Resident Editors: Lulu Tsao, M.D., Jenna Nguyen, M.D., Irina, Kryzhanovskaya, M.D., Triveni Defries, M.D.,

Faculty Editors: Christy Soran, M.D., Scott Steiger, M.D., Michael Rabow, M.D.

BOTTOM LINE ✔ Careful evaluation of the etiology of pain is important to target therapy ✔ Discuss and set realistic expectations of pain management, with a focus on functional status ✔ Treating co-morbid conditions such as anxiety and depression can improve mood, sleep, fitness and mobility ✔ Obtain urine drug testing and pain contracts for patients at risk for opioid misuse. ✔ Assess level of risk, even for patients on maintenance therapy, to ensure appropriateness of pain treatment. ✔ Care plan should always include diagnosis, treatment goals and treatment plan.

Background

• Most common reason for seeking medical attention and is reported by 20-50% of patients seen in primary care.

• Pain of acute injury or illness usually resolves in a few weeks to months; conventional definition of chronic pain is pain lasting > 3 months or pain that persists beyond what is expected given degree of pathology
• Use a step-wise approach, including a focus on non-pharmacologic strategies.
• Multimodal pain treatment with a focus on pharmacologic, physical, alternative, and psychologic treatment of pain often works better than medications alone. Combination of opioids and neuropathic agents at lower doses often work better than monotherapy alone.
• Goals of pain management:
• Realistic goal setting based on function (not total elimination of pain)
• Goals are negotiated with the patient
• Anticipation and management of treatment side effects

Signs and Symptoms

Neuropathic (burning, stabbing, shooting)

• Peripheral nervous system: due to damage of peripheral nerve (postherpetic neuralgia, complex regional pain syndrome, metabolic)
• CNS: arises from abnormal CNS activity (phantom limb pain, post-stroke pain, spinal cord injury)

Nociceptive

• Somatic/Musculoskeletal (well localized but variable in description including aching, soreness, stiffness): musculoskeletal pain, mechanical/compressive pain
• Visceral (poorly localized, deep, dull, cramping, vague): pain arising from viscera mediated by stretch receptors such as pain with appendicitis, hepatomegaly, appendicitis
• Inflammatory (aching, swelling, erythema, heat): arthropathies, infection, post-operative pain, tissue injury

Mixed (combination of pain patterns)

Evaluation

• History and physical exam: specific pain disorders such as low back pain, fibromyalgia and neuropathic pain have been published, therefore establishing diagnosis is vital
• Pain evaluation and description: OPQRST (onset, palliation/provocation, quality, radiation, associated symptoms/severity, time course)
• Nature and intensity of pain
• Current and past treatments for pain
• Underlying and co-existing medical and mental health conditions
• Functional and social assessment: effect of pain on function (physical, occupational, psychiatric, etc.), history of substance use
• Complete physical exam, including detailed neurologic exam
• Directed blood testing when specific causes (rheumatologic, infectious, oncologic) suggested by H&P. Review imaging and avoid unnecessary radiation exposure.

Treatment: Non-Pharmacologic Therapies

• Nonpharmacologic therapies, along with nonopioid pharmacology therapy, are first-line options for chronic pain.
• Combining these approaches can lead to improvement in pain and functional status for a number of conditions, such as fibromyalgia and low back pain.
• Non-pharmacologic modalities require patient participation and motivation, and can improve physical mobility, fitness, mood, sleep, and general health.
• It is key to treat co-morbid conditions such as depression, anxiety, and sleep that commonly accompany chronic pain disorders.
• Consider referral for Integrative Medicine (at UCSF the Osher Center - http://www.osher.ucsf.edu/)[LT1] 
• Complementary and Alternative Medicine Resources:
• Free Chair Massage at the Wellness Center: 1st and 3rd Thursday of the month at 11am
• Free Acupuncture:
  • SFHP patients: call your insurance for access
  • HERC Wellness Center - in Bayview
  • Glide Memorial Church: 330 Ellis, Mon AM, Tues PM, Thurs PM, Fri 10-3p
  • Southeast Health Center Thursday 10-12pm
• Free Yoga
  • Wellness Center calendar
  • Yoga to the People, 16th & Mission
• Mindfulness Activity Handout: here and here
• Breathing Exercise Handout: here or here
• Relaxation Exercises Handout: here
• Medical Marijuana Form here
• Additional Resources here, and NICE COMPREHENSIVE GUIDE HERE from San Francisco Health Plan
• Cognitive and Behavioral Therapy Resources

1. Chronic Pain Group: 12 weeks, Monday afternoons at ZSFG. Refer via Behavioral Health Team.
2. Warm handoff to Behavioral Health in Clinic. Refer via Behavioral Health Team
   1. Short-term therapy
   2. Group classes, Eng & Span
3. Mental Health ACCESS line (all SF): 415-255-3737
4. Chronic Pain in 5 Minutes Video here, and with Spanish subtitles here
5. Chronic Pain Toolkit Video (9min) here
6. Sleep Hygiene handout here
7. Chronic Pain toolkits for patients here. Pain Flare plan here.
8. Tension Release handout, from Blue Walcer here
9. Ladies Night: Mission Neighborhood Resource Center, Thurs nights, free. 165 Capp (near 17th street)
10. RAMS Peer Support Wellness Center (Market and 9th, 1282 Market) - cooking, art, and exercise classes, free

EDUCATION: refer patients to the American Chronic Pain Association Website www.theacpa.org; chronic pain Facebook groups; Chronic Pain Toolkit by Peter Moore here. Intermountain Healthcare Guide (44p), but excellent here.

• Physical Modalities

1. Physical & Occupational Therapy
   1. One-on-one: eReferral
   2. Laguna Honda Aqua Therapy: eReferral
   3. Home-bound patient: Health at Home Referral: eReferral
   4. Back Class: eReferral
2. Healthy Spine Clinic: GMC and FHC patients. eReferral via Pain Clinic.
3. Physiatry Referral (botox, bracing): eReferral
4. Podiatry Appointment: patient calls 415-206-8494 to request an appointment (no referral necessary) for SFHN
5. Joint Injections
   1. Ortho Joint Injection Clinic (Wed AM): eReferral Ortho. Write “Referring for Joint Injection Clinic”
   2. Fam Med Procedures Clinic: eReferral Minor Procedures Clinic
   3. Knee Injection article & video
   4. Shoulder injection article & video
   5. Trigger Point Injection article, here & video
6. Orthotics Form, diabetic shoe form here
7. Exercise Programs
   1. Wellness Center calendar
   2. Simple Back Exercises handout here, or here (Kaiser)
   3. Salvation Army gym membership $25/mo. 240 Turk St (at Jones)

Treatment type	Options
Lifestyle	Tobacco cessation, weight loss, sleep hygiene
Physical	Exercise, physical and occupational therapy, heated pool therapy, stretching and yoga, podiatry referral, orthotics, transcutaneous electric nerve stimulation (TENS), spinal manipulation (caution with cervical spine), trigger point injections, steroid injections and nerve blocks
Psychological	Treatment of underlying mental health disorders (depression, insomnia, or anxiety), biofeedback, cognitive behavioral therapy (CBT), counseling, music, relaxation, chronic pain groups, patient education (e.g. the American Chronic Pain Association: www.theacpa.org)
Complementary and alternative	Mindfulness, acupuncture, herbal remedies, massage, reflexology, medical marijuana

Low back pain¹:

	Moderate-quality evidence	Low-quality evidence
Acute or subacute low back pain	Superficial heat	Massage, acupuncture, spinal manipulation
Chronic low back pain	Exercise program, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction	Tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, CBT, spinal manipulation

Injections²:

• Nonradicular back pain: insufficient evidence for facet joint and epidural steroid injections (ESI)
• Herniated lumbar disc: shared decision-making around ESI as an option, with potential short-to-moderate term benefit and lack of long-term benefit. Surgical referral for persistent and disabling pain.
• Spinal stenosis: insufficient evidence for ESI. Surgical referral for persistent and disabling pain.

References:

¹Qaseem A, Wilt TJ, McClean RM, et. al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med. 2017;166(7)493-505.

²Chou R, Loeser JD, Owens DK, et. al. Interventional Therapies, Surgery, and Interdisciplinary Rehabilitation for Low Back Pain. Spine 2009; 34(10):1066-1077.

Treatment: General Principles of Chronic Cancer Pain

As with any pain, assess the type of pain (nociceptive, neuropathic, inflammatory). In cancer patients, it is also important to identify cancer pain syndromes and to evaluate whether pain is disease-related, treatment-related, or neither.

• Recognize that a change in pain might indicate a serious new complication, e.g. spinal cord compression from a metastasis requiring XRT
• Common pain syndromes may be due to the cancer itself (bone pain from metastases) or treatment (mucositis, chemotherapy-induced neuropathy)

The WHO’s pain ladder is meant to address cancer-related pain. It consists of the following steps, with escalation to the next step if the patient has unrelieved pain:

• Step 1: for mild pain, start with a non-opioid medication with or without adjuvant therapy
• Step 2: for moderate pain, start a mild opioid or low dose of a more potent opioid, with or without non-opioid medication and/or adjuvant therapy
• Step 3: for severe pain, start a more potent opioid, with or without non-opioid medication and/or adjuvant therapy

Adjuvant therapies for specific pain types:

• Bone pain: NSAIDs, corticosteroids, bisphosphonates, RANK-L inhibitors, radiation and radionuclides, vertebroplasty/kyphoplasty
• Neuropathic pain: corticosteroids, anti-convulsants (gabapentin/pregabalin), SNRIs, tricyclic antidepressants, cannabanoids
• Bowel obstruction: need for NG tube; consider corticosteroids, metoclopramide, anticholinergic agents, and stenting

Other adjuvant therapies include topical agents (e.g. capsaicin, lidocaine), surgical intervention (when possible), disease-modifying treatment, interventional anesthetic techniques (e.g. nerve blocks), TENS, complementary and alternative medicine, and addressing psychological, emotional, social and financial distress.

Treatment of chronic pain in cancer survivors follows similar guidelines for chronic pain overall, with specific attention to whether new-onset pain could represent recurrent disease, second malignancy, or new-onset treatment effects.

References:

Abrahm JL. A Physician’s Guide to Pain and Symptom Management in Cancer Patients, 3^rd ed. Baltimore: Johns Hopkins University Press, 2014.

Paice JA, Portenoy R, Lacchetti C, et. al. Management of Chronic Pain in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016; 34:3325-3345.

Treatment: General Principles of Chronic Non-Cancer Pain (CNCP)

There is weak evidence that opioids reduce chronic non-cancer pain, yet they are increasingly being prescribed with the use of opioids for musculoskeletal complaints doubling from 1980 to 2000. Chronic pain is often part of a complex syndrome that includes other bio-psychosocial factors. A care plan for patients with chronic pain should be documented to cover the following:

• Diagnosis: what specific condition is the patient being treated for
• Treatment goals:  specify ways to maximize patient’s quality of life, functional status, minimize the side effects of pain medication, and target specific functional goals as identified by the patient in his/her own words.
• Treatment plan: teach patients how to maintain a healthy lifestyle with specific action items addressing proper nutrition, sleep hygiene, regular physical activity and stress reduction techniques; document risk/benefit discussion; outline medication plan; provide follow-up instructions

New patients: Primum non nocere (“first, do no harm”)

General rules:

• No opioids for CNCP at first visit to clinic, and no new opioids at first visit with you as new provider
• Trial non-opioid analgesics such as acetaminophen and NSAIDs
• NSAIDs are indicated for mild to moderate somatic pain.  Some compounds are indicated for severe pain. Consider switching NSAIDs if pt unable to tolerate or does not respond to a particular NSAID.
• Avoid NSAIDs in the elderly
• Consider celecoxib for pt who require chronic NSAIDs and are at risk for gastropathy (though doses > 200 mg/day associated with increased risk of CV risk)
• Adverse effects of NSAIDs:
  • Relative contraindication in pt at high risk for PUD (advanced age, history of PUD or prior NSAID gastropathy, bleeding diathesis, steroid use) and pt with CV disease
  • GI side effects including dyspepsia (food, antacids, PPIs may help patient’s tolerate NSAIDs)
  • Nephrotoxicity
• Perform risk assessment to identify those at increased risk of poor outcomes with opiate use (assess risk of substance abuse, addiction, family history of abuse)
• Review and sign treatment agreement with urine drug testing before initiating opioids
• Obtain permission to discuss care with all psychiatric and medical providers
• Maximum prescription for 28 day supply to facilitate refills, visits, and avoid weekend problem
• Consider identifying one family member or partner NOT on opioids with whom patient allows communication regarding treatment

APEX tip: consider using dotphrases “.painchecklist” or “.opiodchecklist” for helpful reminders

Assess (Potential) Benefits:

• No measures have been demonstrated to predict a good response
• Reserve for pt with moderate to severe chronic pain with adverse impact on function or quality of life
• Thoroughly (re)assess cause of pain:
  • Make a diagnosis before initiating opioids (e.g. lumbago, headache, fibromyalgia do not improve, and may worsen w/ chronic opiates)
  • Trials of multiple non-pharmacologic treatments before opioids
  • Trials of multiple non-opioid medications before opioids
• ID and document a functional goal before initiating opioids
  • “Work ___ hours weekly, exercise ___ hours weekly…”
• ID and document a pain control goal before initiating opioids
  • e.g. move from a “7” on average to a “4” on analog pain score
• Initiate with short-acting low dose and titrate upward until goal is achieved or side effects limit further dose escalation
• Amount of opiate used in 24 hours can then be converted to sustained release form with breakthrough pain treated with short-acting drugs

Assess Patient’s Level of Risk:

• Use a validated tool for assessing risk of aberrant behaviors, including using more than prescribed, requesting early refills, abusing other drugs, lost/stolen prescriptions. 
  • Webster’s opioid risk tool (http://www.opioidrisk.com/node/887). Low risk (0-3 pts): 91% will NOT display aberrant behavior. High risk (>8 pts): 95% WILL display aberrant behavior.
• Review medication list for interactions or concerning combinations
  • Other sedating or respiratory suppressive medications, particularly benzodiazepines, can increase risk of harm
  • Methadone levels affected by multiple CYP-inducing/inhibitors
• Review labs/PMH for any contraindications
  • Morphine contraindicated in CrCl < 30 due to active metabolite
• Review patient’s ability to store medication safely
  • Ingestion by opioid naïve children or others can be fatal
• Obtain thorough urine toxicology testing (ex: drugs of abuse, oxycodone screen, opiate confirmation, urine methadone) at first several visits
• No increase in dose more frequently than q2wks

Maintenance patients

Reassess ongoing benefits and adverse effects– just because it used to work, does not mean it still does

• Document pain score and progress to functional goal at every visit (at least q 6 months)
• Document last dose of each medication EVERY visit
  • Quick assessment of need, helps interpretation of toxicology

Reassess risk profile

• Lost prescription or medication = high risk to community (and patient)

• Frequent toxicology testing
  • Q1mo (at least) for any aberrant behavior, dose above equivalent of morphine 100 mg (http://opioidcalculator.practicalpainmanagement.com/)
  • Q12mo acceptable only in stable, low dose, low risk patient
• Consider occasional pill count visit with RN 1-2 weeks after MD visit; this is especially useful for high dose patients
• Mitigate risks! 
  • Refer/communicate with psychiatrist, social worker, substance abuse treatment
  • Involve family member(s) early and often

When problems arise (early refill request, lost medication, +utox, increased side effects):

• Increase monitoring
  • More frequent urine toxicology testing
  • More frequent visits
  • PILL COUNT VISIT
  • Discuss with patient in risk/benefit terms!
• Refer for more help: social work, substance abuse treatment, psych

When to refer to a pain specialist

• Debilitating symptoms or loss of functioning
• Symptoms located at multiple sites
• Symptoms that do not respond to initial therapies
• Escalating need for pain medication

Tapering: when risks > benefits (aberrant behaviors, intolerable side effects, lack of progression toward therapeutic goals)

General rules

• Write EXPLICIT instructions: useful for patients and providers.
• Consider writing weekly prescriptions; drawback may be multiple copays given multiple prescriptions.
• If multiple agents, convert to morphine equivalents to calculate total dose.
• Reduce long-acting agents first, as long as short-acting agents are limited in number.
• Remember, opiate withdrawal may be physically unpleasant but it is not life threatening!

Slow taper  (minimizes withdrawal symptoms)

Indications: no evidence of benefit, high doses, multiple high-risk behaviors

• Go slow and consider removing 10% of original dose per month in an incremental fashion
• Consider changing formulation of short-acting opioid to a lower dose formulation and reducing daily dose by 1-2 pills each week
• Can convert long-acting opioid to lower dose formulation as well

Rapid taper 

Indications: substance abuse, loss of control over pill use

• Remove 10-15% per week
• Use the urine drug screen as an opportunity for substance abuse counseling and referral

Immediate cessation

Indications: overdose, suicide attempt, prescription forgery, diversion, physical assault or threat to provider or staff

• Add flag to patient’s chart and update problem list with explicit reasons

Consider using the following to help manage withdrawal symptoms:

• Clonidine (hypertension, tremors, sweats, anxiety)
• Hydroxyzine or diphenhydramine (anxiety, restlessness, insomnia)
• Phenergan or metoclopramide (nausea)
• Tums, milk of magnesia (dyspepsia)
• Acetaminophen (pain, fever)

Treatment: Opiate Prescribing

• Chronic somatic/neuropathic pain (i.e. MSK pain, peripheral neuropathy, post-herpetic neuralgia) is usually more responsive to opioids than visceral/central pain syndromes (i.e. abdominal/pelvic pain, fibromyalgia, HA’s).
• For moderate to severe chronic daily pain, around-the-clock long-acting opioids preferred over short-acting prn meds only.

• Common opioid side effects: constipation, nausea/vomiting, pruritis, sedation, blood pressure instability (uncommon), opioid-induced hyperalgesia, narcotic bowel syndrome (constipation is the only side effect that usually persists despite ongoing use, so daily bowel regimen is critical).

• Obtain pain contracts and or urine drug testing for patients who are: at risk for abuse/misuse (personal or family history of drug/alcohol abuse, mental health co-morbidities), exhibiting aberrant behaviors, getting care from multiple MDs.
• One technique for obtaining screening urine toxicology tests in clinic is to work with the medical assistant (MA): the MA will hold the narcotic script until the patient provides a urine sample, and if the patient cannot provide a urine sample then s/he cannot receive their prescription for controlled substances.
• Tools for screening high-risk patients: Screener and Opioid Assessment for Patients with Pain (SOAPP^®) at www.painedu.com/soap.asp, or Webster’s opioid risk tool as above (accessed April 30, 2013).

Medication	Typical Dosing	Dosing Interval	Max dose q24h	Comments	Adverse Effects
Selected Non-Opioid Analgesics (class)
Acetaminophen	500-1000 mg	4h	3 gm (2 gm if  liver disease)	Consider as 1st line in OA	Liver toxicity at high doses
Ibuprofen (NSAID)	400-800 mg	6h	2400 mg	Especially good for inflammatory conditions, bony pain, consider PPI if mod-high risk GI toxicity, cardiac toxicity	GI upset, GI bleeding, plt dysfunction, nephrotoxicity, cardiac toxicity
Naprosyn (NSAID)	500 mg initially, then 250 mg	12h	1500 mg	Same as for Ibuprofen, but likely less cardiac toxicity	Same as for Ibuprofen, except less cardiac toxicity
Celecoxib (NSAID)	100-200 mg	12h	200-400 mg	Doesn’t interfere with platelet aggregation	Risk of cardiovascular events
Tramadol	25-50 mg	4-6h	400 mg (300 mg in elderly)	Has weak affinity for mu receptor	HA, confusion, sedation, nausea
Selected Co-Analgesics (class)
Gabapentin (anticonvulsant)	Titrate q3 days from 100-300 mg qhs	TID	No upper limit	Use for neuropathic pain; Adjust if renal disease; very few drug-drug interactions, minimum effective dose 900 mg total/day	Dizziness, sedation
Duloxetine (SNRI)	30-60 mg	Daily	60 mg	Use for neuropathic pain, also FDA approved for chronic MSK pain. SNRI Venlafaxine has similar effects	Nausea, dry mouth, insomnia, drowsiness, constipation, fatigue, dizziness
Nortriptyline (TCA)	10-75 mg	Daily	300 mg	Effects neuropathic pain at lower doses than for depression (i.e. 1-3 days vs weeks); all TCAs seem effective	Anti-cholinergic side effects (highest with Amitriptyline so would avoid)
Baclofen (Skeletal muscle relaxant)	5-10 mg	TID	120 mg	Helpful for muscle spasm as well as neuropathy; other agents in class include Cyclobenzaprine and Carisoprodol (latter has high abuse potential)	Sedation, dizziness, abuse potential.  Benzodiazepines may be just as effective for spasm.
Lidocaine patch (Local anesthetic)	5% patch applied to area of pain	BID	1-4 patches at a time	Not all insurances cover, also available as a gel or cream; other somewhat effective local anesthetic is Capsaicin cream	Skin irritation, contact dermatitis

Opioid (by increasing potency)	Parenteral Route	Oral Route	Starting Dose for Opioid Naive	Breakthrough Pain If using SR opioids ATC, rx IR opioid for breakthrough pain. Breakthrough dose is 10-15% of the 24h total daily opioid dose, available q1-2h.   If using 3 or more rescue doses daily, consider increasing ATC dose.
Oxycodone IR: Oxycodone SR: Oxycontin	N/A	20 mg	5 mg IR, 10 mg SR
Morphine IR: Morphine, Roxanol SR: MS Contin, Kadian	10 mg	30 mg	15 mg for both IR and SR formulations	Opioid Conversions Calculate 24h total opioid dose Convert to desired opioid (equivalent 24h dose) using equianalgesic table to left. Divide 24h dose of new opioid by the number of doses given per day. Reduce calculated dose of new opioid by 25% -50% for incomplete cross-tolerance; titrate up as needed.
Hydromorphone (IR only)	1.5 mg	7.5 mg	2 mg
Fentanyl IR: Actiq SR: Patch	0.1 mg	N/A	25 mcg patch = 50-100 mg oral morphine q24h

• Combination drugs such as Codeine/Acetaminophen (Tyco), Hydrocodone/Acetaminophen (Vicodin, Lortab) or Oxycodone/Acetaminophen (Percocet) are available, but caution given risk of liver toxicity with high doses of Acetaminophen.
• Methadone may be considered for chronic pain, however given higher rates of death (1/3 of opioid-related overdose deaths although it represents only 10-15% of all the opioids prescribed) would use only in consultation with Palliative Care, Pain Management, or in the setting of a treatment program.

 

References

Arnold R, Weissman DE. Calculating Opioid Dose Conversions, 2nd Edition. Fast Facts and Concepts. July 2005; 36. Available at: http://www.eperc.mcw.edu/fastfact/ff_036.htm.

Berland D, Rodgers P. Rational use of opioids for management of chronic nonterminal pain. Am Fam Physician 2012 Aug 1; 86(3):252-6.

Carville et al. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis. 2008 Apr;67(4):536-41.

Group Health Cooperative. Chronic Opioid Therapy Safety Guideline for Patients With Chronic Non-Cancer Pain. 2012. Available at: http://www.ghc.org/all-sites/guidelines/chronicOpioid.pdf. Accessed May 17, 2013.

Institute of Medicine. Relieving Pain in America. National Academy of Sciences. June 2011. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2011/Relieving-Pain-in-America-A-Blueprint-for-Transforming-Prevention-Care-Education-Research/Pain%20Research%202011%20Report%20Brief.pdf. Accessed May 23, 2013.

Jackman et al. Chronic nonmalignant pain in primary care. Am Fam Physician. 2008 Nov 15:78(10):1155-62.

Meldrum M. The ladder and the clock: cancer pain and public policy at the end of the twentieth century.

 J Pain Symptom Manage 2005; 29(1):41-54. 

Webster LR and Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the opioid risk tool. Pain Medicine 2005;6(6):432-442.

Alford DP et al. Update in pain medicine. J Gen Intern Med. 2008;23(6):841

Warner, EA. Opioids for the Treatment of Chronic Noncancer Pain. Am J of Med. 2012;125,1155-1161