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What is Neuropathic Pain and What is Causes of Neuropathic Pain and the Drugs for Managing Neurophathic Pain

Neuropathic Pain and Nociceptive Pain

Neuropathic pain is the result of an injury or problem with the nerves themselves. The pain is often triggered by an injury or an operation. Any event that can cause an injury to your body has the potential to damage the nerves at the same time.

For example, if a muscle is crushed, then the nerves within the muscle may also be crushed. Nerves can also be damaged or squeezed by tumours and scar tissue, or irritated by an infection.

Neuropathic pain often feels like burning, stabbing, or an electric shock. Strong pain from a light touch is also common. Neuropathic pain may last for months or years – long after the injury appears to have healed. Such pain means the problem is with the nervous system itself.

Examples: Failed Back Surgery Syndrome, Neuralgia, reflex sympathetic dystrophy (nerve damage), certain cancer pain, phantom limb pain, a trapped nerve, and peripheral neuropathy (widespread nerve damage).

Neuropathic Pain and Nociceptive Pain
Neuropathic Pain and Nociceptive Pain

There are many causes of peripheral neuropathy, diabetes being the most common. But it can also be caused by chronic alcohol abuse, exposure to toxins (unhealthy chemicals), lack of certain vitamins and a large variety of other problems. The cause is often never known.

Neuropathic pain is often described as a shooting or burning pain. It can go away on its own but is often chronic. Sometimes it is unrelenting and severe, and sometimes it comes and goes. It often is the result of nerve damage or a malfunctioning nervous system. The impact of nerve damage is a change in nerve function both at the site of the injury and areas around it.One example of neuropathic pain is called phantom limb syndrome. This rare condition occurs when an arm or a leg has been removed because of illness or injury, but the brain still gets pain messages from the nerves that originally carried impulses from the missing limb. These nerves now misfire and cause pain.Neuropathic pain can be distinguished from nociceptive pain by determining the quality of the pain. Typically, patients experience variations in sensation or hypersensitivity. Neuropathic pain symptoms can be classified as negative or positive. Negative symptoms of neuropathic pain are described as a loss of sensation or numbness. Positive symptoms are characterized by the increased perception of pain or abnormal sensations. Positive symptoms can be either induced by a stimulus or spontaneous (nonstimulus induced). Table 1 describes the types of symptoms.

Causes of Neuropathic Pain

Neuropathic pain often seems to have no obvious cause. But some common causes of neuropathic pain include:

  • Alcoholism
  • Amputation
  • Chemotherapy
  • Diabetes
  • Facial nerve problems
  • HIV infection or AIDS
  • Multiple myeloma
  • Multiple sclerosis
  • Nerve or spinal cord compression from herniated discs or from arthritis in the spine
  • Shingles
  • Spine surgery
  • Syphilis
  • Thyroid problems

What are the symptoms of neuropathic pain?

Symptoms of neuropathic pain
Symptoms of neuropathic pain

Many symptoms may be present in the case of neuropathic pain. These symptoms include:

  • Spontaneous pain (pain that comes without stimulation): Shooting, burning, stabbing, or electric shock-like pain; tingling, numbness, or a “pins and needles” feeling
  • Evoked pain: Pain brought on by normally non-painful stimuli such as cold, gentle brushing against the skin, pressure, etc. This is called allodynia. Evoked pain also may mean the increase of pain by normally painful stimuli such as pinpricks and heat. This type of pain is called hyperalgesia.
  • An unpleasant, abnormal sensation whether spontaneous or evoked (dysesthesia)
  • Trouble sleeping
  • Emotional problems due to disturbed sleep and pain
  • Pain that may be lessened in response to a normally painful stimulus (hypoalgesia)

Diagnosing Neuropathic Pain

To diagnose neuropathic pain, a doctor will conduct an interview and physical exam. He or she may ask questions about how you would describe your pain, when the pain occurs, or whether anything specific triggers the pain. The doctor will also ask about your risk factors for neuropathic pain and may also request both blood and nerve tests.

Your doctor will take a medical history and do a physical exam. Neuropathic pain is suggested by its typical symptoms when nerve injury is known or suspected. Your doctor will then try to find the underlying cause of the neuropathy and then trace the symptoms.

Neuropathic Pain Treatment

Anticonvulsant and antidepressant drugs are often the first line of treatment. Some neuropathic pain studies suggest the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as Aleve or Motrin, may ease pain. Some people may require a stronger painkiller. Be sure to discuss the pros and cons of the medicine you take with your doctor.

If another condition, such as diabetes, is involved, better management of that disorder may alleviate the pain. Effective management of the condition can also help prevent further nerve damage.

In cases that are difficult to treat, a pain specialist may use an invasive or implantable device to effectively manage the pain. Electrical stimulation of the nerves involved in neuropathic pain may significantly control the pain symptoms

Other kinds of treatments can also help with neuropathic pain. Some of these include:

  • Physical therapy
  • Working with a counselor
  • Relaxation therapy
  • Massage therapy
  • Acupuncture

Unfortunately, neuropathic pain often responds poorly to standard pain treatments and occasionally may get worse instead of better over time. For some people, it can lead to serious disability. A multidisciplinary approach that combines therapies, however, can be a very effective way to provide relief from neuropathic pain.

Pharmacologic Management

Various classes of medications have shown benefit for managing neuropathic pain. Medications for neuropathic pain are not likely to completely resolve pain; therefore, health care providers should discuss realistic goals with patients prior to initiating therapy. A reduction in pain of 30% is often considered a reasonable goal, along with potential improvements in sleep and depression, depending on the specific agent used. Patients should also be informed that many agents used for neuropathic pain often require a series of dose titrations and weeks of use to see a benefit. Classes of medications used for neuropathic pain include tricyclic antidepressants (TCAs), serotonin/ norepinephrine reuptake inhibitors (SNRIs), anticonvulsants, and, potentially, opioid therapy.3

Tricyclic Antidepressants
TCAs are often considered first-line for treatment of neuropathic pain and have shown benefit in clinical trials for diabetic peripheral neuropathy and postherpetic neuralgia.4 Benefits include low cost, as well as potential improvement in depression and/ or insomnia, which are frequently associated with neuropathic pain. Anticholinergic adverse effects (AEs), including dry mouth, constipation, and drowsiness, are possible with TCAs, although nortriptyline and desipramine are less likely than amitriptyline to cause AEs. Due to the risk of anticholinergic AEs, it is generally recommended to avoid the use of TCAs in the elderly. Use of TCAs should also be avoided in patients with a history of cardiac arrhythmias. TCAs should be initiated at a low dose, and the dose should be increased every 3 to 5 days until a target dose is reached or AEs become intolerable.

Serotonin/Norepinephrine Reuptake Inhibitors
SNRIs is a class of antidepressant medications that can be used to treat neuropathic pain. These medications include venlafaxine, duloxetine, and milnacipran. An advantage to SNRIs, similar to TCAs, is that they can help improve comorbid depression or anxiety. SNRIs should be used cautiously with other serotonergic medications due to the risk of serotonin syndrome. The most common AE associated with this class is nausea.

The anticonvulsants gabapentin and pregabalin are frequently used in the setting of neuropathic pain management. Gabapentin has been studied for managing various types of neuropathic pain, including diabetic neuropathy and postherpetic neuralgia, and gabapentin case study results have shown a benefit to its use over placebo in managing sciatica.5-7 Pregabalin has also been studied for managing postherpetic neuralgia and diabetic neuropathy, and the drug has shown efficacy in treating pain due to centrally mediated neuropathic pain and due to spinal cord injury.8-11

Along with TCAs, gabapentin is often considered a first-line agent for managing neuropathic pain. Use of pregabalin may be considered after failure with gabapentin due to a lack of efficacy or to intolerable AEs. Gabapentin and pregabalin are started at low doses and titrated every 3 to 7 days until a target dose is reached or AEs prevent further titrations. Both agents require dose adjustments in patients with renal impairment. Horizant (gabapentin enacarbil) and Gralise (gabapentin), extended-release gabapentin formulations, have been FDA-approved for management of postherpetic neuralgia and are designed to improve absorption of gabapentin; however, the cost of these medications is higher than an immediate-release gabapentin product.

Topiramate is another anticonvulsant that may be used for managing neuropathic pain; however, there is a lack of evidence to support the use of topiramate for managing neuropathic pain, and the study results are inconsistent.2 Therefore, topiramate is typically one of the last agents used to treat neuropathic pain. Other anticonvulsants, including carbamazepine, oxcarbazepine, lamotrigine, and lacosamide, have been studied for treating neuropathic pain and the results have been inconsistent, similar to those for topiramate.2

Lidocaine patches are an analgesic alternative for managing localized neuropathic pain. This patch is indicated for treating postherpetic neuralgia and allodynia. One to 3 patches can be used at the same time for up to 12 hours. Because lidocaine patches are associated with a low risk of AEs, they are an option for patients at risk of AEs due to oral therapies.

Due to the risk of serious AEs, including addiction, abuse, and overdose, opioids are generally considered a last-line option for managing neuropathic pain. If used in this setting, using the lowest possible dose is prudent (Online Table 2).

Drugs for Managing Neurophathic Pain

Drug Mechanism of Action Advantages Disadvantages Dosing Titration
Tricyclic Antidepressants Amitriptyline Increases serotonin and norepinephrine; blocks sodium channels Sedation; antidepressant effects; less anticholinergic (nortriptyline) Sedation; anticholinergic effects (amitriptyline); drug–drug interactions; cardiac arrhythmias Initial: 25 mg/day
Target: 100 mg/day
Increase by 25 mg intervals every 3-5 days
Nortriptyline Initial: 10 mg daily
Target: 100 mg/day
Increase in 10- mg intervals every 3-5 days
Serotonin/Norepinephrine Reuptake Inhibitors Venlafaxine Increases concentrations of serotonin and norepinephrine by inhibiting the reuptake of serotonin and norepinephrine into the synapse Antidepressant and antianxiolytic effects Nausea; changes in behavior/mood; hepatic impairment (venlafaxine and duloxetine); renal impairment (venlafaxine and milnacipran); blood pressure changes (venlafaxine and milnacipran) Initial: 37.5 mg/day
Target: 225 mg/day
Increase by 37.5 mg in the first week, then increase by 75 mg weekly
Duloxetine Initial: 30 mg/day
Target: 60 mg/day
Increase by 30 mg after first week
Milnacipran Initial: 12.5 mg/day
Target: 100 mg/day
Increase by 12.5 mg twice daily on days 2-3, and by 25 mg twice daily on days 4-7; then 50 mg twice daily
Calcium channel Alpha2-Delta Ligands Gabapentin Binds to alpha2-delta subunit of voltage-gated calcium channels and decreases pain mediators substance P, norepinephrine, and glutamate Inexpensive; sedation Sedation, weight gain, swelling, mental status changes, pharmacokinetic variability Initial: 300 mg/day
Target: 1800-2400 mg/day, divided in 3-4 daily doses
Increase by 300 mg every 3 days
Pregabalin Sedation; consistent pharmacokinetics Expensive; sedation; weight gain; swelling; mental status changes Initial: 150 mg/day, divided
Target: 600 mg/day, divided into 2-3 daily doses
Increase by 150 mg every 7 days
Sodium Channel Blocker
Topiramate Inhibits voltage-gated sodium channels and antagonizes glutamate receptors Promotes weight loss; migraine prophylaxis; typically well- tolerated Mental status changes (trouble with word recall; delayed response); kidney stones; sedation; glaucoma Initial: 25 mg/day
Target: 200 mg/day, divided into 2 daily doses
Increase by 25 mg every 7 days
Topical Analgesic Lidocaine patch Decreases permeability of neurons by sodium ions, which blocks conduction Minimal systemic absorption; localized anesthetic Redness; irritation; skin edema Apply 1-3 patches to painful area; on for 12 hr, then off for 12 hr No titration needed

Pharmacists can play a beneficial role in treating patients suffering from neuropathic pain, regardless of the area of specialty. Pharmacists know and understand the risks and benefits of these medications best, and can play an important role in educating patients and other health care providers. Pharmacists can ensure patients are well informed about the risks and can provide reasonable expectations regarding potential improvement in pain.

1 Comment

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