Neuropathic Pain: Primary Care Update

An estimated 6.9% to 10% of the population is believed to suffer from neuropathic pain,¹ the result of damage to nerves, the spinal cord, or the brain.

A wide variety of painful conditions fall under the heading of neuropathic pain including central pain conditions, where there is damage to the central nervous system, such as post-stroke pain and pain secondary to Parkinson's Disease; conditions where the pain appears to result from both some form of peripheral injury and a central nervous system response to this, eg, complex regional pain syndrome; and those where the damage is believed to be in peripheral nerves.

In the category of neuropathic pain caused by damage to peripheral nerves are the two most common forms: postherpetic neuralgia and diabetic peripheral neuropathic pain. This primary care update will focus on these although for the most part the treatment approaches that are effective for the these conditions are also appropriate for most of the other forms of neuropathic pain.

Postherpetic Neuralgia (PHN)

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With the development of a varicella vaccine, the risk of contracting the virus has been greatly reduced. For those who have had chickenpox, vaccination can help prevent PHN.

The bad news is that many people in the age group most at risk for PHN (age ≥ 50 years) still haven't received the vaccine; also, the vaccine does not provide 100% immunity and the protection it does provide appears to decrease over time, leaving even those who receive it vulnerable to PHN.

PHN primarily affects those over age 50. In the US, PHN develops in approximately 18% of people age 50 or older and in 33% of those 80 or older.² Diagnosis is typically straightforward as the pain is usually preceded by the herpes zoster rash along the distribution of a single nerve root and the pain follows the same distribution. By far the most common site of PHN is the thoracic region (Figure, above) followed by the face, along the distribution of the trigeminal nerve (Figure, below).

[[{"type":"media","view_mode":"media_crop","fid":"55265","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_3363242677201","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6910","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 250px; float: right; width: 176px;","title":" ","typeof":"foaf:Image"}}]]Pain from PHN is usually described as burning or lancinating. Allodynia over the affected area also is common-where stimulation that does not usually cause pain becomes painful. Even clothing rubbing lightly against the affected area can be painful. Allodynia is an uncommon symptom in most pain disorders and is typically only seen in one other neuropathic condition, complex regional pain syndrome (see box for discussion of this disorder).

If the patient seeks medical treatment for the herpes zoster rash within 72 hours after it develops, an antiviral medication (acyclovir, famcilovir, valacyclovir) may limit the severity.

Once the pain begins, an OTC analgesic (eg, acetaminophen or NSAID) may be sufficient. However, many patients require prescription analgesics to attain relief.

Next: PHN Treatment>>

PHN Treatment

The most effective medications for most forms of neuropathic pain including PHN are the tricyclic antidepressants (TCAs); the other serotonin-norephinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine; and, the anticonvulsants gabapentin and pregabalin.³ Unfortunately there are still no known factors that predict which class of medications is likely to be beneficial for a first episode of PHN. Because of the adverse events related to TCAs, most notably cardiac toxicity, they are not generally recommended for patients age 50 or older. Other SNRIs are safer choices.

Two topical analgesics also are efficacious for PHN: lidocaine 5% patch and capsaicin, especially the higher potency 8% formulation of the latter. Advantages of the topical analgesics include the absence of systemic adverse events, which many patients with PHN may be especially at risk for due to age or medical status. Because many patients with PHN-induced allodynia are unable to tolerate the heat sensation associated with capsaicin, the lidocaine patch is a better first-choice topical agent. Even if the topical analgesics provide only partial relief, this may help reduce the dose of oral pain medications needed.

Opioids can be beneficial for some patients with neuropathic pain but guidelines recommend that the medications discussed above should be tried first. The one opioid that appears to be more effective than others is tramadol. This is not surprising as it an opioid combined with an SNRI and most of the analgesia it provides appears to primarily be related to the latter action.

Next: Diabetic Peripheral Neuropathic Pain (DPNP)>>

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DPNP occurs in 10% to 20% of patients with diabetes mellitus (DM). Considering the growing population of Americans with DM, this is a significant number.⁴

As with PHN, the diagnosis of DPNP is usually straightforward because of its clear association with the underlying disease and the distribution of the pain, typically bilateral in the feet and lower extremities although it can also occur in the hands

The development of most often DPNP correlates with the level of control of DM-ie, it is less likely to occur when hyperglycemia is under better control. However, there are still many patients with well controlled DM who develop DPNP and those with poorly controlled DM who don't.⁵  Also, there is only a limited association found between the level of pain experienced and the degree of nerve damage present-many patients with diabetic neuropathy have no pain.

As with the other forms of neuropathic pain, the TCAs, SNRIs, and anticonvulsants are most likely to be effective for DPNP as are the lidocaine 5% patch and capsaicin.³ As many patients with DM also suffer from depression, consider treatment with a TCA (if the patient is younger than 50) or SNRI first.

Acupuncture, which carries no risks of systemic adverse effects, has also been reported to be beneficial for DPNP.⁶

Complex Regional Pain Syndrome (CRPS)

CRPS is one of the most painful of all chronic pain conditions. Although it was first identified during the Civil War more than 150 years ago, its etiology remains a mystery. It was initially named causalgia and this was subsequently replaced with reflex sympathetic dystrophy and then CRPS because of the questionable involvement of the sympathetic nervous system in many cases.

CRPS virtually always occurs in an extremity, although there are cases of men suffering it in their genitalia, following some form of trauma, including surgery, to the affected limb. There is little correlation between the severity of the trauma and the development of CRPS and although many predisposing factors have been proposed none have yet been proven to increase the likelihood CRPS will develop.

[[{"type":"media","view_mode":"media_crop","fid":"55267","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_1877140731918","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6912","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 166px; width: 250px; float: right;","title":"Tashaturango/Shutterstock.com","typeof":"foaf:Image"}}]]Many, if not most, cases of CRPS go undiagnosed as the pain is most often attributed to the trauma and the assumption is that it will resolve as the initial injury heals. Thus we still don't know for certain how frequent a disorder this is although at least one study suggests there may be as many 50,000 new cases in the US per year.¹

CRPS is essentially a clinical diagnosis. Allodynia should heighten your suspicion for the disorder in a patient who complains of pain.² Except for PHN, this occurs very rarely in most other pain problems. It is important to diagnose CRPS as soon as possible: the sooner it is diagnosed, the better the chances are of reducing the associated, often severe pain and preventing it from becoming chronic.

Because it is such a complicated disorder that can be so difficult to diagnose and treat, most primary care clinicians would probably prefer to refer patients they suspect of having CRPS to pain medicine specialists. Key is early recognition of the symptoms and rapid referral for treatment.

The treatment that appears to be of greatest importance is focusing on functional restoration of the affected limb primarily through physical and occupational therapies.

The medications that seem to provide the most relief are those used for other forms of neuropathic pain. Although the role of the sympathetic nervous system in CRPS remains questionable, sympathetic blocks may have some benefit if they are administered within the first 6 to 9 weeks after onset of the pain. Unfortunately, many patients with CRPS are still treated with sympathetic nerve blocks well into the course of the condition because the long delay between original injury and diagnosis is so common. There is little evidence, however, that they provide any benefit after the acute phase of injury.

Please click here for Chronic Pain Special Report Post-test

Please click on links below for Parts 1 to 3 of the Chronic Pain Practice Update for Primary Care Special Report

Part 1 Chronic Pain in Primary Care Practice Update - Overview and Pre-test

Part 2 Low Back Pain and Headache Pain Practice Update

Part 3 10 Opioid Myths and Facts

References:

1. van Hecke O, Austin SK, Khan RA, et al. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155:654-662.

2. Haanpaa M, Rice ASC, Rowbotham MC. Treating herpes zoster and postherpetic neuralgia. Pain Clinical Updates. 2015;23:1-8.

3. Finnerup NB, Attal N, Haroutonian S, et al. Pharmacotherapy for neuropthic pain in adults: a systematic review and meta-analysis. Lancet Neruol. 2015;14:162-173.

4.Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: epidemiology, natural history, early diagnosis, and treatment options. Pain Med. 2008;9:660-674.

5. Schreiber AK, Carina CFM, Reis RC, et al. Diabetic neuropathic pain: physiopathology and treatment. World J Diabetes. 2015;6:432-444.

6. Dimitrova A, Murchison C, et al. Effects of acupuncture on neuropathic pain: A systematic review and meta-analysis. Neurology; 2015;84; Supplement P3.306.