Michael I. Bennett

The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs

&NA; This study describes the development and validation of a novel tool for identifying patients in whom neuropathic mechanisms dominate their pain experience. The Leeds assessment of neuropathic symptoms and signs (LANSS) Pain Scale is based on analysis of sensory description and bedside examination of sensory dysfunction, and provides immediate information in clinical settings. It was developed in two populations of chronic pain patients. In the first (n=60), the use of sensory descriptors and questions were compared in patients with nociceptive and neuropathic pain, combined with an assessment of sensory function. This data was used to derive a seven item pain scale, consisting of grouped sensory description and sensory examination with a simple scoring system. The LANSS Pain Scale was validated in a second group of patients (n=40) by assessing discriminant ability, internal consistency and agreement by independent raters. Clinical and research applications of the LANSS Pain Scale are discussed.

NeuPSIG guidelines on neuropathic pain assessment

&NA; This is a revision of guidelines, originally published in 2004, for the assessment of patients with neuropathic pain. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system either at peripheral or central level. Screening questionnaires are suitable for identifying potential patients with neuropathic pain, but further validation of them is needed for epidemiological purposes. Clinical examination, including accurate sensory examination, is the basis of neuropathic pain diagnosis. For more accurate sensory profiling, quantitative sensory testing is recommended for selected cases in clinic, including the diagnosis of small fiber neuropathies and for research purposes. Measurement of trigeminal reflexes mediated by A‐beta fibers can be used to differentiate symptomatic trigeminal neuralgia from classical trigeminal neuralgia. Measurement of laser‐evoked potentials is useful for assessing function of the A‐delta fiber pathways in patients with neuropathic pain. Functional brain imaging is not currently useful for individual patients in clinical practice, but is an interesting research tool. Skin biopsy to measure the intraepidermal nerve fiber density should be performed in patients with clinical signs of small fiber dysfunction. The intensity of pain and treatment effect (both in clinic and trials) should be assessed with numerical rating scale or visual analog scale. For future neuropathic pain trials, pain relief scales, patient and clinician global impression of change, the proportion of responders (50% and 30% pain relief), validated neuropathic pain quality measures and assessment of sleep, mood, functional capacity and quality of life are recommended.

A classification of chronic pain for ICD-11

Chronic pain has been recognized as pain that persists past normal healing time5 and hence lacks the acute warning function of physiological nociception.35 Usually pain is regarded as chronic when it lasts or recurs for more than 3 to 6 months.29 Chronic pain is a frequent condition, affecting an estimated 20% of people worldwide6,13,14,18 and accounting for 15% to 20% of physician visits.25,28 Chronic pain should receive greater attention as a global health priority because adequate pain treatment is a human right, and it is the duty of any health care system to provide it.4,13 The current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO) includes some diagnostic codes for chronic pain conditions, but these diagnoses do not reflect the actual epidemiology of chronic pain, nor are they categorized in a systematic manner. The ICD is the preeminent tool for coding diagnoses and documenting investigations or therapeutic measures within the health care systems of many countries. In addition, ICD codes are commonly used to report target diseases and comorbidities of participants in clinical research. Consequently, the current lack of adequate coding in the ICD makes the acquisition of accurate epidemiological data related to chronic pain difficult, prevents adequate billing for health care expenses related to pain treatment, and hinders the development and implementation of new therapies.10,11,16,23,27,31,37 Responding to these shortcomings, the International Association for the Study of Pain (IASP) contacted the WHO and established a Task Force for the Classification of Chronic Pain. The IASP Task Force, which comprises pain experts from across the globe,19 has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the ICD. The goal is to create a classification system that is applicable in primary care and in clinical settings for specialized pain management. A major challenge in this process was finding a rational principle of classification that suits the different types of chronic pain and fits into the general ICD-11 framework. Pain categories are variably defined based on the perceived location (headache), etiology (cancer pain), or the primarily affected anatomical system (neuropathic pain). Some diagnoses of pain defy these classification principles (fibromyalgia). This problem is not unique to the classification of pain, but exists throughout the ICD. The IASP Task Force decided to give first priority to pain etiology, followed by underlying pathophysiological mechanisms, and finally the body site. Developing this multilayered classification was greatly facilitated by a novel principle of assigning diagnostic codes in ICD-11, termed “multiple parenting.” Multiple parenting allows the same diagnosis to be subsumed under more than 1 category (for a glossary of ICD terms refer to Table ​Table1).1). Each diagnosis retains 1 category as primary parent, but is cross-referenced to other categories that function as secondary parents. Table 1 Glossary of ICD-11 terms. The new ICD category for “Chronic Pain” comprises the most common clinically relevant disorders. These disorders were divided into 7 groups (Fig. ​(Fig.1):1): (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain. Experts assigned to each group are responsible for the definition of diagnostic criteria and the selection of the diagnoses to be included under these subcategories of chronic pain. Thanks to Bedirhan Ustun and Robert Jakob of the WHO, these pain diagnoses are now integrated in the beta version of ICD-11 (http://id.who.int/icd/entity/1581976053). The Task Force is generating content models for single entities to describe their clinical characteristics. After peer review overseen by the WHO Steering Committee,39 the classification of chronic pain will be voted into action by the World Health Assembly in 2017. Figure 1 Organizational chart of Task Force, IASP, and WHO interactions. The IASP Task Force was created by the IASP council and its scope defined in direct consultation of the chairs (R.D.T. and W.R.) with WHO representatives in 2012. The Task Force reports to ... 2. Classification of chronic pain Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized. Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment. 2.1. Chronic primary pain Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. This is a new phenomenological definition, created because the etiology is unknown for many forms of chronic pain. Common conditions such as, eg, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective.

Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community.

ObjectivesTo assess the health and quality of life associated with chronic pain of predominantly neuropathic origin (POPNO) on health and daily activity in the general population. MethodsThe Self-complete Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire, recently validated for identifying pain of predominantly neuropathic origin, was sent to 6000 adults identified from general practices in the United Kingdom, along with chronic pain identification and severity questions, the Brief Pain Inventory (BPI), the Neuropathic Pain Scale, and the SF-36 general health questionnaire. ResultsWith a corrected response rate of 52%, 3 groups of respondents were identified: those without chronic pain (“No Chronic Pain” group, n=1537); those with chronic pain who were S-LANSS positive indicating the presence of POPNO (“Chronic POPNO” group, n =241); and those with chronic pain who were S-LANSS negative [“Chronic Pain (non-POPNO)” group, n=1179]. The chronic POPNO group reported higher pain severity and had significantly poorer scores for all interference items of the BPI than those with chronic pain (non-POPNO). Mean scores from the Neuropathic Pain Scale were also significantly higher for the Chronic POPNO group. There were significant differences between the groups in all domains of the SF-36, with the Chronic POPNO group reporting the worst health. After adjusting for pain severity, age, and sex, the chronic POPNO group was still found to have poorer scores than the other Chronic Pain (non-POPNO) group in all domains of the SF-36 and all interference items in the BPI, indicating poorer health and greater disability. DiscussionThis study confirms the importance of identifying neuropathic pain in the community, and the need for multidimensional management strategies that address all aspects of health.

Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review.

Summary One in 5 cancer pains are neuropathic, and 2 in 5 patients have neuropathic pain. Standard approaches to assess cancer neuropathic pain are needed. Abstract Pain in cancer patients remains common and is often associated with insufficient prescribing of targeted analgesia. An explanation for undertreatment could be the failure to identify neuropathic pain mechanisms, which require additional prescribing strategies. We wanted to identify the prevalence of neuropathic mechanisms in patients with cancer pain to highlight the need for detailed assessment and to support the development of an international classification system for cancer pain. We searched for studies that included adult and teenage patients (age above 12 years), with active cancer and who reported pain, and in which a clinical assessment of their pain had been made. We found 22 eligible studies that reported on 13,683 patients. Clinical assessment methods varied, and only 14 studies reported confirmatory testing for either sensory abnormality or diagnostic lesion to corroborate a diagnosis of neuropathic pain. We calculated that the prevalence of patients with neuropathic pain (95% confidence interval) varied from a conservative estimate of 19% (9.4% to 28.4%) to a liberal estimate of 39.1% (28.9% to 49.5%) when patients with mixed pain were included. The prevalence of pain with a neuropathic mechanism (95% confidence interval) ranged from a conservative estimate of 18.7% (15.3% to 22.1%) to a liberal estimate of 21.4% (15.2% to 27.6%) of all recorded cancer pains. The proportion of pain caused by cancer treatment was higher in neuropathic pain compared with all types of cancer pain. A standardised approach or taxonomy used for assessing neuropathic pain in patients with cancer is needed to improve treatment outcomes.

Assessment of Neuropathic Pain in Primary Care

Management of patients presenting with chronic pain is a common problem in primary care. Essentially, the classification of chronic pain falls into 3 broad categories: (1) pain owing to tissue disease or damage (nociceptive pain), (2) pain caused by somatosensory system disease or damage (neuropathic pain), and (3) pain without a known somatic background. Key challenges in developing a targeted holistic approach to treatment include appropriate diagnosis of the cause or causes of pain; identifying the type of pain and assessing the relative importance of its various components; and determining appropriate treatment. In clinical examination, sensory abnormalities are the crucial findings leading to a diagnosis of neuropathic pain, for which pharmacotherapy with antidepressants and anticonvulsants represents the cornerstone of medical treatment. Chronic neuropathic pain is underrecognized and undertreated, yet primary care physicians are uniquely placed on the frontlines of patient management, where they can play a pivotal role in treatment and prevention through diagnosis, therapy, follow-up, and referral. This review provides guidance in understanding and identifying the neuropathic contribution to pain presenting in primary care; assessing its severity through patient history, physical examination, and appropriate diagnostic tests; and establishing a rational treatment plan.

Gabapentin in the treatment of neuropathic pain.

This paper reviews the pharmacology and clinical effectiveness of gabapentin in the treatment of neuropathic pain. Gabapentin has antihyperalgesic and antiallodynic properties but does not have significant actions as an anti-nociceptive agent. Its mechanisms of action appear to be a complex synergy between increased GABA synthesis, non-NMDA receptor antagonism and binding to the α2δ subunit of voltage dependent calcium channels. The latter action inhibits the release of excitatory neurotransmitters. Clinically, several large randomized controlled trials have demonstrated its effectiveness in the treatment of a variety of neuropathic pain syndromes. Patients with neuropathic pain can expect a mean reduction in pain score of 2.05 points on an 11 point numerical rating scale compared with a reduction of 0.94 points if they had taken the placebo. Around 30% of patients can expect to achieve more than 50% pain relief and a similar number will also experience minor adverse events; the most common of which are somnolence and dizziness. In patients with neuropathic pain due to cancer, higher response rates might be observed with gabapentin when administered with opioids because of a synergistic interaction.

How effective are patient-based educational interventions in the management of cancer pain? Systematic review and meta-analysis

ABSTRACT This review aimed to quantify the benefit of patient‐based educational interventions in the management of cancer pain. We undertook a systematic review and meta‐analysis of experimentally randomised and non‐randomised controlled clinical trials identified from six databases from inception to November 2007.Two reviewers independently selected trials comparing intervention (formal instruction on cancer pain and analgesia on an individual basis using any medium) to usual care or other control in adults with cancer pain. Methodological quality was assessed, and data extraction undertaken by one reviewer with a second reviewer checking for accuracy. We used random effects model to combine the effect estimates from studies. Main outcome measures were effects on knowledge and attitudes towards cancer pain and analgesia, and pain intensity. Twenty‐one trials (19 randomised) totalling 3501 patients met inclusion criteria, and 15 were included in the meta‐analysis. Compared to usual care or control, educational interventions improved knowledge and attitudes by half a point on 0–5 rating scale (weighted mean difference 0.52, 95% confidence interval 0.04–1.0), reduced average pain intensity by over one point on 0–10 rating scale (WMD −1.1, −1.8 to −0.41) and reduced worst pain intensity by just under one point (WMD −0.78, −1.21 to −0.35). We found equivocal evidence for the effect of education on self‐efficacy, but no significant benefit on medication adherence or on reducing interference with daily activities. Patient‐based educational interventions can result in modest but significant benefits in the management of cancer pain, and are probably underused alongside more traditional analgesic approaches.

Can pain can be more or less neuropathic? Comparison of symptom assessment tools with ratings of certainty by clinicians

Abstract Chronic pain is generally regarded as being divided into two mutually exclusive pain mechanisms: nociceptive and neuropathic. Recently, this dichotomous approach has been questioned and a model of chronic pain being ‘more or less neuropathic’ has been suggested. To test whether such a spectrum exists, we examined responses by patients with chronic pain to validated neuropathic pain assessment tools and compared these with ratings of certainty about the neuropathic origin of pain by their specialist pain physicians. We examined 200 patients (100 each with nociceptive and neuropathic pain) and administered the self‐complete Leeds Assessment of Neuropathic Symptoms and Signs (S‐LANSS score) and the Neuropathic Pain Scale (NPS). Clinicians were asked to rate their certainty of the presence of neuropathic pain mechanisms on a 100 mm visual analogue scale (VAS) (0 = ‘not at all neuropathic in origin’ to 100 = ‘completely neuropathic in origin’). The whole sample was divided into tertiles based on ascending ratings of diagnostic certainty by clinicians using the VAS and labelled ‘unlikely’, ‘possible’ and ‘definite’ neuropathic pain. There were significant differences in median S‐LANSS and NPS composite scores between all tertile groups. There were also significant differences between many S‐LANSS and NPS item scores between groups. We have shown that higher scores on both the S‐LANSS and the NPS are indicative of greater clinician certainty of neuropathic pain mechanisms being present. These data support the theoretical construct that pain can be more or less neuropathic and that pain of predominantly neuropathic origin may be a useful clinical concept.

Diagnosis and management of neuropathic pain

#### Summary points Neuropathic pain arises from damage, or pathological change, in the peripheral or central nervous system. It is usually a chronic condition that can be difficult to treat because standard treatment with conventional analgesics does not typically provide effective relief of pain. Patients with neuropathic pain commonly present to primary care professionals, but making a diagnosis may be difficult. Neuropathic pain is usually associated with substantially greater impairment of quality of life compared with other types of chronic pain, and the disorder is a large cost burden on healthcare services. In this review, we provide an overview of published evidence to help clinicians recognise and manage patients with neuropathic pain. A group of specialists of the International Association for the Study of Pain defines neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.”1 In contrast to inflammatory or nociceptive pain, which is caused by actual tissue damage or potentially tissue damaging stimuli, neuropathic pain is produced either by damage to, or pathological change in, the peripheral or central nervous system, the system that normally signals pain. As such, the term neuropathic pain represents a varying set of symptoms rather than a single diagnosis. Damage to the somatosensory system can provoke a range of responses; an absence of sensation and pain is probably a more common response than new onset of …