INTRODUCTION

Definition

Categories

Pain is a sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

1. Nociceptive pain: originates from the damaging tissues other than peripheral and central nervous system, such as joint pain and muscular pain.

       

2. Neuropathic pain: originates from injury to the nervous system, in the absence of noxious stimulation, such as trigeminal nerve pain, diabetic neuropathic pain, etc.

       

3. Mixed type of above: Such as lower back pain and cancer pain.

 

SOCIAL IMPACT OF PAIN

1.  30% of the population of developed countries suffered from chronic pain

2.  In United States:

  • 70 million people report chronic pain

  • 31 million people have chronic lower back pain

  • 20-50 million people suffer arthritis

  • 70-80% of the population suffers from head pain at least once per month

 

MAKING AN ACCURATE PAIN DIAGNOSIS

Methodology of making the correct diagnosis

  1. Obtain a detail and thorough pain history.

  2. Complete a meaningful physical exam that may apply skills in physical medicine and rehabilitation, sports medicine, neurology and physical therapy.

  3. Make a list of differential diagnosis and the presumably primary diagnosis.

  4. Complete the necessary laboratory and imaging investigations.

  5. Confirm the diagnosis.

  6. Allow enough time for patients to ask questions

 

PAIN CARE CHECKLIST

  1. Make sure the pain doctor spends enough time to listen to your pain story.  Because you pay for the service, it is your right to request the full time slot you suppose to have with the practitioner, if the pain history is too complicate and the time is not enough, make another appointment.

  2. Make sure your doctor has done the necessary physical exam before giving you the most possibly accurate diagnosis.  You can request a brief exam in each follow-up visit to ensure the diagnosis is still the same and correct.

  3. When the diagnosis is unclear, you can request some symptomatic treatment while waiting for more investigations.

  4. Common investigations in pain management include X-ray, CT, MRI, nerve conductive velocity (NCV) and electromyography (EMG).

  5. Make sure your doctor really knows your pain and give you a tentative plan for your treatment at the end of the visit.

  6. If a reasonable time (4-6 weeks) is given, and your doctor is still not sure of your diagnosis, request a referral for the second opinion. A doctor cannot know anything, but it is always right to refer patients to the specialists who may know how to treat.

  7. If one medication can solve the problem, avoid the second one.  Give yourself enough time to try on the medication before considering adding or switching to another medication.

  8. Comply to the treatment plan, if you have puzzles, always call your doctor.

  9. Report to your doctor and discuss any possible modification if no improvement after 2-4 weeks of treatment.

  10. Ask your doctor to review the medication regiment after 2-3 months of treatment, some medications may no longer be needed after the acute symptoms are under control.  Always alert yourself that almost all the medications have some side effect.

  11. Reasonable office or operating-room interventions can often abort the pain immediately; this can “buy” time for the medications to kick in.

  12. Consider complementary or alternative medicine such as acupuncture, herbal medicine if necessary.  Acupuncture has both laboratory and clinic data to support its use in pain management.  Please visit our acupuncture section for more information.

  13. A comprehensive treatment program is always the best.  This program should include pain specialists in anesthesiology/neurology/physical medicine and rehabilitation, pain psychology, pharmacy, physical therapy, alternative medicine (acupuncture, herb, nutrition, biofeedback, mediation or breathing exercise).

  14. Make sure you have been given necessary or enough visits for the diagnostic or treatment follow-up.

  15. If you are labeled as psychological pain sufferer and you don’t think you are, request a second opinion or explain it to the pain psychologist.  An experienced pain specialist maybe able to find out the “real” organic cause(s).

  16. No patient is entitled to suffer the under-treated pain. You are always right and responsible to look for the best treatment option.

  17. Be optimistic, and always have a hope to solve or relieve the pain.

  18. In most of the situations, consider the nonsteroidal anti-inflammatory drugs (NSAIDS) as the first-line treatment.

PAIN MEDICATIONS

Nonopioid Analgesics

Drug therapy is the mainstay of management of acute and chronic pain, including cancer pain.  The common pain medications can be classified into three categories: 1) Nonopioid analgesics; 2) opioid analgesics; 3) coanalgesics.

 1. Acetaminophen /Tylenol

        (1) Mechanism: possible inhibitor of cyclooxygenase (COX)-3 in the central

              nervous system

        (2) Advantage: does not affect bleeding, platelet aggregation and stomach mucosal

              integrity. Safe and may be first-line drug for elderly group.

        (3) Caution: limited to < 4 g per day.  No anti-inflammatory effect. Report of over-

              anticagulation with warfarin / coumadin.

2. Salicylates

        (1) Acetylsalicylic acid / Aspirin

             i.  Mechanism: inhibition of prostaglandin synthesis producing analgesic, anti-

                 inflammatory, antipyretic effects.

             Ii.  Advantage: cardiac protection, thromboembolic prophylaxis, stroke

                  prevention. Less used for pain nowadays

             Iii. Caution: gastric disturbances and prolongation of bleeding time.

                  Salts / Choline magnesium trisalicylate, trilisate

        (2) Salts / Choline magnesium trisalicylate, trilisate

              i.   Mechanism: same as above

              Ii.  Advantage: does not affect the platelet aggregation and bleeding time

              Iii. Caution: gastric irritation.

3.  Nonsteroidal anti-inflammatory drugs (NSAIDS)

        (1) Non-selective NSAIDS

              I.  Mechanism: inhibition of both COX-1 and COX-2 pathway, centrally and

                  peripherally, and thus production of prostaglandin.

              II. Advantage: first line drug in nociceptive pain such as musculo-skeletal pain

                  and cancer pain.  Rich in clinical experience.

              III. Caution: reversible increase of bleeding time or inhibition of platelet

                   aggregation, inhibition of renal effects.

              IV. Common drugs

  • Ibuprofen (Motrin): high incidence of GI and CNS side effects.

  • Naproxen (Naprosyn, Aleve)

  • Ketoprofen (Orudis)

  • Indomethacin (Indocin, Indocin SR)

  • Sulindac (Clinoril)

  • Etodolac (Lodine)

  • Ketorolac (Toradol): limit treatment to 5 days

  • Diclofenac (Cataflam)

  • Meloxicam (Mobic)

  • Piroxicam (Feldene)

  • Nabumetone (Relafen): fewer GI side effects

        (2) COX-2 selective NSAIDS

I.  Mechanism: selective inhibition of COX-2, but not COX-1 pathway.

II. Advantage:

1. Sparing the COX-1 effect provide the safety advantage to GI mucosal integrity and platelet aggregation function / bleeding time.

2. First line drugs for chronic pain such as rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis.

3. First line drugs for mild-to-moderate acute and intermittent pain including cancer pain and pain in elderly group.

4. Adjuvant drug for severe pain.

5. Short-term or intermittent use in patients with bleeding disorders or high risk of peptic ulcer disease (> 65 yr old, prior GI bleeding

episodes).

6. Used perioperatively, and in situations in which bleeding is concern.

III. Caution: no safer than non-selective NSAIDS in kidney toxicity.

IV. Common drugs

  • Celecoxib (Celebrex): safer for chronic use ( > 6 weeks)

  • Rofecoxib (Vioxx): for sulfa-allergic patients, longer T1/2

  • Valdecoxib (Bextra): probably more potent for acute pain

  • Parecoxib: will be in USA market this fall, prodrug of valdecoxib, for the parenteral use.

Opioid Analgesics

1. Mechanism: binding to specific receptors or the Mu and Kappa types in the central and peripheral nervous system.

 

2. Advantage: control of acute and severe pain; control of chronic pain including cancer pain and pain from sickle cell disease, with addition of nonopioids to the regiment.

3. Caution: Should only be used as a drug in the multidisciplinary treatment plan and not be used alone

Limit the use meperidine (Demerol, Pethidine) due to the risk of neurotoxicity.

Limit the use of mixed agonist-antagonists (especially Pentazocine / Talwin), due to the psychotomimetic effects.

d. Development of tolerance to: especially the first few days or weeks.

i.   Tolerance to analgesia

ii.  Tolerance to opioid-induced respiratory depression, somnolence, and nausea.

iii. Tolerance to opioid-induced constipation does not occur, and necessitates the use of stimulating laxatives along with chronic opioid therapy

iv. Development of physical dependence: withdrawn symptoms will occur if opioid is abruptly stopped.

1. Opioid abstinence symptoms: anxiety, irritability, chills alternating with hot flashes, salivation, watery eyes, running nose, over-

sweating, nausea, vomiting, abdominal cramps, diarrhea, and insomnia.

2. Appears from hours to days after cessation, depending on the half life of the drug.

Do not confuse physical dependence with opioid addiction: addiction is a drug seeking behavior, commonly involving selling and buying drugs on the street.

f.  Monitor the psychological state of the patient

i.  Patients appear to calm when the pain is well controlled

Ii. Patients appear anxious when the pain is not controlled.

g. Recognize and treat the side effects: sedation, constipation, nausea, vomiting, itching, and respiratory depression

i. Strategies:

1. Decrease the dose and increase the drug interval

2. Try a different opioid

3. Consider multidrug and multimodal therapy

4. Add another drug that counteracts the adverse effect

5. Change the way of giving the medication

 

4.   Common drugs:

(1) Morphine-like agonists (mu agonists)

  • Codeine

  • Morphine (MSIR, MS Contin, Oramorph SR, Kadian, Avinza)

  • Oxycodone (OxyContin)

  • Oxymorphone (Numorphan): Rectal suppository available

  • Meperidine (Demerol): neurotoxicity side effect, avoid in children

  • Propoxyphene (Darvon)

  • Hydrocodone

  • Hydromorphone (Dilaudid)

  • Methadone

  • Fentanyl: (Duragesic-transdermal, Actiq-oral transmucosal)

  • Levorphanol (Levo-Dromoran)

(2) Weak mu agonist-monoamine reuptake inhibitor

  • Tramadol (Ultram): lowers seizure threshold

  • Ultracet (Acetaminophen / Ultram)

(3) Mixed agonist-antagonist (kappa agonists): limited use due to serious psychotomimetic side effect

  • Pentazocine (Talwin):

  • Nalbuphine (Nubain): nasal spray available

  • Butorphanol (Stadol): nasal spray available

(4) Partial agonist:

  • Buprenorphine (Buprenex): avoid in labor

 

5. The way of administration:

  • Oral

  • Oral transmucosal

  • Transdermal

  • Oral transmu

  • Rectal suppository

  • Subcutaneous infusion

  • Intravenous infusion (including PCA)

  • Intramuscular injection

  • Epidural infusion

  • Intrathecal infusion

Opioid Analgesics

1. Tricyclic antidepressants

  1. Mechanism: Norepinephrine and serotonin reuptake inhibitor.  Enhancement of descending pain inhibitory function.

  2. Advantage: First line for neuropathic pain, enhancing the effects of opioids or NSAIDS, may be used in children with cancer-related pain.

  3. Caution:

    • Nocturnal orthostatic hypotension

    • Sedation

    • Dry eye and dry mouth

    • Worsening ventricular arrhythmias (contraindicated in coronary disease)

  4. Common Drugs

    • Amitriptyline (Elavil): probably most potent in TCA

    • Desipramine (Norpramin): least sedation

    • Nortriptyline (Pamelor): fewer side effects

    • Imipramine (Tofranil): potent and fewer side effects

2. Antiepileptic drugs

  1. Proposed mechanism:

  • Inhibition of ectopic, spontaneous firing of sensory neurons

  • Inhibition of glutamate transmission or glutamate receptors

  • Enhancement of GABA inhibitory function.

2. Advantage: important option for neuropathic pain, especially used for patients who cannot tolerate TCAs, and the pain shooting in quality.

3. Caution: various, such as sedation, extremity tingling and numbness

4. Common drugs

  • Gabapentin (Neurontin): Best studied and best tolerance.  Probably the most commonly used AED for neuropathic pain

  • Phenytoin (Dilantin)

  • Carbamazepine (Tegretol)

  • Oxycarbazapine (Trileptal)

  • Topiramate (Topamax)

  • Valproic acid / sodium valproate (depakote, depacon)

  • Tiagabine (Gabitril)

  • Levetiracetam (Keppra)

  • Lamotrigine (Lamictal)

  • Zonisimade (Zonegran)

3. Local Anesthetics

  1. Mechanism: stabilizing sensory neuronal membrane

  2. Advantage: topical dermal anesthesia

  3. Caution: not used in infected area

  4. Common drugs

  • Lidocaine 5% patches (Lidoderm): FDA-approved for postherpetic neuralgia

  • EMLA cream: mixture of local lidocaine and prilocaine

4. Glucocorticoids

  1. Proposed mechanism: Immunosuppression and anti-inflammatory action.

  2. Advantage:

  1. Manage acute and chronic cancer pain

    • Directly lyse lymphoma

    • Manage malignant lesions of the brachial or lumbosacral plexus when opioid is ineffective

    • Ameliorate nerve pain by reducing edema in tumor and nervous tissue

  2. Emergent treatment of suspected spinal cord compression.

3. Caution in chronic use: weight gain, osteoporosis, Cushing’s syndrome, proximal myopathy, psychosis, risk of GI bleeding, infection

4. Common drugs:

  • Prednisone

  • Dexamethasone (Decadron)

5. Skeletal muscle relaxants

  1. Mechanism: various.  GABA enhancing, central alpha-2 stimulation, etc.

  2. Advantage: useful adjuncts to analgesics for temporary relief of pain secondary to acute muscle injury

  3. Caution: dependence with chronic use, drowsiness

  4. Common drugs

  • Tizanidine (Zanaflex)

  • Baclofen: analgesic effect, independent of muscle relaxation

  • Flexeril

  • Soma: high addictive potential, limited use

6. Antihistamines

  1. Mechanism: anti-histamine effect

  2. Advantage: sleep aids and counteract itching from opioid

  3. Caution: weight gain with chronic use

  4. Common drugs

    • Hydroxyzine (Vistaril, Atarax)

    • Benadryl