Download 2. CHRONIC PAIN

Pain management
Chronic pain
2. CHRONIC PAIN
• Pain persisting for > 6 months to years
• Chronic pain can be episodic or continuous, or
combination of both
• Chronic pain can cause deteriorating QoL ,changes in appetite,
psychomotor retardation, irritability, social withdrawal, sleep
disturbances, & depression and decreased wll being
2. CHRONIC PAIN (cont’d)
• Can be nociceptive, neuropathic/ functional, or
both
• Subtypes include:
1. pain that persists beyond normal healing time
for acute injury (e.g., complex regional pain
syndrome)
2. pain related to chronic disease (e.g., pain
secondary to osteoarthritis)
3. pain without identifiable organic cause
(e.g., fibromyalgia)
4. pain associated with cancer
• Neuropathic pain, resulting from damage to or pathology within the
nervous system, can be central (like stroke)or peripheral(like DM).
Causes of neuropathic pain are multiple, and include diabetes
mellitus, postherpetic neuralgia, and stroke.
• Nociceptive pain, in contrast, is caused by stimuli that threaten or
provoke actual tissue damage(activation of nociceptors)
• . Nociceptive pain is often due to musculoskeletal conditions,
inflammation, or mechanical/compressive problems. (eg. Low back
pain)
• APPROACH TO THE PATIENT
Treatment options for chronic pain generally fall into six major
categories:
1. pharmacologic.
2. physical medicine.
3. behavioral medicine.
4. Neuromodulation.
5. interventional.
6. surgical approaches.
• PHARMACOLOGIC OPTIONs
• NSAID and APAP
• Tramadol
• Opioids
• Alpha 2 adrenergic agonists
• Antidepressants (tricyclics and [SNRIs])
• Antiepileptic drugs (gabapentin, pregabalin, and other
anticonvulsants)
• Muscle relaxants
• N-methyl-d-aspartate (NMDA) receptor antagonists
• Topical analgesic agents
• For most patients, the initial treatment of neuropathic pain involves either
antidepressants (TCA or SNRI) or calcium channel alpha 2-delta ligands
(gabapentin and pregabalin), with adjunctive topical therapy (eg, topical
lidocaine) when pain is localized .
• opioids should be considered a second-line option. They may be considered
earlier in the treatment of select patients, such as those with severe intractable
pain, episodic exacerbations of severe pain, or neuropathic cancer pain.
• Combination therapy is often required, because less than half of patients with
neuropathic pain will respond to a single agent .
• The role of opioid therapy in the more severe forms of acute pain and in cancer
pain is well established, but opioid administration in chronic noncancer pain
remains controversial.
• When pharmacotherapy for nociceptive pain is required,
acetaminophen is typically recommended as a first-line therapy for
pain related to osteoarthritis and chronic low back pain . However,
acetaminophen is less effective than nonsteroidal anti-inflammatory
drugs (NSAIDs) and has the potential for hepatic toxicity at doses of
>4 g per day .
• An alternative first line agent is an oral NSAID, which is effective for
mild-to-moderate chronic low back pain or osteoarthritis .
• Opioid medications should be used on a chronic basis only in patients
who are assessed to be at low risk for substance abuse, and who have
persistent pain despite trials of nonopioid analgesics and
antidepressants.
Risk factors:
• Chronic kidney disease, advanced age - avoid NSAIDs and COX-2 inhibitors.
• Peptic ulcer disease, glucocorticoid use - avoid NSAIDs.
• Hepatic disease - avoid NSAIDs, COX-2 inhibitors, and acetaminophen (APAP);
use TCAs or duloxetine first line.
• Cardiovascular disease or risk - use lowest effective dose of NSAIDs ; in patients who
require treatment, suggest naproxen.
• ANTIDEPRESSANTS
• Both (TCAs) and (SNRIs) possess analgesic qualities while the
evidence for the effectiveness of (SSRIs) is weaker.
• Analgesic antidepressants may provide pain relief separate from their
antidepressant effects, since analgesic effects appear to occur earlier
(eg, after approximately a week) and at lower doses than for
antidepressant effects.
• Tricyclic antidepressants
• Amitriptyline has been the most widely studied TCA in chronic pain ,
although a number of others, including doxepin, imipramine,
nortriptyline, and desipramine also have been used with success.
TCAs are believed to have independent analgesic effects as well as an
ability to relieve the depressive symptoms associated with chronic
pain.
• TCAs prescribed for chronic pain have typically been given at lower
doses than those used in depression, although higher doses have
provided superior analgesia in some studies. Some patients respond
only as the dose is steadily increased.
• TCAs (eg, nortriptyline) may be started at 10 mg/day and slowly
titrated up to an effective analgesic dose (eg, 75 mg/day).
• It can take up to six to eight weeks, including two weeks at the
highest dose tolerated, for an adequate trial of treatment with TCA,
although the onset of analgesia may be after one week and typically
occurs at lower doses than needed for the treatment of depression .
• Adverse effects include:
1. anticholinergic effects,
2. antihistaminergic effects (doxepin has the most potent
antihistaminergic effects),
3. alpha-1 adrenergic receptor blockade,
4. and cardiac effects (increasing intraventricular conduction,
prolonged QT interval, prolonged conduction through the
atrioventricular node).
• amitriptyline has the most potent anticholinergic effects and
desipramine has the least, and thus is the least sedating.
• Anticholinergic adverse effects including dry mouth, orthostatic
hypotension, constipation, and urinary retention can be reduced by
starting with low doses administered at bedtime and with slow
titration to higher dose, as well as by using a secondary amine TCAs
(eg, nortriptyline or desipramine).
• Stool softeners can be used if there is a tendency toward
constipation.
• Patients should understand that although analgesia may occur in
days, it frequently will take weeks to obtain any significant benefit.
• It is important for patients to know that many of the unpleasant side
effects, such as dry mouth, mental clouding, and others, may diminish
in days to weeks.
• Doses should be increased gradually to the point of effect or
intolerable side effects.
• When one antidepressant does not work, another can be tried.
Sometimes decreasing the dose or substituting a different member of
this class, one with fewer anticholinergic effects, will make the
difference.
• TCAs relatively contraindicated in patients with severe cardiac
disease, particularly conduction disturbances; obtaining a
pretreatment ECG is recommended.
• They should also be avoided in patients with severe gastrointestinal
dysfunction since such symptoms may be exacerbated.
• Desipramine and nortriptyline can be used safely in older patients;
their starting dose should be reduced by one-half, and patients
should be watched carefully for untoward effects as the doses are
escalated slowly.
• Serotonin norepinephrine reuptake inhibitors
• Four (SNRIs) are available in the United States: venlafaxine,
desvenlafaxine, duloxetine, and milnacipran.
• Duloxetine and venlafaxine have been studied in peripheral
neuropathic pain while milnacipran has been studied only in
fibromyalgia.
• Venlafaxine — is used for peripheral neuropathic pain and may be
used to treat diabetic neuropathy.
• venlafaxine should be prescribed with caution in patients with cardiac
disease because of Cardiac conduction abnormalities in a some
patients, and blood pressure increases can occur
• In addition, venlafaxine should be tapered when treatment is being
discontinued because of withdrawal symptoms.
• Duloxetine
• Duloxetine hydrochloride is effective in the treatment of painful
diabetic neuropathy, fibromyalgia, and more recently chronic low
back pain and osteoarthritis , as well as major depression, anxiety,
and stress urinary incontinence.
• The most common side effects : include nausea, dry mouth, insomnia,
drowsiness, constipation, fatigue, and dizziness.
• Side effects are reduced by administering duloxetine 30 mg once daily
for one week before increasing to 60 mg once daily.
• Duloxetine should be avoided in patients with hepatic or severe renal
insufficiency. Gradual tapering is recommended at discontinuation to
avoid withdrawal symptoms.
• ANTICONVULSANTS
• Three antiepileptic drugs (gabapentin, pregabalin, and carbamazepine)
are among the five drugs approved by (FDA) for the treatment of
neuropathic pain .
• Gabapentin and pregabalin bind to the voltage-gated calcium channels at
the alpha 2-delta subunit and inhibit neurotransmitter release.
• Gabapentin is found effective for the treatment of postherpetic neuralgia
and painful diabetic neuropathy .
• Treatment with gabapentin should be initiated at a low dose with gradual
increases until pain relief, dose limiting adverse effects, or 3600 mg per day
in three divided doses is achieved.
• An adequate trial of treatment with gabapentin can require two months or
more.
• Pregabalin was designed as a lipophilic (GABA) analog to facilitate diffusion
across the blood-brain barrier .
• Pregabalin may provide analgesia more quickly than gabapentin
• The most common side effects of gabapentin & pregabalin include
dizziness, somnolence, peripheral edema, & dry mouth
• Although gabapentin and pregabalin have few drug interactions, both can
produce dose-dependent dizziness and sedation that can be reduced by
starting with lower doses and titrating cautiously.
• Pregabalin has been reported to cause euphoria, and is classified as a
Schedule V controlled substance in the United States.
• Other antiepileptics
• including topiramate, lamotrigine, levetiracetam ,phenytoin, sodium
valproate, zonisamide, tiagabine, and the benzodiazepine clonazepam
• in general these agents should be reserved for second-line treatment
in patients who don't respond to or cannot tolerate other
medications.
• A 2007 systematic review of lamotrigine for acute and chronic pain
concluded that it does not have a place in the treatment of pain,
given other more effective therapies .
• A 2014 systematic review of levetiracetam found no evidence to
support the use of levetiracetam in neuropathic pain .
• One exception is the use of carbamazepine or its derivative
oxcarbazepine as specific first-line therapy in the management of
trigeminal neuralgia
• ADJUVANT MEDICATIONS The usefulness of pairing adjuvant agents
with pain medications is well known to pain management specialists.
Some adjuvants are used to treat the side effects associated with pain
medications, while others potentiate analgesia.
1. Topical agents :
• Topical agents for the management of pain have several potential
advantages over systemic drugs: delivery at the site of insult, lower
initial rates of systemic absorption, fewer systemic effects, and
patient preference. Patients often perceive topical preparations to be
safer than their oral equivalents. However, significant systemic
concentration can be achieved by topical application and systemic
side effects are possible.
• Topical lidocaine (local anesthetic)
Topical lidocaine is most appropriate for patients with well localized neuropathic pain. Although it can be used as
monotherapy, it is often used as an adjunct to systemic medication.
• Capsaicin cream
is an alkaloid derived from chili peppers; repeated application is thought to deplete substance P from primary
afferent neurons . Capsaicin is available as a cream and as patches. A systematic review found that capsaicin had
moderate to poor efficacy for relief of chronic musculoskeletal or neuropathic pain, but might be useful as an
adjunctive therapy or for patients unresponsive to other treatments . Capsaicin has been used in patients with post
herpetic neuralgia, HIV neuropathy, and diabetic neuropathy.
Capsaicin cream must be applied three to four times per day over the entire painful area for up to six to eight
weeks before optimal pain relief can be achieved, while the patch, administered under close clinician supervision,
is applied as a single 60-minute application. The major adverse effects of capsaicin are burning, stinging, and
erythema at the site of application, leading to intolerance in up to one-third of patients.
• Topical nonsteroidal anti-inflammatory drugs
• Topical nonsteroidal anti-inflammatory drugs, in the form of a gel, spray, or cream, provide modest relief for
acute musculoskeletal pain . Evidence of effectiveness for these agents for chronic low back pain, widespread
musculoskeletal pain, and peripheral neuropathic pain, however, is weaker than for acute pain . A systematic
review of four randomized trials found that a topical 1.5 percent solution of diclofenac was more effective than a
control vehicle in the relief of knee osteoarthritic pain, and was generally well tolerated . A systematic review
found that response rates for topical salicylates for chronic pain are lower than for topical nonsteroidals .
• Topical doxepin
• Topical doxepin, available in topical formulation for the treatment of pruritus, had only minimal effect on pain
reduction in one small trial .
2. Antispasmodics A wide variety of pain conditions, both acute and
chronic, may be accompanied by painful muscle spasm.
Antispasmodics can be useful in treating this aspect of the patient's
symptoms, but their action may be more the result of sedation
rather than muscle relaxation.
• These medications may also cause CNS depression and should be
used cautiously when combined with other CNS depressant
medications.
• Two examples: tizanidine and baclofen
• Botulinum toxin — Botulinum toxin type A (BTX-A), a potent neurotoxin,
may be effective in reducing the dose of opioids needed for analgesia in
patients with severe post herpetic neuralgia. but further study in larger
trials is needed for its role in both neuropathic and nociceptive chronic
pain
• Benzodiazepines — Benzodiazepines may be utilized in patients who
would benefit from anxiolysis. These are selectively employed in cancer
patients and in noncancer pain complicated by anxiety disorder.
• The disadvantage of this class of drugs relates to their addictive potential,
as well as their potentiation of sedative effects and respiratory depression
in patients who use opioids concurrently. In a study of 1220 patients with
noncancer pain on long-term opioids, concurrent benzodiazepine use was
associated with greater pain severity, prescription of higher doses of
opioids, substance use, and greater mental health comorbidities.
• OPIOIDS — The role of opioid therapy in the more severe forms of acute
pain and in cancer pain is well established, but opioid administration in
chronic noncancer pain remains controversial.
• Chronic pain is best accomplished by around-the-clock (ATC)
administration schedules that inhibit serum analgesic concentrations
from falling below the point at which a patient experiences suffering
of pain
• As-needed schedules are to be used in conjunction with ATC regimens &
are used when patients experience breakthrough pain
• In chronic opiate dependence, opioid dose can be reduced every 3-5 days
without inducing withdrawal symptoms
• Methadone has a long plasma half-life and accumulates with continuous
dosing, and therefore it should be used with caution in the elderly. It is
more often used for the treatment of chronic pain
Central Analgesics
• Tramadol has two modes of action: μ-opiate receptor
binding & inhibition of norepinephrine & serotonin
reuptake
• It is indicated for relief of moderate to moderately severe
pain
• Has side-effect profile similar to that of opioid analgesics
(e.g., dizziness, euphoria, hallucinations, cognitive
dysfunction, & constipation)
• May have place in treating patients with chronic pain,
especially neuropathic pain
• NONPHARMACOLOGIC THERAPIES
• physical interventions (including physical therapy, acupuncture,
chiropractic manipulation, massage, and others) and the
psychoeducational interventions such as cognitive-behavioral therapy,
family therapy, psychotherapy, and patient education.
• Behavioral medicine approaches
• Cognitive behavioral therapy
• Biofeedback
• Relaxation therapy
• Psychotherapy and individual or group counseling
• Aerobic exercise
• Acupuncture
• Physical and occupational therapy
• Chiropractics and osteopathic manipulation
• Ultrasonic stimulation
• Electrical neuromodulation
• Transcutaneous electrical nerve stimulation (TENS)
• Spinal cord stimulation
• Thermal applications (heat/cold)
• Interventional approaches
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Ablative techniques
Botulinum toxin injections
Nerve blocks
Trigger point injections
Epidural steroid injections
• Surgical approaches
• Minimally invasive techniques