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Improving Strategies for the Management
and Treatment of Chronic Pain
Eric S Hsu, M.D.
Clinical Professor Pain Management Center Department of Anesthesiology David Geffen School of Medicine at UCLA
Definition of Pain, Allodynia, & Hyperalgesia
- Pain: “ An unpleasant sensory and emotional
experience associated with actual or potential
tissue damage, or described in terms of such
damage.”
- (Merskey and Bogduk. Classification of Chronic Pain. 1994. IASP)
- Allodynia : painful response to a non-painful stimulus
- Hyperalgesia : heightened response to painful stimulus
Chronic Pain, Sleep Disturbances, and Depression/Anxiety
Depression/
anxiety
Chronic pain
Nicholson B et al. Pain Med. 2004;5(suppl 1):S9-S.
Sleep
disturbances
Optimal
functionality
Mixed Type
(eg, Trauma, postoperative pain, cancer pain, chronic back pain & sciatica)
Common Pain Syndromes
Nociceptive
Pain
Neuropathic
Pain
Visceral Abdominal Obstetrical
Head Headache Orofacial
Postherpetic Neuralgia
Postoperative Cancer Pain
CRPS
CRPS = complex regional pain syndrome.
Central Poststroke Pain
Trigeminal Neuralgia
Distal Polyneuropathy (eg, diabetic, HIV)
Musculoskeletal Osteoarthritis Rheumatoid Arthritis Low Back Pain
Mixed Type Postoperative Cancer Pain
Interventions for Chronic Pain Management
Diagnostic & Therapeutic Approach
- Peripheral, neuraxial nerve and sympathetic blockade
- Epidural Steroid Injection
- Herniated disk, nerve root irritation
- Discogenic pain e.g. annulus tear
- Spinal stenosis or foraminal stenosis
- Facet Injection, Medial Branch Block and Radiofrequency Ablation
- Facet joint arthropathy
- Medial branch and posterior musculoskeletal structures
- Joint & bursa injection: facet, sacroiliac joint, knee, hip or other joints
- Neuromodulation: Spinal Cord Stimulation (SCS) or Spinal Infusion Therapy
Classification of NSAIDs
Chemical/Pharmacokinetic Subclasses
- Low potency/fast elimination
- High potency/fast elimination
- Intermediate potency/elimination
- High potency/slow elimination
- Salicylates : aspirin, salicylic acid
- Propionic acid: ibuprofen
- Anthranilic acid: mefenamic acid
- Propionic acid: ketoprofen
- Pyrrolizine carboxylate: ketorolac
- Phenylacetic acid: diclofenac
- Indoleacetic acid: indomethacin
- Salicylates : diflunisal
- Propionic acids : naproxen
- Naphthylalkanone: nabumetone
- Oxicams : meloxicam, Piroxicam
NSAIDs & COX-2 Selective Inhibitor in Chronic Pain Medicine Key Clinical Pearls
- Clinical data have shown COX-2 selective inhibitors offer the similar pain relief as Non-specific NSAIDs - COX-2 inhibitors have a better GI safety profile vs Non- specific NSAIDs up to 6 months - Overall safety is similar among all NSAIDs - Avoid COX-2 inhibitors & NSAIDs in patients with CV risk & those requiring aspirin - Use lowest dose and shortest duration for all NSAIDs
- All NSAIDs including COX-2 inhibitors possess potential risk for Cardiovascular or cerebrovascular thromboembolic events
Parenteral NSAID: Ketorolac (Toradol)
in Pain Management
- A potent analgesic but only a moderately effective anti-inflammatory drug (mainly a COX-1 inhibitor & minimal COX-2 inhibitor)
- No tolerance, withdrawal, or respiratory depression (vs. opioids)
- Achieving peak plasma concentration in 30-50 minute
- Elimination half life of 4-6 hours
- The rate of elimination is reduced in elderly & in renal failure.
- Inhibit platelet aggregation & promote gastric ulceration, renal, cardiovascular & other systemic side effects
- Recommend to start with loading dose of 30 mg, then use 15 mg q 6 hours around the clock up to 2 days
- or 15 mg q 6 hours as needed up to 4 days
Afferent Sensory & Descending Modulatory Pathways Cousins & Bridenbaugh’s “Neural Blockade”, 4 th^ edition, Chap 31, Lippincott Williams & Wilkins 2009
PHN & DPN: Pharmacologic Treatment
FDA Approved Label Use for Neuropathic Pain
- Agents with consistent efficacy demonstrated in multiple, randomized, controlled trials for PHN^ (Postherpetic Neuralgia): - Topical agent : 5% Lidocaine patch - Gabapentin (Neurontin), Pregabalin (Lyrica)
- Consider safety and tolerability when initiating treatment with off label agents e.g.TCA, other anti-epileptics, and opioids
- Agents with consistent efficacy demonstrated in Painful DPN (Diabetic Polyneuropathy):
- Duloxetine (Cymbalta) & Pregabalin (Lyrica),
Tapentadol (Nucynta)
Cymbalta (Duloxetine) & Savella (Milnacipran)
SNRI in Pain Management
- Cymbalta (duloxetine hydrochloride) Delayed-Release Capsules
- Diabetic Peripheral Neuropathic Pain & Fibromyalgia
- Recommended dose for Cymbalta is 60 mg once daily.
- There is no evidence that doses > 60 mg confer additional significant benefit and the higher dose is clearly less well tolerated
- Start with a lower dose and titrate
- Since diabetes is frequently complicated by renal disease, a lower starting dose and gradual increase in dose should be considered for patients with renal impairment
- Savella (Milnacipran) Tablets indicated for the management of fibromyalgia. Initial U.S. Approval: 2009Recommended dose is 100 mg/day
- May be increased to 200 mg/day based on individual patient response
- Dose should be adjusted in patients with severe renal impairment
Tri-cyclic Antidepressants in Pain Management
Common Adverse Events
(generally anticholinergic ):
- Blurred vision
- Cognitive changes
- Constipation
- Dry mouth
- Orthostatic hypotension
- Sedation
- Sexual dysfunction
- Tachycardia
- Urinary retention
- Desipramine
- Nortriptyline
- Imipramine
- Doxepin
- Amitriptyline
Fewest AEs
Most AEs
Beers MH. Arch Intern Med. 1997;157:1531-1536; Mackin GA. J Hand Ther. 1997;10:96-109; McCue RE. Clin Geriatr Med. 1992;8:323-334.
AEs = adverse events
Cancer Pain Management
Comprehensive Evaluation and Treatment
♫ Cancer pain-related history, reports and physical exams
♫ Working diagnosis and cancer pain management
♫ Progressive diagnosis and evaluation
♫ Problem list development and treatment plans
♫ Time contingent & efficient approach in cancer pain
♫ We need patient’s & family’s feedback regarding ongoing treatment
WHO Three Step Analgesic Ladder
Guideline for Cancer Pain Management
1. Non-opioid analgesics & adjuvant meds
2. Weak opioid analgesics plus 1
st
step
3. Strong opioid analgesics plus 1
st
nd
- Addendum: transdermal delivery, subcutaneous or IV PCA
- Neuraxial drug delivery system, Neuromodulation, Nerve block, Neurolysis (chemical or radiofrequency ablation)
Cancer Breakthrough Pain Management
- The Transmucosal Immediate Release Fentanyl ( TIRF ) Risk Evaluation and Mitigation Strategy ( REMS ) program is an FDA-required program
- It’s designed to ensure informed risk-benefit decisions before initiating treatment, and while patients are treated to ensure appropriate use of TIRF medicines.
- TIRF medicines are indicated only for the management of breakthrough pain in adult cancer patients 18 years of age and older who are already receiving and tolerant to around-the-clock opioid therapy for their underlying persistent cancer pain.
- A list of TIRF medicines
- Oral transmucosal lozenge
- Buccal tablet, soluble film
- Sublingual tablet, spray
- Nasal spray
Pain Medication Treatment Agreement
Universal Precaution
- Pain Medication is responsibility of the patient
- No illicit substances are allowed
- Only one healthcare provider prescribes pain medications
- Unannounced drug screens can be enforced in follow up visit
- Periodically assess the 4A’s:
- -Analgesia
- -Activities of daily living
- -Adverse effects
- -Aberrant drug-related behavior
Treatment of Opioid-Induced Constipation
- US Food and Drug Administration (FDA) (9-16-2014) approved Naloxegol (MOVANTIK) tablets as the first once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) medication for the treatment of opioid-induced constipation (OIC), in adult patients with chronic, non-cancer pain. Naloxegol is expected to be available to patients in the first half of 2015.
- Lubiprostone (AMITIZA) 24 mcg capsules twice daily is FDA approved to treat Chronic Idiopathic Constipation (CIC) in adults. "Idiopathic" means the cause of the constipation is unknown and not due to an underlying illness or medication.
- Lubiprostone 24 mcg twice daily is also approved to treat constipation caused by opioids, a type of prescription pain medicine, in adults with chronic, non-cancer pain.
- Lubiprostone 8 mcg capsules twice daily is approved to treat Irritable Bowel Syndrome with Constipation (IBS-C) in women 18 years of age and older.
- Lubiprostone is a chloride channel activator. Initial US approved in 2006.
Diagnosis & Treatment of Low Back Pain (LBP)
- A Joint Clinical Guideline from American College of Physicians & American Pain Society provide evidence-based information on LBP
- First-line medication for LBP: Acetaminophen, NSAIDs
- Nonpharmacological therapy with proven benefits for LBP
- 1. Acute LBP : spinal manipulation
- 2. Sub-Acute LBP or Chronic LBP
- intensive interdisciplinary rehabilitation, exercise therapy, acupuncture, massage therapy, spinal manipulation, yoga, cognitive-behavioral therapy (CBT), relaxation and biofeedback
Chou R, Qaseem A, Snow V, Casey D, Cross JT, Shekelle P, Owens DK; Ann Intern Med. 2007 Oct 2; 147(7): 478-
National Institutes of Health (NIH)
Consensus Statement on Acupuncture in 1997
- NIH organized a conference of panel of experts to evaluate the available literature on acupuncture in 1997
- While designing studies to evaluate efficacy remain a challenge, Acupuncture(AP) was widely practiced in the USA for treatment of
- Postoperative, & chemotherapy nausea and vomiting; and postoperative dental pain
- Other promising results of AP have been seen in
- headache, low back pain, asthma, menstrual cramps, fibromyalgia, and myofascial pain.
- NIH Consensus Conference. Acupuncture. JAMA 1998; 280:1518-
- Acupuncture. NIH Consensus Statement. 1997 Nov 3-5;15(5):1-
Comprehensive Pain Management: Summary
Gender & cultural differences
Address co-morbid conditions
Improve daily activity & function
Universal precaution for analgesics
Consider interventional approach
Complementary & Alternative Treatment
Better
Quality
of Life
