Elsevier

Neurologic Clinics

Volume 16, Issue 4, 1 November 1998, Pages 869-887
Neurologic Clinics

NEUROPATHIC PAIN IN THE CANCER PATIENT

https://doi.org/10.1016/S0733-8619(05)70102-XGet rights and content

Neuropathic pain remains as fascinating as the nervous system remains complex. Cancer provides an added layer to this complexity, contributing further to the heterogeneity of these syndromes. There have been several reviews9, 14, 29, 30 of neuropathic pain over the past several years with an emphasis on the need for further research.60 There are, however, few reviews of this subject with a focus on the specific issues and needs of cancer patients.59, 70 Key to a basic understanding of neuropathic pain is the recognition that changes in the nervous system after nerve injury may be different from changes after injury of nonneural structures.2 Why some patients who have nerve injury develop pain, whereas most do not, remains a critical question.75 Furthermore, why some painful symptoms resolve over time, whereas others continue indefinitely, is unknown. Treatment of these patients, as a result of the heterogeneity and uncertainty of disease, remains a challenge. Timely, diligent trials that are commonly performed in patients who do not have cancer is a luxury that is often not allowed in specific cancer populations, where progression of disease dictates the time one has to offer therapy.

Controlled studies in the cancer patient who has neuropathic pain are rare. As a result, treatment remains empirical, based on presumed dominant mechanisms.32 Insight into these processes is inferred through detailed clinical assessment and response to therapeutic trials. Presented here is a review of neuropathic pain with direct reference to the cancer patient, recognizing that the base of our knowledge regarding treatments comes largely from our experience in subjects who have cancer and controlled trials in patients who do not have cancer.

Section snippets

DEFINITIONS AND CLASSIFICATION OF SYNDROMES

Neuropathic pain has been defined by the International Association for the Study of Pain (IASP) Task Force as “Pain initiated or caused by a primary lesion or dysfunction in the nervous system.”66 Definitions of terms and clinical features used to describe neuropathic pain patients are essentially no different from those used to describe patients who do not have cancer. These are described in more detail in the article of this issue of Neurology Clinics on “Pain Assessment and Evaluation of

EPIDEMIOLOGY

Common syndromes in cancer patients (see Table 1) are the result of disease as well as of the sequelae of treatments. Many cancer patients are placed at risk for specific infections, such as Herpes Zoster (HZ), as a result of their depressed immune status. Otherwise, the major treatment-related syndromes evolve after nerve injury associated with chemotherapy, radiation therapy, or surgery. Age at the time of nerve injury may play a significant role as recognized in a higher prevalence of

PATHOPHYSIOLOGY

Mechanisms to explain the spontaneous and the evoked generation of painful sensations after neural injury are numerous.9 Advances in our understanding of neural changes after nerve injury come mostly from studies looking at specific animal behavior after neural injury, 10, 16 as well as from human studies of pain and sensory changes after dermal injection of capsaicin.52

Events leading to both peripheral and central sensitization appear critical in the development of specific neuropathic pain

CLINICAL ASSESSMENT

Pain as a symptom of ongoing disease needs to be separated from neuropathic pain, which, by definition, may persist despite any noxious cause. As such, neuropathic pain becomes the pain diagnosis independent of the underlying noxious cause. As with the assessment of all pain syndromes, a comprehensive history and examination is essential.31 Diagnostic studies, including imaging of relevant neural structures are often necessary to confirm clinical diagnosis38 and to rule out recurrent disease.

TREATMENT

Treatment of pain, as with any symptom, begins with a proper diagnosis. Defining the extent of disease and ruling out the recurrence of disease in patients who have been treated remains the first order of business. When neural compression by tumor is the cause of pain, treatment of the underlying cancer often remains the best treatment. Reducing tumor compression of a nerve through surgery and radiation therapy or chemotherapy or both should always be considered, even if cure of the disease is

Antidepressants

Antidepressants are effective for a variety of chronic pain syndromes, including neuropathic pain.64 In a metaanalysis of placebo-controlled trials, antidepressants appeared most effective in the treatment of pain associated with the following syndromes: diabetic neuropathy, PHN, trigeminal neuralgia, and migraine and tension headaches.67 In studies of central poststroke or neuropathic pain, higher serum levels of amitriptyline or nortriptyline correlate with analgesia.53 Other studies do not

SUMMARY

Treatment of neuropathic pain is empirical with a rational, stepwise approach based on effective therapies within distinct drug classes (Table 4). The therapies for neuropathic pain in cancer patients are no different from those available to the noncancer patient. Each class of drugs has a presumed, distinct mechanism of action. Opioids, TCAs, antiarrythmics, and anticonvulsants, form the base of most treatment algorithms and are most often effective when used in various combinations. Topical

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    Address reprint requests to Robert R. Allen, MD, Associate Director, Clinical Research, Astra USA, 50 Otis Street, Westborough, MA 01581, [email protected]

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