A Pain Management Primer for Pharmacists

Jessica Geiger-Hayes, PharmD, BCPS, CPE

Andrea Wetshtein, PharmD, BCPS, CPE

Objectives

• Discuss the differences between somatic, visceral, and neuropathic pain

• Design a treatment plan for the different modalities of pain

What is Pain?

“An unpleasant sensory and emotional response associated with actual or potential tissue damage or described in terms of such damage.” (IASP)

International Association for the Study of Pain. IASP Pain Terminology. www.iasp-pain.org/terms-p.html

Whitten CE, Donovan M, Cristobal K. Treating Chronic Pain: New Knowledge, More Choices

What is Pain?

“Pain is whatever the person says it is”

-Margo McCaffery

Types

Acute vs Chronic

Nociceptive vs Neuropathic vs Mixed

American Pain Foundation: http://www.painfoundation.org/learn/publications/files/PainResourceGuide2009.pdf

Associated Syndromes

Hyperalgesia

• Increased pain sensitivity to a normally noxious stimulus

Allodynia

• Pain in response to a stimulus which is normally not noxious• i.e. blankets, clothing

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Nociception

Activation of peripheral nerve receptors by a noxious stimulus

Thermal

Chemical

Mechanical• Pressure• Stretch

Patient with Pain

PhysicalSymptoms

EmotionalPsychological

Problems

SocialConcerns

SpiritualExistential

Distress

Total Pain

How Pain Works4. Perception

3. Transmission

1. Transduction

Modulationhappens all along the way

Noxious Stimuli

2. Conduction

How Pain Works

Transduction• Conversion of mechanical or chemical stimuli into an electric charge

Conduction• Impulses from primary nociceptors to the spinal cord

Transmission• Transmitting nociceptive impulses from the dorsal horn to supra-spinal targets

Perception• Subjective awareness of pain

Modulation• Reduction of transmission

How Pain Works

Excitatory Neurotransmitters Substance P

Substance K

Glutamate

Aspartate

Calcitonin gene related peptide

Vasoactive intestinal peptide

Inhibitory Neurotransmitters Serotonin

Norepinephrine

Opioids

GABA

Somatostatin

Galanin

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Nociceptive Pain

Somatic PainSkin, soft tissue, bone• Easy to describe, localize

Visceral PainOrgans• Difficult to describe, localize

Described as…SharpAchingThrobbing

Neuropathic Pain

Nervous System Damage

Primary lesion

Dysfunction

Pain may be greater than

observable injury

Described as:Burning

Electrical

Shooting

Stabbing

Tingling

Wolf CJ. Ann Intern Med. 2004.

Assessment

Precipitating and palliating factors, previous tx

Quality

Region and radiation

Severity

Temporal profile

U (you)• How does the pain affect the patient

Patient Case

MC is a 56 y.o. male with metastatic NSCLC with new bone metastasis, uncontrolled DM2, and HTN

• Reports continuous 8/10 generalized pain and 10/10 pain in his L hip which he reports is negatively affecting his ability to take care of his family

• Described “sharp, aching, throbbing pain in his L hip”, feels as if his feet “are always on fire”

Current Pain Medications:Oxycodone ER 120 mg PO TID

Oxycodone 80 mg PO Q3H prn

Gabapentin 300 mg PO TID

Treatment Options

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Treatment options

Transduction – anti-inflammatories, local anesthetics

Conduction – opioids

Transmission –NMDA receptor antagonists, gabapentinoids, anti-epileptics, opioids, lidocaine/mexilitine

Perception – NO DRUGS!• THC may play a role here

• Cognitive behavioral therapy

Modulation – enhancing descending inhibitory pathway (opioids, TCAs, SNRIs, etc.)

Rational Polypharmacy

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Brain

Spinal Cord

PNS

Descending Inhibition(NE, 5HT)

Central Sensitization(Ca2+ channels, NMDA receptors)

Peripheral Sensitization (Na+ channels)

NSAIDsOpioidsTCALidocaine

TCAGabapentinOpioids

TCA SNRITramadolOpioids

Mechanism-Specific TreatmentMultiple targets…

Medications Affecting Transduction

Non-steroidal anti-inflammatories (NSAIDs)

Local anestheticstopical lidocaine

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Medications Affecting Conduction

• Opioids

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Full Mu Agonists Partial Mu Agonists

Agonist/Antagonist

Oxycodone Hydrocodone Buprenorphine Pentazocine

Codeine Morphine Butorphanol

Hydromorphone Fentanyl Nalbuphine

Meperidine Tramadol*

Tapentadol* Methadone**

Opioid ReceptorsOpioid Receptor

ClassAnalgesic Effects Adverse Effects

Mu1 Supraspinal analgesia Euphoria, confusion, dizziness, nausea, low addiction potential

Mu2 Spinal analgesia Respiratory depression, cardiovascular and GI effects, miosis, urinary retention

Delta Spinal analgesia Cardiovascular depression, decreased brain and myocardial oxygen demand

Kappa Spinal analgesia Dysphoria, psychomimetic effects, feedback inhibition of endorphin system

Global J. Pharmacol. 2009; 3(3):149-53.

Opioids

Important to understand potency differencesFentanyl>hydromorphone>oxycodone>morphine/hydrocodone>codeine

Side Effect ProfileNausea

Vomiting

Constipation

Confusion

Respiratory depression

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Medications Affecting Transmission

• NMDA antagonists• Methadone

• Ketamine

• Anticonvulsants• Sodium Channel Blockers

• Calcium Channel Blockers

• Lidocaine/mexilitine

• Opioids

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NMDA Antagonists

MethadoneUnique pharmacokinetic profileNeuropathic or mixed painHyperalgesia/allodynia

KetamineCan decrease opioid requirementNeuropathic or mixed painHyperalgesia/allodynia

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Anticonvulsants

Medication Recommended Starting Dose

Common Side Effects

Gabapentin 100-300mg QHS Drowsiness, dizziness, edema, fatigue

Pregabalin 25mg q12H

Topiramate 200mg Q12H Weight loss, agitation, kidneystones, glaucoma

Cabamazepine 50mg q12H Skin reactions, hepatotoxicity, hyponatremia, CNS depression

Valproic Acid 125-250mg BID or Q8H Drowsiness, dizziness nausea, thrombocytopenia, flu-like symptoms, tremor

Lidocaine/mexilitine

Sodium channel blockade

If lidocaine is tolerated, can switch to oral mexilitine

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Medications Affecting Modulation

Tri-cyclic antidepressants (TCA)

Serotonin and norepinephrine re-uptake inhibitor (SNRI)

Opioids

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TCA

Medication Recommended starting dose Common Side Effects

Amitriltyline 10mg QHS Anticholinergic, sedation, QT prolongation

Nortriptyline 10mg QHS Anticholinergic, QT prolongation, sexual dysfunction

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SNRI

Medication Recommended starting dose Common Side Effects

Venlafaxine 37.5mg daily Nausea. Insomnia or drowsiness

Duloxetine 60mg daily Headache, drowsiness, fatigue, nausea

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Effects of Untreated Pain

Untreated pain can…Alter neurotransmission signals

Modulate pain pathways

Make it more difficult to treat pain in the future

Lead to chronic pain condition

Other effects include…Endocrine/metabolic, respiratory, musculoskeletal, gastrointestinal and immunologic

Barriers

Practice Issue Barrier Potential Problems

Failure to use more than medications Miss benefits of physical, behavioral and psychological therapies to help re-train the central nervous system

Failure to target mechanism of pain Under-treated pain

Failure to treat neuropathic pain with adjuvants

Increased nervous system hypersensitivityUnder-treated pain

Reliance on short acting opioids Increased breakthrough, disturbed sleepOpioid tolerance

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References

1. Pasero, C. & McCaffery, M. (2011). Pain Assessment and Pharmacologic Management. St. Louis: Elsevier/Mosby2. International Association for the Study of Pain. IASP Pain Terminology. www.iasp-pain.org/terms-p.html

3. Whitten CE, Donovan M, Cristobal K. Treating Chronic Pain: New Knowledge, More Choices

4. Backonja M. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA. 1998 Dec 2;280(21):1831-6.

5. Benzon, H et al. (2011) Essentials of Pain Medicine: Third Edition. Philadelphia, PA: Elsevier Saunders.

6. Caraceni A. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol. 2004 Jul 15;22(14):2909-17.

7. Challapalli V. Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003345.

8. Dworkin RH. Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003 Nov;60(11):1524-34.

9. Ferrini R, Paice JA. How to initiate and monitor infusional lidocaine for severe and/or neuropathic pain. J Support Oncol 2004;2:90-94.

10. Finnerup NB. Pain. Algorithm for neuropathic pain treatment: an evidence based proposal. 2005 Dec 5;118(3):289-305. Epub 2005 Oct 6.

11. Finnerup NB, Sindrup SH, JensenTS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010 Sep; 150(3):573-81.

12. Galer BS. Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. J Pain Symptom Manage. 1996 Sep;12(3):161-7.

13. Galluzzi KE. Managing neuropathic pain. J Am Osteopath Assoc. 2007 Nov;107(10 Suppl 6):ES39-48.

14. Gilron I. Neuropathic pain: a practical guide for the clinician. CMAJ. 2006 Aug 1;175(3):265-75.

15. Mao J, Chen LL. Systemic lidocaine for neuropathic pain. Pain. 2000;87:7-17. Melissa Vyvey. Steroids as pain relief adjuvants. Can Fam Physician. 2010 Dec; 56(12): 1295–1297.

16. Rowbotham M. Gabapentin for the Treatment of Postherpetic Neuralgia: A Randomized Controlled Trial. JAMA. 1998;280(21):1837-1842.

17. Tauben D. Nonopioid Medications for Pain. Phys Med Rehabil Clin N Am. 2015:26;219–248.

18. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004 Mar 16;140(6):441-51

19. www.med.ohio.gov

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