symptoms in bipolar disease and PTSD symptoms
    • Lead to dependence or addiction
  • Cannabis is NOT recommended if ...

    If you are:

    • allergic to any cannabinoids
    • pregnant or breastfeeding
    • under the age of 25

    If you have:

    • history of heart or lung disease
    • personal or family history of serious mental illness
    • current or past cannabis use disorder or other substance use disorders

Ways to use safely

  • Choose products with lower THC
  • Avoid synthetic cannabis products (ie K2, spice)
  • Only purchase cannabis from a Health Canada licensed producers
  • Ingest cannabinoid oils instead of vaporizing or smoking cannabis
  • Do not use cannabis in combination with alcohol or other medications that cause sedation
  • Store your cannabis in a locked container
  • Do not give or sell your cannabis to others
  • Do not drive for at least four hours after inhalation, six hours after oral ingestion, and eight hours after experiencing a high.

Key concepts:

  • Studies have shown small, short term benefits for very select types of pain conditions such as neuropathic pain.
  • Cannabis may minimally improve sleep.
  • Studies have not shown much benefit for other types of pain.
  • Regular use causes harmful health effects.

Other Medications

  • Muscle relaxants

    Muscle relaxants, such as baclofen or cyclobenzaprine are sometimes used to help relieve muscle spasms that may be contributing to pain. Their most common side effect is drowsiness and dizziness.

  • Topically applied agents

    • Topically applied agents can be used to treat localized painbut that are often not the most effective agent for more widespread pain. Some agents include:

      • Lidocaine gel and capsaicin cream-may be useful in treating localized neuropathic pain such as post-herpetic neuralgia
      • Capsaicin cream is derived from the chilli pepper.   Capsaicin helps relieve pain by depleting the pain inducing neurotransmitter called substance P in the nerve endings.  This prevents your brain from receiving pain impulses. For the first couple of weeks of use, it may cause local burning or stinging as substance P is released, but this is temporary as substance P is ultimately depleted.  It must be applied several times a day to keep substance P from building up again. 
      • Anti-inflammatory creams and lotions, available over the counter (ex Voltaren Emugel) and by prescription (Pennsaid)”
      • Your primary care provider may also prescribe a compounded cream that has a variety of ingredients to help neuropathic pain.
  • Herbal remedies

    • Although herbal products seem ‘natural,’ it does not mean that they are safe or effective. Herbal medications have not been well studied.
    • Herbals medications can interact with your other prescription medications.
    • It is important to let your pharmacist know that you are taking them.

Conclusion

  • Medications are only one piece of the puzzle in managing persistent pain.
  • The main goal of medication is to achieve optimal health and improve overall function.
  • There are multiple types of medications to manage persistent pain.
  • Opioids have a role in acute pain, but there is limited evidence in persistent pain.
  • Cannabinoid risks may outweigh its benefits.
  • Herbals have little evidence and may interact with your other medications.

References

  1. WHO Pain Relief Ladder for cancer pain relief. Available at: www.who.int/cancer/palliative/painladder/en/ (accessed 21 November 2017).
  2. Chronic pain management. Lexicomp Online [database online]. Hudson, OH: Lexicomp, Inc. http://online.lexi.com. Updated September 15, 2016. Accessed November 13, 2017.Lexi-comp (http://online.lexi.com.myaccess.library.utoronto.ca/lco/action/doc/retrieve/docid/patch_f/5261)
  3. DRUGDEX® System [database online]. Greenwood Village, CO: Truven Health Analytics. http://www.micromedexsolutions.com/. Updated March 25, 2009. Accessed November 14, 2017.
  4. Guideline for the evidence-informed primary care management of low back pain. Hamilton (ON): McMaster University; 2009. Available: http://nationalpaincentre.mcmaster.ca/documents/LowBackPainGuideline.pdf. (Accessed November 21, 2017).
  5. Busse J. The 2017 Canadian guideline for opioids for chronic non-cancer pain. Hamilton (ON): McMaster University; 2017. Available: nationalpaincentre.mcmaster.ca (Accessed November 12, 2017).
  6. Cannabinoid Buccal Spray for Chronic Non-Cancer or Neuropathic Pain: A Review of Clinical Effectiveness, Safety, and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Sep 21. Summary of Evidence. Available from: https://www.ncbi.nlm.nih.gov/books/NBK395793
  7. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on the Health Effects of Marijuana: An Evidence Review and Research Agenda. The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research. Washington (DC): National Academies Press (US); 2017 Jan 12. COMMITTEE ON THE HEALTH EFFECTS OF MARIJUANA: AN EVIDENCE REVIEW AND RESEARCH AGENDA. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425770/
  8. Moulin DE, Boulanger A, Clark AJ, et al. Pharmacological management of chronic neuropathic pain: Revised consensus statement from the Canadian Pain Society. Pain Res Manag 2014; 19(6): 328-335.
  9. Watson, CP, Neuropathic pain, Compendium of Therapeutic Choices. Canadian Pharmacists Association, Updated May 2017. Accessed Nov 10, 2017.

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