Confirming the presence of neuropathic pain in cancer patients
1. NeuPSIG grading system in clinical practice and clinical research.
Pain is one of the common symptoms of cancer. Approximately 50% of patients are seen for pain, and up to 75% of patients will suffer from pain in the advanced or progressive stages of cancer. Cancer patients typically experience two different types of pain, with an average of 20% originating from neuropathic pain; however, when the definition is expanded to include mixed neuropathic-injury pain, approximately 40% are neuropathic pain (NP).
Neuropathic pain in cancer patients will result in increased need for pain medications (especially strong opioids and adjuvant analgesics), decreased physical, cognitive, and social functioning, and greater impact on daily life. Unfortunately, under-treatment of cancer pain is common and is associated with a variety of factors, including fear of opioid use, inadequate pain assessment, and poor understanding of the underlying pathophysiologic mechanisms. This is very similar to the under-treatment of non-cancerous neuropathic pain. The difficulty in identifying neuropathic pain in cancer patients can be found in the development of the Edmonton grading system for cancer pain. In the original version of the system, cancer pain was classified as “injurious”, “neuropathic”, “mixed”, and other types. The updated version has reduced the number of categories, and only determines the presence of neuropathic pain based on clinical opinion.
The classification and diagnosis of neuropathic pain in cancer patients has been unclear. The presence of poor health and disability in both cancer and non-cancer populations with neuropathic pain suggests that there are inherent shortcomings in neuropathic pain that are not related to etiology. Therefore, it is extremely important to be able to effectively assess and diagnose neuropathic pain in cancer patients as a prerequisite for improved treatment approaches and outcomes. To examine the reliability of current methods for assessing neuropathic pain in cancer patients and to propose a standardized assessment protocol for confirming that neuropathic pain is indeed present in cancer patients by changing existing guidelines.
2. Reliability of existing neuropathic pain assessment methods
Although a definition of neuropathic pain was developed in 1994, the criteria for its diagnosis were not agreed upon until recently. in 2008, Treede et al. revised the definition of neuropathic pain as pain directly caused by injury or disease of the somatosensory nervous system. Treede et al. also developed a grading system to determine the presence or absence of neuropathic pain. This neuropathic pain grading system includes four specific criteria.
Criterion 1: Pain with a distinct neuroanatomical distribution.
Criterion 2: A definite history of injury or disease affecting the somatosensory system.
Criterion 3: Diagnostic testing confirms positive or negative sensory signs confined to the distribution of the injured nerve.
Criterion 4: Further diagnostic testing confirms an injury or disease that causes neuropathic pain.
Satisfying criteria 1 and 2 is considered suspicious for neuropathic pain. If criteria 3 or 4 are also met, the pain is “likely” to be neuropathic. If both criteria 3 and 4 are met, the diagnosis of neuropathic pain is confirmed.
This scoring system has been adopted in the revised Neuropathic Pain Special Interest Group (NeuPSIG) guidelines of the European Federation of Neurological Societies and the International Association for the Study of Pain. In both guidelines, the history of pain is considered to be the most important factor in the assessment of neuropathic pain. In both guidelines, history and bedside physical examination remain the key assessment criteria. There are still no standard guidelines for the implementation of a neuropathic pain grading system, especially for the assessment of criterion 3. This is the reason why this grading system is not widely adopted by clinical and scientific research.
The NeuPSIG guidelines, where the assessment of somatosensory function should include tactile, vibratory, cold, heat, and pain sensations, do not give specific implementation methods for these tests. in a recently published case report by Geber et al, the neuropathic pain grading system was used for the assessment of noncancerous pain. the conditions for meeting criteria 1 and 2 are relatively clear in the text, but it does not describe how to identify sensory abnormalities (criterion 3).
3. Application of the NeuPSIG grading system to cancer pain
3.1. Step 1: Identify the area of pain distribution (criterion 1)
Areas of pain distribution are drawn on a blank body map and analyzed for consistency with neuroanatomical distribution. The distribution of pain or nociceptive hypersensitivity can extend beyond the main innervated areas of peripheral nerves (taking into account the presence of involved pain or central sensitization), provided that it is consistent with the presentation of the underlying disease.
3.2. Step 2: Establishing a link between etiology and areas of pain distribution
In order to detect a history of injury or disease suggestive of the somatosensory system, it is necessary to clarify the etiology of pain by distinguishing between disease-related, treatment-related, or concomitant disease-related causes. In neuropathic cancer pain (NCP), a history of localized tumor growth invading or compressing neural tissue is often found. For example, spinal cord compression of a malignant tumor is a history of disease-related etiology, and receipt of chemotherapy with neurotoxic agents (e.g., paclitaxel and platinum) is a history of treatment-related etiology. The presence of somatosensory impairment or disease (e.g., diabetic neuropathy) in cancer patients or during treatment was considered a history of concomitant disease etiology.
3.3. Step 3: Specify sensory abnormalities (criterion 3)
Sensory abnormalities should be consistent with pain distribution. Therefore, it is necessary to draw the areas of sensory abnormalities on a separate body map. Table 1 describes the different methods used to test for sensory abnormalities. Only one sensory abnormality needs to be present to satisfy criterion 3. Sensory signs of afferent nerve block due to partial or total nerve injury are specific to neuropathic pain and therefore need to be described for sensory abnormalities. Both neuropathic and injurious pain can cause sensitization; therefore, the presence of sensitization does not indicate an injury or disease of the somatosensory system, but can provide useful information on pain mechanisms and/or alternative diagnoses. Patients may repeat sensory testing at a non-painful site (or a close corresponding dermatomal area) on the opposite side of the mirror image using their own control method to compare sensory test results from both sides of the body.
3.4. Step 4: Further diagnostic testing to detect injury or disease (Criterion 4)
If no imaging information is available in the history, further diagnostic imaging tests, such as MRI, CT, laboratory tests, and skin or nerve biopsies, may be performed to clarify the presence or absence of damage to the somatosensory system.
4. Future research directions
There is still a lack of unified diagnostic criteria for neuropathic pain in cancer patients, and further research on the accepted NCP classification system is still needed in the future. In this paper, we propose a standardized procedure for applying the NeuPSIG classification system to patients with cancer pain. It is important to clarify that NCP is a direct consequence of cancer damage to the somatosensory nervous system. Future studies need to distinguish between the presence of NCP or neuropathic pain in cancer patients (i.e., whether the pain is related to cancer treatment or to concomitant disease).
Table 1. Assessment of sensory abnormalities in NCP
Neurobiological pain
Mechanism
Positive findings on somatosensory examination
Clinical assessment methods
Negative sensory phenomena
Decreased sensitivity to…
Light touch with a cotton swab tip or soft brush (hypoesthesia)
Vibration with a tuning fork (hypoesthesia)
Deep pressure with the examiner’s thumb (hyperalgesia)
Pricking with a toothpick (hyperalgesia)
Low and high temperature cylinders or test tubes that cause pain (hyperalgesia)
Positive sensory phenomena
Increased sensitivity to…
Light touch with a cotton swab or soft brush (touch-induced pain)
Pricking with a toothpick (nociceptive hyperalgesia)
Low and high temperature cylinders or test tubes that cause pain (nociceptive hypersensitivity)
Deep pressure with the examiner’s thumb (nociceptive sensitization)