Analgesic Medical Model

Seung J. Lee MD MBAUniversity of Maryland

School of Medicine Department of Anesthesiology

Division of Pain Medicine

Disclaimer

Dr. Seung J. Lee, MD, MBA does not have any financial conflict to disclose for this presentation

This presentation is intended to provide educational information related to Analgesic Medical Models including WHO analgesic ladder and multi-modal analgesia

The speaker is not promoting any particular services or products

Objectives

Following the presentation, the participants should be able to:

1. Describe WHO analgesic ladder and its limitations2. Set different goals for acute pain vs chronic pain

treatments3. Recognize need to use a multi-modal analgesia plan,

rather than unimodal opioid therapy

The World Health Organization

Analgesic Ladder for cancer pain

■ Initially presented in 1986

■ Framework for the physicians

■ Increased Awareness■ Inexpensive■ Effectiveness: 80 – 90 %

(perhaps 70 - 80%)

Vargas-Schaffer, G. (2010)

WHO Analgesic Ladder 1986

WHO Ladder - Limitation

■ The pharmacological approach

■ No interventional options

■ Only designed for cancer pain

■ Mainly focused on opioid medications

Step 1:

Step 2:

Step 3:

PALLIATIVE CARE –give more opioids ??

Proposed Modification of the WHO Analgesic

Ladder (2010)

Vargas-Schaffer, G. (2010)

Modifications are necessary to ensure its continued use for knowledge transfer in pain management

Step up, step down: bidirectional approach

Treat different type of pain: Acute pain, chronic non-cancer pain, and neuropathic pain

Vargas-Schaffer, G. (2010)

Multimodal Model (2019)

■ Dynamic model

■ Patient tailored therapies

■ Pharmacological agents

■ Non-pharmacological methods

■ Transition from opioid mono-therapy

Cuomo, A., Bimonte, S., Forte, C., Botti, G., & Cascella, M. (2019)

Wren, Anava et al (2019) Tompkins, D., Hobelmann, J., & Compton, P. (2017).

Impact of A Multidisciplinary Pain Management Program on Patient Care Utilization and Cost of Care

■ Patients enrolled in MPP were less likely to use expensive diagnostic imaging and experienced fewer hospitalizations, resulting in total cost of care savings

Maeng, D., Baylor, K., Bulger, J., & Han, J. (2018).

Pain

■ "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage“ (IASP definition)

■ can be an adaptive sensation, an early warning to protect the body from tissue injury

■ by the introduction of hypersensitivity to normally innocuous stimuli, pain may also aid in repair after tissue damage

■ Perception of pain is a product of brain’s abstraction and elaboration of sensory input

Pain

• Acute pain– suddenly in response to a

specific injury– lasts a relatively short time – no definite time frame, but

most of cases, the pain does not last six months

– disappears when underlying cause of the pain is treated

– Example: Post-operative pain

• Chronic pain– defined as pain that

persists even though an injury has healed

– may not have specific causes

– may be more difficult to treat

– usually 3-6 months

Wren, Anava & Ross, Alexandra & D’Souza, Genevieve & Almgren, Christina & Feinstein, Amanda & Marshall, Amanda & Golianu, Brenda. (2019)

Wren, Anava et al (2019) Tompkins, D., Hobelmann, J., & Compton, P. (2017).

Targets for Multi-modal Therapy: Post-operative Pain

LOCAL ANESTHETICS

ACETAMINOPHEN & NSAIDS KETAMINE

ANTICONVULSANTS ALPHA-2-AGONISTS OPIOIDS

Multi-modal Therapy: Post-operative Pain

Devin, C. J., & McGirt, M. J. (2015).

Targets for Medication Therapy: Ambulatory Setting

ACETAMINOPHEN & NSAIDS

ANTIDEPRESSANTS ANTICONVULSANTS MUSCLE RELAXANTS TOPICAL OPIOIDS

OTHERS

Acetaminophen and NSAIDs■ NSAIDs are more effective in musculoskeletal pain compared to neuropathic pain

■ NSAIDs may act at the site of injury and decrease the pain associated with an inflammatory reaction

■ Acetaminophen can relieve pain in mild arthritis, but has no effect on the underlying inflammation, redness, and swelling of the joint.

■ The exact mechanism of action of acetaminophen is not known. It may reduce the production of prostaglandins in the brain

■ Acetaminophen and NSAIDs have different mechanisms of action and research indicates that the combination of acetaminophen with NSAIDs might be more effective than either drug alone

Example of NSAIDs

Ibuprofen

Naproxen

Meloxicam

Diclofenac

Ketorolac

Indomethacin

Celecoxib

Anti-depressants

■ The analgesic effects of antidepressants are thought to be independent of their antidepressant effects

■ Enhance the descending-pain inhibitory system by preventing cellular re-uptake of serotonin and norepinephrine

■ May affect the central component and the emotional aspects of pain

■ Neuropathic pain

Anti-depressants

Tricyclic antidepressants■ Amitriptyline (Elavil)

■ Nortriptyline (Pamelor)

Serotonin/norepinephrine reuptake inhibitors

■ Venlafaxine (Effexor XR)

■ Duloxetine (Cymbalta)

■ Milnacipran (Savella)

■ Desvenlafaxine (Pristiq)

Anticonvulsants

■ Inactivate the sodium channels in afferent fibers and thereby inhibit the action potential

■ Some works in calcium channels and it blocks the release of glutamate

■ Neuropathic pain

Anticonvulsants

Gabapentin (Gralise,

Neurontin, Horizant)

Pregabalin (Lyrica)

Skeletal Muscle Relaxants

■ Most of them work on the central nervous system

■ Many do not have exact mechanism and different classes of medications

■ Few work at muscle fibers – Dantrolene– Botox

Muscle Relaxants

■ Carisoprodol (Soma)■ Diazepam (Valium)

■ Cyclobenzaprine (Flexeril)■ Metaxalone (Skelaxin)■ Methocarbamol (Robaxin)■ Baclofen (Lioresal)■ Tizanidine (Zanaflex)

Topical Medications

■ Lidoderm patch/gel■ Diclofenac patch/gel■ Capsaicin

– 0.025% to 0.075% and 0.1% creams– Capscicin 8% patch– topical cream that depletes substance P from the primary

afferent nociceptor

Opioids

■ Ascending pathway– primary afferents to pain transmission neurons– inhibit dorsal horn pain transmission neurons– inhibit excitatory transmitters release from these primary afferents

■ Action in both supraspinal and spinal sites ■ Descending pathways

– rostral ventral medulla – locus ceruleus– midbrain periaqueductal gray

■ Administration of exogenous opioids promotes release of endogenous opioids

https://psychopharmacologyinstitute.com/clinical-psychiatry/substance-use-disorders/buprenorphine-opioid-use-disorder-mechanism-action/

https://psychopharmacologyinstitute.com/clinical-psychiatry/substance-use-disorders/buprenorphine-opioid-use-disorder-mechanism-action/

Other Medications■ Steroids

■ inhibit the arachidonic acid cascade and thereby inhibit synthesis of prostaglandins and leukotrienes

■ these drugs are powerful analgesics, particularly when there is tissue injury such as occurs with excessive peripheral edema, burns, arthritis, and bone metastasis

■ Calcitonin■ Relieve osteoporotic back pain and neuropathic pain

■ Omega 3■ Turmeric ■ Magnesium Oxide■ Cannabinoids

CANNABINOIDS:a class of chemical compounds that act

on cannabinoid receptors; the active

constituents of cannabis

Endogenous Cannabinoid

Receptors

■ A cannabinoid receptor in the CNS was identified in 1988

■ Receptors occur in many brain areas.

■ Cannabinoid receptors are metabotropic– work via G proteins to inhibit

cAMP formation– inhibit voltage-sensitive Ca2+

channels– open K+ channels

https://www.comfortleaf.com/the-endocannabinoid-system/

>100 cannabinoids in the plant. Most are non-psychoactive

Each has its own pharmacological actions and therapeutic potential

“Entourage” effects

The College of Family Physicians of Canada guideline

Advised doctors to not authorize medical cannabinoid

■ Are under the age of 25 (Level II)

■ Have a personal history or strong family history of psychosis (Level II)

■ Have a current or past cannabis use disorder or another active substance use disorder (Level III)

■ Have cardiovascular or respiratory disease (Level III)

■ Are pregnant, planning to become pregnant or are breastfeeding (Level II)

https://cannabisresearch.mcmaster.ca/news/2017/11/01/who-shouldn-t-use-medical-cannabis

The Hypothesis That Use Of Cannabis Is Causally Related To Risk Of Schizophrenia

https://www.nature.com/articles/mp2016252

Cannabinoids in chronic painSystematic review: Whiting et al JAMA June 2015

■ There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs

Pain Medication Targets

Transduction

TransmissionModulation

Perception/Brain

Dorsal rootganglia

Dorsal horn

Sensorycortex

Peripheral nociceptors

NSAIDs, steroid and anti-histamine. Peripheral nerve blockade with local anesthesia. Topical Medications

Opioid and anticonvulsants. Epidural and spinal nerve blockade with local anesthesia

Opioid, alpha 2 agonist and SNRI/TCA

CNS Response Opioid, alpha 2 agonist, ketamine, acetaminophen, cannabis and SNRI/TCA

Muscle Relaxants

REFERENCES

■ Vargas-Schaffer, G. (2010). Is the WHO analgesic ladder still valid?: Twenty-four years of experience. Canadian Family Physician, 56(6), 514.

■ Cuomo, A., Bimonte, S., Forte, C., Botti, G., & Cascella, M. (2019). Multimodal approaches and tailored therapies for pain management: the trolley analgesic model. Journal Of Pain Research, Volume 12, 711-714.

■ Tompkins, D., Hobelmann, J., & Compton, P. (2017). Providing chronic pain management in the “Fifth Vital Sign” Era: Historical and treatment perspectives on a modern-day medical dilemma. Drug And Alcohol Dependence, 173, S11-S21.

■ Pain: Hope Through Research | National Institute of Neurological Disorders and Stroke. (2020). Ninds.nih.gov. Retrieved 22 February 2020, from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Pain-Hope-Through-Research

■ Chou, R., Gordon, D., de Leon-Casasola, O., Rosenberg, J., Bickler, S., & Brennan, T. et al. (2016). Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. The Journal Of Pain, 17(2), 131-157.

REFERENCES

■ Nielsen, S., Sabioni, P., Trigo, J., Ware, M., Betz-Stablein, B., & Murnion, B. et al. (2017). Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis. Neuropsychopharmacology, 42(9), 1752-1765.

■ Maeng, D., Baylor, K., Bulger, J., & Han, J. (2018). Impact of a multidisciplinary pain management program on patient care utilization and cost of care. Journal Of Pain Research, Volume 11, 2375-2383. doi:10.2147/jpr.s177231

■ Wren, Anava & Ross, Alexandra & D’Souza, Genevieve & Almgren, Christina & Feinstein, Amanda & Marshall, Amanda & Golianu, Brenda. (2019). Multidisciplinary Pain Management for Pediatric Patients with Acute and Chronic Pain: A Foundational Treatment Approach When Prescribing Opioids. Children. 6. 33. 10.3390/children6020033.

■ Multimodal Analgesia and Alternatives to Opioids for Postoperative Analgesia - Anesthesia Patient Safety Foundation. (2018). Anesthesia Patient Safety Foundation. Retrieved 22 February 2020, from https://www.apsf.org/article/multimodal-analgesia-and-alternatives-to-opioids-for-postoperative-analgesia/

■ Schuster, Michael, Oliver Bayer, Florian Heid, and Rita Laufenberg-Feldmann. 2018. “Opioid Rotation in Cancer Pain Treatment: A Systematic Review.” Deutsches Aerzteblatt International 115 (9): 135–42. doi:10.3238/arztebl.2018.0135.