Opioid analgesics

In the midst of an opioid overdose epidemic, U.S. healthcare providers must:

1. educate patients/families and the public at large regarding the risks and benefits of opioid substances and medications,
2. ensure optimum pain relief to promote healing and quality of life,
3. guard against drug diversion, unintended opioid dependance, and opioid related morbidity and mortality. (Click graphic to expand and again to minimize)

Opioid – A natural, synthetic, or semi-synthetic chemicals that interact with opioid receptors on nerve cells in the spinal cord and brain, and reduce the intensity of pain signals and feelings of pain (CDC 2021).

This class of drugs includes the illegal drug heroin, synthetic opioids such as fentanyl, and commonly prescribed pain medications,e.g., oxycodone, hydrocodone, codeine, morphine, and many others. (Click graphic to expand and again to minimize)

How opioid analgesics work: a very basic explanation

Opioid receptors modulate nociception and many other physiologic functions, by inhibiting the release of neurotransmitters. Opioid agonists (morphine, heroin, fentanyl, etc.) administered for pain activate Mu opioid receptors at the presynaptic afferent terminals and postsynaptic terminals located in the spinal dorsal horn (SDH) nerves. Activation of SDH Mu receptors by opioids can reduce the neurotransmission of nociceptive signal to the ascending spinothalamic tract (Corder G. 2018). (click graphic to expand and again to minimize)

If the quantity and frequency of peripheral action potentials exceed the Mu inhibition at the SDH neurotransmission may continue up the spinothalamic tract, to the thalamus and somatosensory cortex, where additional Mu receptors await to blunt the neurotransmsission. However, if the somatosensory cortex perceives pain, it can send signals down descending pain pathway to the SDH. Mu receptors activated by the descending pathway cause the release of endogenous opioid substances (endorphines and enkephalins) in the SDH. Endogenous opioids are the natural ligands of opioid receptors that play a role in neurotransmission, pain modulation, and other homeostatic functions.

2022 CDC Recommendations for treatment of pain with opioids (Full 2022 CDC Opioid Guidelines Click here )

All patients with pain should be informed of the treatment options and receive the appropriate treatment that provides the greatest benefits relative to risks.

1. Nonopioid therapies are are preferred for subacute and chronic pain, and may be as effective as opioids for many common acute pain conditions, including low back pain, neck pain, pain related to other musculoskeletal injuries (e.g., sprains, strains, tendonitis, and bursitis), pain related to minor surgeries typically associated with minimal tissue injury and mild postoperative pain (e.g., simple dental extraction), dental pain, kidney stone pain, and headaches including episodic migraine.
   1. Non-opioid pharmacologic treatment, e.g.,topical, oral or systemic NSAIDs, acetaminophen.
      1. Neuropathic pain: tricyclic, tetracyclic, and SNRI antidepressants; selected anticonvulsants (e.g., pregabalin, gabapentin enacarbil, oxcarbazepine); and capsaicin and lidocaine patches
      2. Peripheral neuropathies, e.g. diabetic (Duloxetine and pregabalin) and postherpetic (pregabalin and gabapentin)
      3. Fibromyalgia treatments include: tricyclic and SNRI antidepressants (e.g., duloxetine, milnacipran), NSAIDs (e.g., topical diclofenac), and specific anticonvulsants (i.e., pregabalin and gabapentin) are used to improve pain, function, and quality of life
      4. Nonpharmacologic treatment, e.g., ice, heat, elevation, rest, immobilization,
         1. osteoarthritis of the knee or hip: exercise, weight loss, behavioral therapies, manual therapies for hip osteoarthritis
         2. low back pain: psychological therapy, spinal manipulation, low-level laser therapy, massage, mindfulness-based stress reduction, yoga, acupuncture, and multidisciplinary rehabilitation
         3. neck pain: mind-body practices (e.g., yoga, tai chi, and qigong), massage, and acupuncture
         4. tension headache
2. Opioid therapy has an important role for acute pain related to severe traumatic injuries (including crush injuries and burns), invasive surgeries typically associated with moderate to severe postoperative pain, and other severe acute pain when NSAIDs and other therapies are contraindicated or likely to be ineffective.

   Opioids prescribed for severe acute pain should be

   1. immediate release opioids
   2. lowest effective dose
   3. for no longer than the expected duration of pain severity will require opioids
      
      
3. Opioids should be prescribed for use "As needed" rather than on a scheduled basis and encourage tapering after more than a few days.
4. Long-term opioid use:  these patients that require additional medication for new acute pain should try non-opioids when possible.  If additional opioids are required "they should be continued only for the duration of pain severe enough to require additional opioids, returning to the patient’s baseline opioid dosage as soon as possible, including a taper to baseline dosage if additional opioids were used around the clock for more than a few days".

References

Corder, G., Castro, D. C., Bruchas, M. R., & Scherrer, G. (2018). Endogenous and Exogenous Opioids in Pain. Annual review of neuroscience, 41, 453–473. https://doi.org/10.1146/annurev-neuro-080317-061522

Centers for Disease Control and Prevention. (2021). Commonly used terms. Centers for Disease Control and Prevention. https://www.cdc.gov/opioids/basics/terms.html CDC (2022). National Center for Health Statistics. Drug Overdose Mortality by State. https://www.cdc.gov/nchs/pressroom/sosmap/drug_poisoning_mortality/drug_poisoning.htm

Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. (2022). CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1–95. DOI: http://dx.doi.org/10.15585/mmwr.rr7103a1

Dhaliwal A, Gupta M. Physiology, Opioid Receptor. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546642/

Herman TF, Cascella M, Muzio MR. Mu Receptors. [Updated 2023 Jul 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551554/

Parthipan, A., Banerjee, I., Humphreys, K., Asch, S. M., Curtin, C., Carroll, I., & Hernandez-Boussard, T. (2019). Predicting inadequate postoperative pain management in depressed patients: A machine learning approach. PloS one, 14(2), e0210575. https://doi.org/10.1371/journal.pone.0210575

Williams J. (2008). Basic Opioid Pharmacology. Reviews in pain, 1(2), 2–5. https://doi.org/10.1177/204946370800100202