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Differential Diagnosis: Nociceptive and Neuropathic Pain
Bruce Nicholson, MD

Differential Diagnosis: Nociceptive and Neuropathic Pain

Bruce Nicholson, MD

Other factors that may increase the risk for herpes zoster infection include long-term corticosteroid use, chemotherapy, and radiation therapy.21 Race also appears to influence the risk for herpes zoster infection. Assessment of 3206 community-dwelling people older than 64 years of age indicated that blacks had an odds ratio of 0.25 versus whites for development of herpes zoster infection.25 Characteristics of acute infection associated with increased risk for PHN include greater severity of rash and acute pain, more severe sensory impairment in the affected dermatome, and psychologic distress.14

Symptoms of Herpes Zoster and Postherpetic Neuralgia

Acute Symptoms. Herpes zoster typically presents with a prodrome that lasts for 3 to 4 days and may include hyperesthesia, paresthesias, and/or burning dysesthesias or pruritus along the affected dermatome(s). Pain is the most common reason that patients with herpes zoster seek treatment. This pain is often described as burning or stinging and is generally unrelenting. The thoracic dermatomes are most often affected, but any dermatome can be involved. The ophthalmic division of the trigeminal nerve is the cranial nerve involved most often in patients with herpes zoster infection.21 These acute symptoms resolve shortly after rash healing in most patients, but a large minority of patients–particularly the elderly–develop symptoms characteristic of PHN.24

Postherpetic Neuralgia. In most patients, the diagnosis of PHN is not difficult, because they remember their symptomatic painful rash in the affected dermatome(s). Skin color changes and scarring may also assist in the diagnosis. There is no simple diagnostic test for PHN, and patients with this condition are identified on the basis of their clinical presentation and exclusion of other disease processes that may mimic PHN.22

Patients with PHN may present with a wide range of NP symptoms. These include ongoing pain that may be independent of any apparent external stimulus, which patients may notice more often at night or when their attention is not focused on some other activity. Patients with PHN are also likely to experience pain in response to light touch, even by their clothing (ie, allodynia). Some patients with PHN may also complain of lancinating pain (brief jolts of severe pain). Motor and autonomic symptoms are rare in PHN, but patients can occasionally present with pleural or bone pain, or a neurogenic bladder or rectum after a herpes zoster infection.26

It has been suggested that patients who develop PHN fall into 3 subtypes: (1) an "irritable nociceptor" group with minimal deafferentation and touch-evoked allodynia due to peripheral nociceptor input; (2) a deafferentation group with marked sensory loss and no allodynia; and (3) a deafferentation group with sensory loss and allodynia due to central reorganization.27 Patients with different PHN subtypes may respond differently to therapy for NP. For example, those with allodynic PHN have been predicted to receive the greatest benefit for local anesthesia, whereas this treatment may be less effective in the deafferentation group.27


Acute and chronic NP are common in patients with cancer. Results from an evaluation of 593 cancer patients treated by a pain service following World Health Organization guidelines for relief of cancer pain indicated that 380 patients presented with nociceptive pain, 32 presented with acute or chronic NP, and 181 presented with mixed (nociceptive and neuropathic) pain.28 Similarly, results from 187 consecutive patients with cancer and pain indicated that 55% had acute or chronic NP. The most frequent sites of neurologic injury were spinal nerves and the spinal cord, the cauda equina, the brachial and lumbosacral plexus, and peripheral nerves. In 93 of these patients, the pain was caused by ongoing neural injury; whereas, in 10 patients, the neural injury was long-standing and stable.29

Although it is clear that both cancer and its treatment can cause acute and chronic NP, the etiology of this pain is still not fully understood. However, results from recent studies of animal models of specific tumors have increased our insight into cancer-related acute and chronic NP.30 In this model, intramedullary injection and containment of osteolytic sarcoma cells into the mouse femur result in bone destruction and pain behavior similar to that of patients with bone cancer pain. The pain in the mouse model is associated with neurochemical reorganization of sensory neurons that innervate the tumor-bearing bone and in the spinal cord segments innervated by primary afferents supplying the cancerous bone. Most recently, it has been demonstrated that an antibody to nerve growth factor can decrease this pain and reduce the peripheral and central reorganization associated with it.31,32

Diagnosis of acute and chronic NP in the cancer patient is generally similar to that of other patients with pain. A prospective, cross-sectional, international, multicenter survey study carried out by the International Association for the Study of Pain Task Force on Cancer Pain has provided a comprehensive picture of pain in the cancer patient. Results from 1095 patients with severe cancer pain indicated that 92.5% had pain attributable to their cancer and 20.8% had treatment-associated pain. The average duration of pain in these patients was 5.9 months. Approximately two thirds of patients reported that the worst pain intensity during the day before the survey was =7 on a 10-point scale. Higher pain intensity was associated with the presence of breakthrough pain, somatic pain, and acute or chronic NP. Multivariate analysis indicated that the presence of breakthrough pain and somatic pain were associated with more intense pain. Overall, 71.6% of patients in this cohort had nociceptive pain and 39.7% had acute or chronic NP.33


Acute or chronic NP is very common, and it is often associated with diabetes, herpes zoster infection, and cancer. DPN is a very prevalent complication of long-standing diabetes, and recent results indicate that it affects more than one third of people with diabetes. PHN occurs less often, but its prevalence increases with age, and the number of cases might be expected to increase as the population ages. Cancer and its treatment are also common causes of acute and chronic NP. Patients with each of these conditions may present with a variety of symptoms, and results from at least 1 recent study suggest that DPN is substantially underdiagnosed.17 Careful attention to symptoms and patient history can facilitate diagnosis of both DPN and PHN.

Address correspondence to: Bruce Nicholson, MD, Penn State School of Medicine, Division of Pain Medicine, Lehigh Valley Hospital and Health Network, 1240 South Cedar Crest Blvd, Suite 307, Allentown, PA 18103. Email:

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