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Nociceptive Pain Medications
Nociceptive pain results from tissue damage. Injury to a specific area occurs, which causes intact neurons to report damage to the brain,
and pain is experienced. Nociceptive pain can be subdivided into somatic and visceral (gut) pain. Nociceptive pain can be a sharp sensation,
although other times it can be dull or aching. There may be radiation of the pain, especially visceral pain, but it will not be in a direct nerve
distribution. For example, gallbladder pain can radiate to the scapula. Nociceptive pain is generally responsive to and first treated with
nonsteroidal anti-inflammatory drugs (NSAIDs), followed with opioids for more severe or refractory pain. Conditions associated with
inflammation, bone pain, and joint disease are particularly responsive to NSAIDs. The following categories comprise the most commonly
used medications for nociceptive pain:
Acetaminophen (Tylenol)
Acetaminophen is an over-the-counter medication used to treat pain and fever. Acetaminophen works on the parts of the brain that receive
the “pain messages,” but it does not have the anti-inflammatory effects of the NSAIDs listed below. Often, however, in cases of chronic pain
there is no inflammation at the site of the pain, and thus Tylenol may be an appropriate treatment choice. Tylenol is a safe medication when
used appropriately, but can be very dangerous when used inappropriately. The risk of liver or kidney damage is significant when more than
the recommended dose of Tylenol is used. If you have known liver disease, acetaminophen should only be consumed under your doctor’s
supervision. Acetaminophen is often combined with other pain medications to cause an additive effect.
NSAIDs
These are the nonsteroidal anti-inflammatory drugs (NSAIDs) and many are available over-the-counter without a prescription. Included in
this category are aspirin (Bayer), ibuprofen (Advil, Motrin), ketoprofen (Orudis KT), and naproxen sodium (Aleve). These medications relieve
pain by reducing the production of prostaglandins, which are hormone-like substances that causes pain and inflammation. Therefore,
NSAIDs can be extremely effective at reducing inflammation and calming swelling and irritation. NSAIDs are most beneficial in cases of
acute pain, or flare-ups in patients with chronic pain. In general these should not be used on a daily basis for the treatment of chronic pain.
When used on a daily basis for a period of several years, there is a risk of damage to the kidneys that can be significant. Furthermore, there
is a well-known risk of gastric ulcer formation with NSAIDs. While the newer, COX-2 inhibitors (Celebrex, Vioxx), were designed to avoid this
complication, caution should still be used if there is a risk of ulcers or GI bleeding.
COX2 Inhibitors
Recently, a new class of NSAIDs has become available, the COX2 inhibitors. Currently available in this class is celecoxib (Celebrex).
Selective blockade of cyclooxygenase permits analgesia and an anti-inflammatory effect while minimizing the risk of GI toxicity and bleeding.
The COX2 inhibitors have been shown to be equally effective as other NSAIDS, but do not show evidence of greater analgesia. The COX2
inhibitors are considerably more expensive than other over-the-counter NSAIDS. However, if an NSAID is truly needed and there is concern of
GI bleeding, the total cost may be lowered by using one of these agents rather than adding a relatively expensive prophylactic drug such as
misoprostol or a pump-inhibitor to counteract the side effects of NSAIDs. Other COX-2 inhibitors including rofecoxib (Vioxx) and valdecoxib
(Bextra) were withdrawn from the market due to potential cardiovascular side effects.
Opioids
When treating chronic pain, narcotic opioids should be considered if pain cannot be otherwise controlled. Although these medications can
be dangerous and addicting, they can also be effective when used appropriately.
An opioid is a chemical substance that has a morphine-like action in the body. The term opioid is derived from opium, which is an extract
from the poppy plant. These agents have been available for centuries to relieve pain. Opioids work by binding to opioid receptors, which are
found principally in the central nervous system and the gastrointestinal tract. The receptors in these two organ systems mediate both the
beneficial effects, and the undesirable side effects. All of the opioids have similar clinical effects that vary from one another in potency, speed
on onset, and duration of action. Both short-acting and long-acting formulations are available, as some opioids are used around-the-clock
while others are used as needed for breakthrough pain.
One common mistake when treating chronic pain with opioid medications is using the short acting types of medication (e.g. Percocet,
Morphine, Vicodin, etc.). While these medications are useful for acute pain, they are also associated with sedating and euphoric side effects.
The short acting nature of these medications encourages overuse and the development of tolerance. Long-acting opioids may have fewer
cognitive side effects and better control of chronic pain. Although no adequate long-term studies have shown their effectiveness in the
treatment of chronic nonmalignant pain, and they are not approved for this use, they are often used for this type of pain management. Side
effects may include GI upset, nausea, disturbed sleep, constipation, and addiction. Studies show about 5-15% of chronic pain patients using
narcotic pain medications develop dependence.
The following is a comprehensive listing of the broad classes of narcotics:
- Natural Opioids: alkaloids contained in the resin of the opium poppy (morphine, codeine, thebaine, and oripavine).
- Semi-synthetic Opioids: from the natural opioids (hydromorphone, hydrocodone, oxycodone, and heroin).
- Fully-synthetic Opioids: (fentanyl, pethidine, methadone, and propoxyphene).
- Endogenous Opioid Peptides: produced naturally in the body (endorphins, enkephalins, dynorphins, and endomorphins).
Atypical Opioids
Tramadol (Ultram) is an atypical opioid that is a centrally acting analgesic, used for treating moderate to severe pain. It is a synthetic agent
and analogue of codeine, and appears to have actions on the GABAergic, noradrenergic and serotonergic systems. Unlike most other
opioids, Tramadol is not considered a controlled substance in many countries (including the U.S). An extended-release formula is available
to treat moderate to severe chronic pain when treatment is needed around the clock.
The Opioid Controversy
Considerable debate exists about the use of opioids for treatment of chronic pain of non-cancer origin. Many physicians feel that opioids
can play an important role in the treatment of all types of chronic pain, including non-cancer pain. Others caution against the widespread use
of opioids noting problems with tolerance, loss of benefit with time, and escalating usage with decreasing function in many individuals. The
use of opioids (or for that matter any treatment) makes sense when the benefits outweigh the risks and negative side effects. Benefit is
suggested when there is a significant increase in the person’s level of functioning, when there is a reduction or elimination of pain
complaints, when there is a more positive hopeful attitude and when side effects are minimal or controllable. The dilemma with the long term
use of opioids is that while there is a role for opioids in chronic, non-cancer pain, it is well known that prolonged use of opioids may result in
problems including tolerance, hyperalgesia (abnormal pain sensitivity), hormonal effects (decreased testosterone levels, decreased libido
and sex drive, irregular menses), depression, and suppression of the immune system. While opioid treatment may be prescribed to reduce
pain and improve function, the treatment may actually result at times in just the opposite.
Neuropathic Medications
Neuropathic pain is associated with injury to the nerve. Often this type of pain is characterized by burning sensations, increased sensitivity
or shooting sensations over the affected area. Patients often describe this type of pain as severe, sharp, lancinating, lightening-like, stabbing,
burning, numbness, tingling, and/or weakness. It is important to understand neuropathic pain because it has very different treatment options
from other types of pain. Remedies for nociceptive pain, such as NSAIDs and opioids, do not work as well for neuropathic pain, which is only
marginally affected by opioids and anti-inflammatories. Neuropathic pain seems to respond best to membrane-stabilizing medications.
These medications are made up of the anti-convulsants, tricyclic anti-depressants, and select anti-depressant medications. These
medications act by blocking the brain's neurotransmitters. The antidepressant medications also have beneficial effects of improved mood,
decreased anxiety, and improved sleep cycle. These medications are not addictive, and when appropriately managed have few side effects.
Anticonvulsants
The anticonvulsant medications can be divided into first or second-generation agents. The second-generation medications are generally
better tolerated and have fewer central nervous system (CNS) side effects than the first generation agents. Of the first generation agents,
carbamazepine (Tegretol) has been effective in the treatment of Trigeminal neuralgia. Evidence has also shown moderate efficacy in the
treatment of postherpetic neuralgia and diabetic neuropathy. Carbamazepine’s main side effect is sedation. Patients treated with it should
also have complete blood counts (CBCs) and liver function tests (LFTs) monitored, as blood dyscrasias and liver abnormalities can occur
with the medication. These generally resolve with discontinuation of the drug.
The second-generation antiepileptic agents have shown the best documented resolution of neuropathic pain, although the mechanism of
action of these drugs remains unknown. Gabapentin (Neurontin) is the first line agent in the treatment of painful diabetic neuropathy and
postherpetic neuralgia. Many physicians begin treatment with this agent, mostly because it has been well tolerated, even at high doses. In
fact, some evidence shows an anti-anxiolytic effect, and therefore may be helpful for anxious patients. Unlike carbamazepine, it lacks
significant interactions with other drugs. Patients may experience nausea, especially with rapidly increasing doses, or dizziness with higher
doses.
The FDA recently approved the use of the new anticonvulsant drug, pregabalin (Lyrica), for the treatment of neuropathic pain. It was
designed as a more potent successor to gabapentin. Lyrica is also been shown to be effective in the treatment of diabetic neuropathy and
postherpetic neuralgia. This drug can be given less frequently than gabapentin (twice daily versus three times daily), although it is a
Schedule V controlled substance. The FDA also recently approved the use of Lyrica for the treatment of Fibromyalgia, and it is currently the
only FDA-approved drug for the treatment of pain associated with Fibromyalgia.
Antidepressants
Chronic pain often is associated with emotional havoc, which interferes with the improvement of pain. Antidepressant medications have
been show to have success with the treatment of chronic pain. In addition, these medications have the added benefit of improved mood,
improved sleep cycles and decreased anxiety. Antidepressants are drugs that can treat pain and/or emotional conditions by adjusting levels
of neurotransmitters (natural chemicals) in the brain. They can increase the availability of the body's signals for well-being and relaxation,
enabling pain control for people with chronic pain conditions that do not completely respond to the usual treatments.
Although several categories of antidepressants exist, the tricyclic antidepressants are most commonly used for the treatment of chronic
pain. In low doses, these medicines are effective at relieving pain, while higher doses have a more typical antidepressant effect. Amitriptyline
(Elavil) is the antidepressant most commonly prescribed from this group, simply because it has been studied the most thoroughly. Other
tricyclic antidepressants used for pain control include: Imipramine (Tofranil), Nortriptyline (Pamelor) and Desipramine (Norpramin). Tricyclic
antidepressants seem to work best for the burning or searing pain common after nerve damage, which sometimes occurs with diabetes,
shingles or strokes. These drugs are also effective in some people for Fibromyalgia, or as a preventative for migraines. Tricyclic
antidepressants don't cause dependence or addiction, and they're safe to take for long periods of time. But they can make you drowsy. In
addition, these drugs may cause dry mouth, constipation, weight gain, difficulty with urination and changes in blood pressure. To reduce or
prevent side effects, your doctor will likely start you at a low dose and slowly increase the amount. Most people are able to take tricyclic
antidepressants, particularly in low doses, with only mild side effects. The doses that are effective for pain are typically lower than the doses
used for depression.
Two newer forms of antidepressants — selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake
inhibitors (SNRIs) — have fewer side effects than tricyclic antidepressants and are sometimes used to treat chronic pain. SSRIs include
such drugs as paroxetine (Paxil) and fluoxetine (Prozac). People who have chronic pain may feel better while taking SSRIs, but this effect is
believed to result more from the easing of accompanying depressive symptoms rather than from actual pain relief. Drugs such as
venlafaxine (Effexor) and duloxetine (Cymbalta) are SNRIs, which appear to be more effective than SSRIs at pain control, particularly
neuropathic pain caused by damaged nerves. Cymbalta has an FDA indication for treating diabetic peripheral neuropathy. SSRIs and SNRIs
are known to have fewer side effects than the tricyclic antidepressants, and therefore, may be better treatment options for chronic neuropathic
pain.
Conclusion
This is an introduction to the medication management of chronic nonmalignant pain. One of the most useful ways to conquer pain is to
understand it, and hopefully this will merely be the first of many resources you turn to. Furthermore, there are many treatment modalities
besides medications which may be very helpful for your chronic pain management.
References
Ballantyne JC (2006). "Opioids for chronic non-terminal pain". South. Med. J. 99 (11): 1245-55. PMID 17195420
Fields HL, Martin JB (2005). Pain: Pathophysiology and management. In DL Kasper et al., eds., Harrison's Principles of Internal Medicine,
16th ed., vol. 1, pp. 71–76. New York: McGraw-Hill
Katz, WA "The Needs of a Patient in Pain" Amer. J. Med. 1998. 105(1B) Pages 2S-7S.
Marcus, DA "Treatment of Nonmalignant Chronic Pain" Amer. Family Physician. 2000. 61(5) Pages 1331-8.
Munir MA, Enany N, Zhang JM. "Non-opioid analgesics". Med. Clin. North Am. 2007. 91 (1): 97-111. PMID 17164106.
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Medication Management for Chronic Pain
by Nicole Berardoni M.D, Tory McJunkin M.D, and Paul Lynch M.D
Pain is a universal phenomenon, experienced at some time in everyone’s life. It
interferes with enjoyment, interrupts work, recreation, and relationships. Though it is
universal, pain is so complex and subjective that it is difficult to comprehend and treat.
When a patient has a chronic pain condition, several pharmacologic treatment
modalities exist to address the pain. In choosing a medication for pain control,
physicians must first correctly diagnose the type of pain a patient is experiencing.
Chronic pain may be the result of inflammation or injury to somatic or visceral tissue,
termed nociceptive pain. Chronic pain may also be the result of injury or damage to the
nerve itself, termed neuropathic pain. Nociceptive pain is most commonly treated with
anti-inflammatory and analgesic medications, such as nonsteroidal anti-inflammatory
drugs (NSAIDS) and opioids. Neuropathic pain, however, is treated differently using
medications that act on neurotransmitters and excitable nerves (e.g., antidepressants,
anticonvulsant agents).
The following categories contain the most commonly prescribed and most well-
documented agents for the treatment of both nociceptive and neuropathic chronic pain.
by Nicole Berardoni M.D, Tory McJunkin M.D, and Paul Lynch M.D
Pain is a universal phenomenon, experienced at some time in everyone’s life. It
interferes with enjoyment, interrupts work, recreation, and relationships. Though it is
universal, pain is so complex and subjective that it is difficult to comprehend and treat.
When a patient has a chronic pain condition, several pharmacologic treatment
modalities exist to address the pain. In choosing a medication for pain control,
physicians must first correctly diagnose the type of pain a patient is experiencing.
Chronic pain may be the result of inflammation or injury to somatic or visceral tissue,
termed nociceptive pain. Chronic pain may also be the result of injury or damage to the
nerve itself, termed neuropathic pain. Nociceptive pain is most commonly treated with
anti-inflammatory and analgesic medications, such as nonsteroidal anti-inflammatory
drugs (NSAIDS) and opioids. Neuropathic pain, however, is treated differently using
medications that act on neurotransmitters and excitable nerves (e.g., antidepressants,
anticonvulsant agents).
The following categories contain the most commonly prescribed and most well-
documented agents for the treatment of both nociceptive and neuropathic chronic pain.
Book I - Pain Syndromes
Chapter 1 Low Back Pain
Chapter 2 Neck Pain
Chapter 3 Cancer Pain
Chapter 4 Headaches
Chapter 5 Spinal Stenosis
Chapter 6 Sciatica
Chapter 7 Arthritis
Chapter 8 Fibromyalgia
Chapter 9 Motor Vehicle Injuries
Chapter 10 Complex Regional Pain
Syndrome
Chapter 11 Vertebral Body
Fractures
Chapter 12 Hip and Leg Pain
Chapter 13 Diabetic Peripheral
Neuropathy
Book II - Interventional Procedures
Chapter 14 Epidural Steroid
Injection
Chapter 15 Facet Injections/Medial
Branch Blocks
Chapter 16 Radiofrequency Ablation
Chapter 17 Spinal Cord Stimulator
Implants
Chapter 18 IntraDiscal
Electrothermal Therapy (IDET)
Chapter 19
Vertebroplasty/Kyphoplasty
Chapter 20 Discography
Chapter 21 Percutaneous
Discectomy
Chapter 22 Occipital Nerve Block
Chapter 23 Sympathetic Block
Chapter 24 Stellate Ganglion Block
Chapter 25 Intrathecal Pump
Implants
Chapter 26 Caudal Steroid Injection
Chapter 27 Adhesiolysis
Chapter 28 Cervical Steroid
Injection
Chapter 29 Sacroiliac Joint
Injections
Chapter 30 Celiac Plexus Block
Chapter 31 Head and Neck
Procedures
Chapter 32 Joint Injections
Chapter 33 Continuous Catheter
Nerve Blocks
Chapter 34 Peripheral Nerve
Stimulation/Field Stimulation
Chapter 35 Disc Denervation
Book III Other Treatments
Chapter 36 Medication Management
Chapter 37 Acupuncture
Chapter 38 Prolotherapy
Chapter 39 Botox
Chapter 40 Massage
Chapter 41 Alternative and
Complementary Medicines
Chapter 42 Exercise and Nutrition
Counseling
Chapter 43 Prayer
Chapter 44 Cognitive Behavioral
Therapy
Chapter 45 Group Therapy
Chapter 46 Biofeedback
Chapter 47 Chiropractic
Manipulations
Chapter 48 Vitamin Supplements
Chapter 49 Customized
Pharmaceutical Formulations
Chapter 50 Hormone Therapy
Frequently Asked Questions
Chapter 1 Low Back Pain
Chapter 2 Neck Pain
Chapter 3 Cancer Pain
Chapter 4 Headaches
Chapter 5 Spinal Stenosis
Chapter 6 Sciatica
Chapter 7 Arthritis
Chapter 8 Fibromyalgia
Chapter 9 Motor Vehicle Injuries
Chapter 10 Complex Regional Pain
Syndrome
Chapter 11 Vertebral Body
Fractures
Chapter 12 Hip and Leg Pain
Chapter 13 Diabetic Peripheral
Neuropathy
Book II - Interventional Procedures
Chapter 14 Epidural Steroid
Injection
Chapter 15 Facet Injections/Medial
Branch Blocks
Chapter 16 Radiofrequency Ablation
Chapter 17 Spinal Cord Stimulator
Implants
Chapter 18 IntraDiscal
Electrothermal Therapy (IDET)
Chapter 19
Vertebroplasty/Kyphoplasty
Chapter 20 Discography
Chapter 21 Percutaneous
Discectomy
Chapter 22 Occipital Nerve Block
Chapter 23 Sympathetic Block
Chapter 24 Stellate Ganglion Block
Chapter 25 Intrathecal Pump
Implants
Chapter 26 Caudal Steroid Injection
Chapter 27 Adhesiolysis
Chapter 28 Cervical Steroid
Injection
Chapter 29 Sacroiliac Joint
Injections
Chapter 30 Celiac Plexus Block
Chapter 31 Head and Neck
Procedures
Chapter 32 Joint Injections
Chapter 33 Continuous Catheter
Nerve Blocks
Chapter 34 Peripheral Nerve
Stimulation/Field Stimulation
Chapter 35 Disc Denervation
Book III Other Treatments
Chapter 36 Medication Management
Chapter 37 Acupuncture
Chapter 38 Prolotherapy
Chapter 39 Botox
Chapter 40 Massage
Chapter 41 Alternative and
Complementary Medicines
Chapter 42 Exercise and Nutrition
Counseling
Chapter 43 Prayer
Chapter 44 Cognitive Behavioral
Therapy
Chapter 45 Group Therapy
Chapter 46 Biofeedback
Chapter 47 Chiropractic
Manipulations
Chapter 48 Vitamin Supplements
Chapter 49 Customized
Pharmaceutical Formulations
Chapter 50 Hormone Therapy
Frequently Asked Questions