2. Development Committee
Mario H. Cardiel, MD, MSc
Rheumatologist
Morelia, Mexico
Andrei Danilov, MD, DSc
Neurologist
Moscow, Russia
Smail Daoudi, MD
Tizi Ouzou, Algeria
João Batista S. Garcia, MD, PhD
Anesthesiologist
São Luis, Brazil
Yuzhou Guan, MD
Beijing, China
Jianhao Lin, MD
Orthopedist
Beijing, China
Supranee Niruthisard, MD
Anesthesiologist, Pain Specialist
Bangkok, Thailand
Germán Ochoa, MD
Orthopedist, Spine Surgeon and Pain Specialist
Bogotá, Colombia
Milton Raff, MD, BSc
Consultant Anesthetist
Cape Town, South Africa
Raymond L. Rosales, MD, PhD
Neurologist
Manila, Philippines
Ammar Salti, MD
Consultant Anesthetist
Abu Dhabi, United Arab Emirates
Jose Antonio San Juan, MD
Orthopedic Surgeon
Cebu City, Philippines
Xinping Tian, MD
Rheumatologist
Beijing, China
Işin Ünal-Çevik, MD, PhD
Neurologist, Neuroscientist and Pain Specialist
Ankara, Turkey
Speaker’s Notes
Please acknowledge the members of the development committee.
This program was sponsored by Pfizer Inc.

3. Learning Objectives
After completing this module, participants will be able to:
Explain the pathophysiology of neuropathic pain
Discuss the prevalence of neuropathic pain
Apply a simple diagnostic technique for the diagnosis of neuropathic pain
Understand the impact of neuropathic pain and its comorbidities on patient functioning and quality of life
Select appropriate pharmacological and non-pharmacological strategies for the management of neuropathic pain
Know when to refer patients to specialists
Speaker’s Notes
Review the learning objectives for this session. Ask the participants if they have any additional goals.

4. Table of Contents What is neuropathic pain?
How common is neuropathic pain?
How can neuropathic pain be differentiated from nociceptive pain?
What is the impact of neuropathic pain?
How should neuropathic pain be treated based on its pathophysiology?
Speaker’s Notes
Please acknowledge the members of the development committee.

5. Pathophysiological Classification of Pain
Central sensitization/ dysfunctional pain
Multiple pain mechanisms may coexist
(mixed pain)
Nociceptive pain
Somatic
Visceral
Neuropathic pain
Peripheral
Central
Speaker’s Notes
This slide illustrates three broad categories of pain: central sensitization/dysfunctional, neuropathic and nociceptive pain. It should also be noted that many conditions feature more than one type of pain, and are thus termed ‘mixed pain’ states.
Nociceptive pain is an appropriate physiologic response that occurs when specific peripheral sensory neurons (nociceptors) respond to noxious stimuli. Nociceptive pain has a protective role because it elicits reflex and behavioral responses that keep tissue damage to a minimum. Nociceptive pain may be somatic or visceral in origin. Somatic pain, such as gout, osteoarthritis and trauma-induced pain, originates with the musculoskeletal or cutaneous nociceptors and is often well localized. Visceral pain, such as dysmenorrhea or acute pancreatitis, originates in nociceptors located in the hollow organs and smooth muscles; it is often referred.
Neuropathic pain has been defined by the International Association for the Study of Pain as “Pain caused by a lesion or disease of the somatosensory nervous system.” Depending on where the lesion or dysfunction occurs within the nervous system, neuropathic pain can be peripheral in origin (as in painful diabetic peripheral neuropathy and postherpetic neuralgia) or central in origin (for example, neuropathic pain associated with stroke or spinal cord injury).
Central sensitization/dysfunctional pain is defined as “Hypersensitivity of the pain system such that normally innocuous inputs can activate and perceptual responses to noxious inputs are exaggerated, prolonged and spread widely”. Some common examples for this pain type are: fibromyalgia, temporomandibular joint disorder, chronic migraine/tension type headache, interstitial cystitis, irritable bowel syndrome and complex regional pain syndrome.
There are cases in which more than one type of pain pathophysiology exist (mixed pain). For example, in a lumbar herniated disc patient with radiculopathy, it is common to experience both nociceptive/inflammatory pain, felt around the low back area with movement, and neuropathic pain, felt in the distribution territory of the effected root (lower extremity).
References
Freynhagen R, Baron R. The evaluation of neuropathic components in low back pain. Curr Pain Headache Rep 2009; 13(3):
Jensen TS et al. A new definition of neuropathic pain. Pain 2011; 152(10):
Julius D et al. In: McMahon SB, Koltzenburg M (eds). Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier; London, UK: 2006.
Ross E. Moving towards rational pharmacological management of pain with an improved classification system of pain. Expert Opin Pharmacother 2001; 2(1):
Webster LR. Breakthrough pain in the management of chronic persistent pain syndromes. Am J Manag Care 2008; 14(5 Suppl 1):S
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152(3 Suppl):S2-15.
Freynhagen R, Baron R. Curr Pain Headache Rep 2009; 13(3):185-90; Jensen TS et al. Pain 2011; 152(10):2204-5; Julius D et al. In: McMahon SB, Koltzenburg M (eds). Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier; London, UK: 2006; Ross E. Expert Opin Pharmacother 2001; 2(1): ; Webster LR. Am J Manag Care 2008; 14(5 Suppl 1):S116-22; Woolf CJ. Pain 2011; 152(3 Suppl):S2-15.

6. What is neuropathic pain?
Pain caused by a lesion or disease of the somatosensory nervous system
Peripheral Neuropathic Pain
Pain caused by a lesion or disease of the peripheral somatosensory nervous system
Central Neuropathic Pain
Pain caused by a lesion or disease of the central somatosensory nervous system
Speaker’s Notes
The International Association for the Study of Pain (IASP)’s definition of neuropathic pain as “Pain caused by a lesion or disease of the somatosensory nervous system”
Note: Neuropathic pain is a clinical description (and not a diagnosis) which requires a demonstrable lesion or a disease that satisfies established neurological diagnostic criteria. The term lesion is commonly used when diagnostic investigations (e.g. imaging, neurophysiology, biopsies, lab tests) reveal an abnormality or when there was obvious trauma. The term disease is commonly used when the underlying cause of the lesion is known (e.g. stroke, vasculitis, diabetes mellitus, genetic abnormality). Somatosensory refers to information about the body per se including visceral organs, rather than information about the external world (e.g., vision, hearing, or olfaction). The presence of symptoms or signs (e.g., touch-evoked pain) alone does not justify the use of the term neuropathic. Some disease entities, such as trigeminal neuralgia, are currently defined by their clinical presentation rather than by objective diagnostic testing. Other diagnoses such as postherpetic neuralgia are normally based upon the history. It is common when investigating neuropathic pain that diagnostic testing may yield inconclusive or even inconsistent data. In such instances, clinical judgment is required to reduce the totality of findings in a patient into one putative diagnosis or concise group of diagnoses.
Depending on where the lesion or dysfunction occurs in the nervous system, neuropathic pain can be peripheral or central in origin. Causes of peripheral neuropathic pain include post-surgical and post-traumatic nerve injury, diabetic peripheral neuropathy, postherpetic neuralgia etc. Causes of central neuropathic pain are: post-stroke pain, multiple sclerosis and spinal cord injuries, etc.
Reference
International Association for the Study of Pain. IASP Taxonomy, Changes in the 2011 List. Available at: Accessed: July 15, 2013.
International Association for the Study of Pain. IASP Taxonomy, Changes in the List. Available at: Accessed: July 15, 2013.

7. Nociceptive vs. Neuropathic Pain
Usually aching or throbbing and well-localized
Usually time-limited (resolves when damaged tissue heals), but can be chronic
Generally responds to conventional analgesics
Pain often described as tingling, shock-like, and burning – commonly associated with numbness
Almost always a chronic condition
Responds poorly to conventional analgesics
Speaker’s Notes
With nociceptive pain, the painful region is typically localized to the site of injury and the pain is often described as throbbing, aching or pressure-like. Nociceptive pain is usually time limited and resolves when the damaged tissue heals (e.g., bone fractures, burns, and bruises). Although nociceptive pain is generally self-limiting, it can be chronic, as in osteoarthritis. Treatment with conventional analgesics is usually appropriate.
Neuropathic pain is frequently described as a ‘shooting’, ‘electric shock-like’ or burning’ pain, commonly associated with ‘tingling’ and/or ‘numbness’. The painful region may not necessarily be the same as the site of injury. Pain occurs in the neurological territory of the affected structure (nerve, root, spinal cord, brain). In peripheral neuropathic pain, it is in the territory of the affected nerve or nerve root. In central neuropathic pain, it is related to the site of the lesion in the spinal cord or brain. Neuropathic pain is almost always a chronic condition and responds poorly to conventional analgesics.
References
Dray A. Neuropathic pain: emerging treatments. Br J Anaesth 2008; 101(1):48-58.
Felson DT. Developments in the clinical understanding of osteoarthritis. Arthritis Res Ther 2009; 11(1):203.
International Association for the Study of Pain. IASP Taxonomy. Available at: pain.org/AM/Template.cfm?Section=Pain_Definitions. Accessed: July 15, 2013.
McMahon SB, Koltzenburg M (eds). Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier; London, UK: 2006.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152(3 Suppl):S2-15.
Dray A. Br J Anaesth 2008; 101(1):48-58; Felson DT. Arthritis Res Ther 2009; 11(1):203; International Association for the Study of Pain. IASP Taxonomy. Available at: Accessed: July 15, 2013; McMahon SB, Koltzenburg M (eds). Wall and Melzack’s Textbook of Pain. 5th ed. Elsevier; London, UK: 2006; Woolf CJ. Pain 2011; 152(3 Suppl):S2-15.

8. Neuropathic Pain Is Characterized by Changes in Pain Response to Painful Stimuli10 8 6 4 2
Hyperalgesia
(increased response to a stimulus that is normally painful)
Normal
pain response
Pain intensity
Allodynia
(pain due to stimulus that does not normally provoke pain)
Injury
Response after injury
Speaker’s Notes
This animated slide illustrates what happens to pain response following nerve injury.
Left-click or arrow down in presentation mode to show the next item in the animation sequence. Please wait for the animation to finish running before clicking for the next item:
The normal pain response curve (that appears with upon first showing slide) shows zero pain intensity with lower intensity stimuli (e.g., light touch does not normally elicit pain; it is an innocuous stimuli. As stimulus intensity increases (e.g., squeezing or pinching harder), one begins to feel pain with increasing intensity.
Following nerve injury, the pain response curve shifts to the left.
The dotted line representing a fixed stimulus intensity bisects both pain response curves. In the normal pain response, this level of stimulus would cause a low level of pain. With a left shift of the response curve following injury, this same level of stimulus would cause a much higher level of pain.
This is the definition of “hyperalgesia”, a heightened response to a stimulus that would normally evoke pain.
Normally innocuous stimuli (blue shaded region) now become painful. This is the definition of “allodynia”, a painful response to a stimulus that is not normally painful.
Reference
Gottschalk A et al. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician 2001; 63(10):
Stimulus intensity
Adapted from: Gottschalk A et al. Am Fam Physician 2001; 63(10):

9. Pathophysiology of Neuropathic Pain
Peripheral mechanisms
Membrane hyperexcitability
Ectopic discharges
Transcriptional changes
Central mechanisms
Hyperexcitability
Sensitization
Peripheral
Central
Neuropathic pain
Loss of inhibitory controls
Speaker’s Notes
Pain arising as a direct consequence of a lesion or disease affecting the somatosensory system is defined as “neuropathic pain”.
This slide illustrates the main mechanisms underlying the development of neuropathic pain.
Peripheral mechanisms of neuropathic pain include membrane hyperexcitability in the nociceptive neurons, ectopic discharges along sensory nerves, which may lead to transcriptional changes in the dorsal root ganglia (peripheral sensitization). Peripheral mechanisms can trigger changes within the central nervous system (central mechanisms) as well.
Central mechanisms in the spinal cord include increased excitability in the dorsal horn neurons, sprouting of non-nociceptive myelinated A-beta-afferents in the dorsal horn that form new connections with the nociceptive neurons in the laminae I and II, and loss of inhibitory controls (disinhibition). Central mechanisms in the supraspinal systems include hyperexcitability and changes in synaptic activity and reorganization within the brainstem nuclei, thalamus and the brain cortex associated with pain matrix (central sensitization).
References
Moisset X, Bouhassira D. Brain imaging of neuropathic pain. Neuroimage 2007; 37(Suppl 1):S80-8.
Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002; 5(Suppl):
Reorganization
Moisset X, Bouhassira D. Neuroimage 2007; 37(Suppl 1):S80-8; Scholz J, Woolf CJ. Nat Neurosci 2002; 5(Suppl):

10. Neuropathic Pain is Prevalent Across a Range of Different Conditions
% affected by peripheral neuropathic pain
Condition
% affected by central neuropathic pain
11–26%1
Diabetes
Stroke
8%9
~33%2
Cancer
Spinal cord injury
75%10
35–53%3–5
HIV
Multiple sclerosis
~55%11
20–43% of mastectomy patients6,7
Post-surgical
Speaker’s Notes
This slide contains an animated build to detail neuropathic pain prevalence data in different pain states. Clicking on this slide will cause subsequent components of this build to appear.
Neuropathic pain is highly prevalent across a range of different conditions. This slide lists examples of some of the underlying causes of neuropathic pain (divided according to peripheral and central neuropathic pain) and provides prevalence data for each:
Diabetes: 11–26% (best estimate 15%) of patients with diabetes develop painful diabetic peripheral neuropathy1
Cancer: neuropathic pain affects approximately one-third (33%) of cancer patients2
HIV: distal sensory polyneuropathy may be present in 35–55% of patients with HIV3-5
Post-surgical pain: neuropathic pain may be present in 20–43% of mastectomy patients6,7
Radiculopathy (low back pain): neuropathic pain affects up to 37% of patients with chronic low back pain8
Postherpetic neuralgia: estimated to occur in 7–27% of patients who develop shingles. Prevalence increases with age as 25–50% of patients >50 years with herpes zoster develop postherpetic neuralgia.12
Stroke: neuropathic pain affects 8% of poststroke patients9
Spinal cord injury: neuropathic pain affects 75% of patients with spinal cord injury10
Multiple sclerosis: neuropathic pain affects ~55% of patients with multiple sclerosis11
References
Sadosky A et al. A review of the epidemiology of painful diabetic peripheral neuropathy, postherpetic neuralgia, and less commonly studied neuropathic pain conditions. Pain Pract 2008; 8(1):45-56.
Davis MP, Walsh D. Epidemiology of cancer pain and factors influencing poor pain control. Am J Hosp Palliat Care 2004; 21(2):
So YT et al. Peripheral neuropathy associated with acquired immunodeficiency syndrome. Prevalence and clinical features from a population- based survey. Arch Neurol 1988; 45(9):945-8.
Schifitto G et al. Incidence of and risk factors for HIV-associated distal sensory polyneuropathy..Neurology 2002; 58(12):
Morgello S et al. HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank. Arch Neurol 2004; 61(4):
Stevens PE et al. Prevalence, characteristics, and impact of postmastectomy pain syndrome: an investigation of women's experiences. Pain 1995; 61(1):61-8.
Smith WC et al. A retrospective cohort study of post mastectomy pain syndrome. Pain 1999; 83(1):91-5.
Freynhagen R et al. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin 2006; 22(10):
Andersen G et al. Incidence of central post-stroke pain. Pain 1995; 61(2):
Siddall PJ et al. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain 2003; 103(3):
Rae-Grant AD et al. Sensory symptoms of multiple sclerosis: a hidden reservoir of morbidity. Mult Scler 1999; 5(3):
Up to 37%8
Chronic low back pain
7–27% of patients with herpes zoster1
Postherpetic neuralgia
HIV = human immunodeficiency virus
1. Sadosky A et al. Pain Pract 2008; 8(1):45-56; 2. Davis MP, Walsh D. Am J Hosp Palliat Care 2004; 21(2):137-42; 3. So YT et al. Arch Neurol 1988; 45(9):945-8; 4. Schifitto G et al. Neurology 2002; 58(12):1764-8; 5. Morgello S et al. Arch Neurol 2004; 61(4):546-51; 6. Stevens PE et al. Pain 1995; 61(1):61-8; 7. Smith WC et al. Pain 1999; 83(1):91-5; 8. Freynhagen R et al. Curr Med Res Opin 2006; 22(10): ; 9. Andersen G et al. Pain 1995; 61(2):187-93; 10. Siddall PJ et al. Pain. 2003; 103(3):249-57; 11. Rae-Grant AD et al. Mult Scler 1999; 5(3):

11. what proportion of your patients suffer from neuropathic pain?
Discussion Question
what proportion of your patients suffer from neuropathic pain?
Speaker’s Notes
Ask the question shown on the slide to participants to stimulate discussion.

12. 5–20% of the General Population May Suffer from Neuropathic Pain
Summary of Selected Prevalence Studies
Speaker’s Notes
It is estimated that 5–20% of the general population may suffer from chronic neuropathic pain.
This slide summarizes the results of selected prevalence studies, showing the prevalence of both chronic pain and chronic neuropathic pain in the studied populations. These studies cover a wide variety of geographic areas including Brazil, Canada, France, Germany, Libya, Morocco and the United Kingdom.
de Moras Vieira and colleagues surveyed 1597 people in São Luís, Brazil and determined that 10% suffered from chronic pain with neuropathic characteristics.
Torrance et al mailed questionnaires that included the self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) to a random sample of 6000 adults from six family practices in Aberdeen, Leeds and London in the United Kingdom. Their results indicated that 8% of the over 3000 respondents had neuropathic pain.
The largest of the studies, conducted by Bouhassira et al in France, found that 7% of 23,712 respondents to questionnaires randomly sent out to members of the French population had chronic pain with neuropathic characteristics.
Ohayon and colleagues telephonically interviewed a random sample of 3011 German adults (≥15 years) and determined that 7% suffered from chronic pain with neuropathic pain features.
A Canadian study, conducted by Toth et al, found a much higher prevalence of neuropathic pain in their telephone survey of 1207 randomly selected individuals from both urban and rural households in one Canadian province. In this study, telephonic use of the Douleur neuropathique en 4 questions (DN4) questionnaire identified neuropathic pain symptoms in 18% of the study population.
Elzahaf and colleagues had 104 telephone interview respondents from Derna City, Libya complete the Arabic S-LANSS questionnaire and identified 12% as have neuropathic pain.
Finally, Harifi et al conducted a telephone survey of 5328 members of the general Moroccan population and found, using the Moroccan validated version of the DN4 questionnaire, that 11% suffered from chronic pain with neuropathic characteristics.
References
Bouhassira D et al. Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 2008; 136(3):380-7.
de Moraes Vieira EB et al. Prevalence, characteristics, and factors associated with chronic pain with and without neuropathic characteristics in São Luís, Brazil. J Pain Symptom Manage 2012; 44(2):
Elzahaf RA et al. Translation and linguistic validation of the self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) scale for use in a Libyan population. Pain Pract 2013; 13(3):
Harifi G et al. Prevalence of chronic pain with neuropathic characteristics in the Moroccan general population: a national survey. Pain Med 2013; 14(2):
Ohayon MM, Stingl C. Prevalence and comorbidity of chronic pain in the German general population. Psychiatr Res 2012; 46(4):
Torrance N et al. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006; 7(4):281-9.
Toth C et al. The prevalence and impact of chronic pain with neuropathic pain symptoms in the general population.Pain Med 2009; 10(5):
Adapted from: Bouhassira D et al. Pain 2008; 136(3):380-7; de Moraes Vieira EB et al. J Pain Symptom Manage 2012; 44(2):239-51; Elzahaf RA et al. Pain Pract 2013; 13(3): ; Harifi G et al. Pain Med 2013; 14(2):287-92; Ohayon MM, Stingl C. Psychiatr Res 2012; 46(4):444-50; Torrance N et al. J Pain 2006;7(4):281-9; Toth C et al. Pain Med 2009; 10(5):918-29;

13. how do you overcome these challenges?
Discussion Question
what are some of your biggest challenges in diagnosing patients with neuropathic pain?
how do you overcome these challenges?
Speaker’s Notes
Ask the question shown on the slide to participants to stimulate discussion.

14. Diagnosing Neuropathic Pain Is Challenging
Diagnostic challenges
Multiple, complex mechanisms
Diverse symptoms
Difficulties in communicating and understanding symptoms
Recognition of comorbidities
Speaker’s Notes
This slide outlines the key challenges associated with diagnosing and managing neuropathic pain.
Part of the problem with recognizing neuropathic pain lies with the diversity of the symptomatology of the various pain syndromes and the multiplicity of the mechanisms that underlie them. The relationship between etiology, mechanisms and symptoms is complex; the same symptom in two patients may be caused by different mechanisms. Similarly, one mechanism could be responsible for many symptoms.
In addition, reaching a diagnosis may be hampered by difficulties in communication between patients and their doctors. Patients may find the symptoms they experience difficult to describe and physicians may not always be able to interpret the terminology patients use to describe their symptoms.
Comorbid conditions, such as anxiety and depression, are common and may further contribute to functional impairment and disability among patients with neuropathic pain. Comorbidities are often overlooked and need to be taken into account to achieve optimal management of patients with neuropathic pain.
The selection from available treatments may be sub-optimal. Inappropriate treatments are often used and this may, in part, be due to a lack of understanding of which treatments are most appropriate for neuropathic pain, and which analgesics confer little benefit. Because of the complexity of the relationship between mechanisms and symptoms, patients often respond differently to treatment of exactly the same pain syndrome. For example, two patients with postherpetic neuralgia may respond differently to the same treatment. This can confound diagnosis even further.
References
Harden N, Cohen M. Unmet needs in the management of neuropathic pain. J Pain Symptom Manage 2003; 25(5 Suppl):S12-7.
Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999; 353(9168):
Harden N, Cohen M. J Pain Symptom Manage 2003; 25(5 Suppl):S12-7; Woolf CJ, Mannion RJ. Lancet 1999; 353(9168):

15. The 3L Approach to Diagnosis1
Listen1,2
Patient verbal descriptors of pain, questions and answers
Speaker’s Notes
This slides describes the 3L (Listen, Locate and Look) approach to diagnosis.
The 3L approach will facilitate the assessment and successful diagnosis of neuropathic pain in the limited consultation time available in general practice. It involves the following steps:
Listen to patients’ verbal descriptors of their pain; ask appropriate questions and note their responses1,2
Locate the area of pain and/or determine the somatosensory nervous system lesion/dysfunction1,3
Look for sensory abnormalities and recognise their distribution pattern. Also look for abnormal behaviour or guarding of the affected area1,4
A differential diagnosis of neuropathic pain is dependent on the combined outcomes from the 3L approach.
References
Freynhagen R, Bennett MI. Diagnosis and management of neuropathic pain. BMJ 2009; 339:b3002.
Bennett MI et al. Using screening tools to identify neuropathic pain. Pain 2007; 127(3):
Freynhagen R et al. Pseudoradicular and radicular low-back pain – disease continuum rather than different entities? Answers from quantitative sensory testing. Pain 2008; 135(1-2):65-74.
Freynhagen R et al. The evaluation of neuropathic components in low back pain. Curr Pain Headache Rep 2009; 13(3):
Locate1,3
Look1,4
Somatosensory Nervous system lesion or disease
Sensory abnormalities in the painful area
1. Freynhagen R, Bennett MI. BMJ 2009; 339:b3002; 2. Bennett MI et al. Pain 2007; 127(3): ; 3. Freynhagen R et al. Pain 2008; 135(1-2):65-74; 4. Freynhagen R et al. Curr Pain Headache Rep 2009; 13(3):

16. Listen to the Patient Description of Pain
Question patients about their pain1
Be alert and ask for common verbal descriptors of neuropathic pain2
Use analogue or numerical scales to quantify the pain2
Use screening and assessment tools to distinguish neuropathic pain from non-neuropathic pain3
Speaker’s Notes
It is important for the clinician to ask the patient about their pain and listen carefully to the patient’s verbal descriptions of their pain, in addition to assessing the patient’s medical history for important diagnostic clues.
Use of a “cluster of terms” may signal neuropathic pain. The use of one or two typical verbal descriptors is highly suggestive of neuropathic pain, although not pathognomonic.
Screening tools can also be used to help distinguish neuropathic from non-neuropathic pain.
References
Cruccu G et al. EFNS guidelines on neuropathic pain assessment: revised Eur J Neurol 2010; 17(8):
Gilron I et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3):
Haanpää ML et al. Assessment of neuropathic pain in primary care. Am J Med 2009; 122(10 Suppl):S13-21; 4.
1. Haanpää ML et al. Am J Med 2009; 122(10 Suppl):S13-21; 2. Gilron I et al. CMAJ 2006; 175(3):265-75; 3. Cruccu G et al. Eur J Neurol 2010; 17(8):

17. Listen: Pain History in Neuropathic Pain
Identify the Following:
Areas of Further Exploration
Duration
Frequency
Quality
Intensity
Distribution and location of pain
Extent of interference with daily activity
Previous medical history
Exposure to toxins or other drug treatment (e.g., cancer chemotherapy, radiation)
Use of pain medications
Associated psychological and mood disturbance
Speaker’s Notes
The pain history should accompany a standard medical examination. The pain history should clarify pain location, distribution, intensity, quality and time course as well as the underlying disease and possibly the somatosensory nervous system lesion responsible for the pain.
In taking a full pain history, physicians should also explore any impact of the pain on sleep, daily functioning and emotional well-being. The possibility of the patient having psychiatric comorbidities such as anxiety and depression should also be explored.
Reference
Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003; 102(1-2):1-8.
Jensen TS, Baron R. Pain 2003; 102(1-2):1-8.

18. Listen: Neuropathic Signs and Symptoms Can Vary Widely
In One Individual
Between Individuals
Wide spectrum of signs and symptoms often co-exist at the same time
Signs and symptoms may vary within an individual over time
Signs and symptoms vary among individuals with the same underlying etiology
Signs and symptoms are shared across neuropathic pain states
Speaker’s Notes
Neuropathic pain is caused by multiple pathophysiologic mechanisms, which give rise to a wide variety of signs and symptoms. This slide focuses on the variability of those signs and symptoms, which can complicate diagnosis.
Signs and symptoms associated with neuropathic pain can play an important role in diagnosing the underlying condition and identifying the mechanisms causing the symptoms. Unfortunately, the symptoms associated with neuropathic pain vary considerably between patients with the same underlying condition and they can change over the course of the disease in the same individual.
This variability of symptoms between patients and etiologies can make recognition, diagnosis and treatment of neuropathic pain difficult.
References
Dworkin RH. An overview of neuropathic pain: syndromes, symptoms, signs, and several mechanisms. Clin J Pain 2002; 18(6):343-9.
Harden N, Cohen M. Unmet needs in the management of neuropathic pain. J Pain Symptom Manage 2003; 25(5 Suppl)S12-7.
Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003; 102(1-2):1-8.
Krause SJ, Bajckonja MM. Development of a neuropathic pain questionnaire. Clin J Pain 2003; 19(5):
Dworkin RH. Clin J Pain 2002; 18(6):343-9; Harden N, Cohen M. J Pain Symptom Manage 2003; 25(5 Suppl):S12-7); Jensen TS, Baron R. Pain 2003; 102(1-2):1-8; Krause SJ, Bajckonja MM. Clin J Pain 2003; 19(5):

19. Listen: Recognizing Neuropathic Pain
Be alert for common verbal descriptors of neuropathic pain:
Burning Tingling Shooting Electric shock-like Numbness
Speaker’s Notes
Verbal descriptors of pain can be important clues to the pathophysiologic mechanism behind the pain. For instance, with neuropathic pain, the pain is often described as burning, tingling or electric shock-like. Sensations of pins and needles or numbness are also frequently mentioned in conjunction with neuropathic pain conditions.
References
Baron R et al. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2010; 9(8):
Gilron I et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3):
Baron R et al. Lancet Neurol 2010; 9(8):807-19; Gilron I et al. CMAJ 2006; 175(3):

20. Listen: Sensory Symptoms of Neuropathic Pain
Lesion or disease of the somatosensory nervous system
Positive symptoms
(due to excessive neural activity)
Negative symptoms
(due to deficit of function)
Spontaneous pain
Hypoesthesia
Anesthesia
Allodynia
Hyperalgesia
Hypoalgesia
Speaker’s Notes
It is now recognized that neuropathic pain is “not a monolithic entity, but instead presents as a composite of pain and other sensory symptoms.” Each patient may have a combination of symptoms that may change over time (even within a single etiology).
Examples of positive symptoms are spontaneous pain, allodynia, hyperalgesia, dysesthesia and paresthesia. Examples of negative symptoms are hypoesthesia, anesthesia, hypoalgesia and analgesia.
References
Baron R et al. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol 2010; 9(8):
Jensen TS et al. The clinical picture of neuropathic pain. Eur J Pharmacol 2001; 429(1-3):1-11.
Dysesthesia
Analgesia
Paresthesia
Sensory abnormalities and pain paradoxically co-exist
Each patient may have a combination of symptoms
that may change over time (even within a single etiology)
Baron R et al. Lancet Neurol 2010; 9(8):807-19; Jensen TS et al. Eur J Pharmacol 2001; 429(1-3):1-11.

21. Listen: Positive Sensory Symptoms of Neuropathic Pain
Positive symptom
Definition
Typical verbal descriptors
Spontaneous pain
Painful sensations felt with no evident stimulus
Electric shock-like, burning
Allodynia
Pain due to a stimulus that does not normally provoke pain (e.g., touching, movement, cold, heat)
Vary with stimulus
Hyperalgesia
An increased response to a stimulus that is normally painful (e.g., cold, heat, pinprick)
Dysesthesia
An unpleasant abnormal sensation, whether spontaneous or evoked
Shooting, piercing, burning
Paresthesia
An abnormal sensation, whether spontaneous or evoked
Tingling, buzzing, vibrating
Speaker’s Notes
Spontaneous pain is the most frequent symptom in all painful neuropathies and presents with a burning quality, localized superficially, or electric shock-like pain for several seconds.
Allodynia is a painful response to a stimulus that is not normally painful.
Hyperalgesia is a heightened response to a stimulus that would normally evoke pain.
Dysesthesias are abnormal sensations that are unpleasant, and include shooting, lancinating (piercing/stabbing) or burning pains.
Paresthesias are abnormal sensations that are not unpleasant, such as tingling.
References
Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003; 102(1-2):1-8.
Merskey H, Bogduk N (eds). In: Classification of Chronic Pain. 2nd ed. IASP Press; Seattle, WA: 2011.
Adapted from: Jensen TS, Baron R. Pain 2003; 102(1-2):1-8; Merskey H, Bogduk N (eds). In: Classification of Chronic Pain. 2nd ed. IASP Press; Seattle, WA: 2011.

22. Listen: Negative Sensory Symptoms of Neuropathic Pain
Negative symptom
Definition
Typical verbal descriptor
Hypoesthesia
Diminished sensitivity to stimulation
Numbness
Anesthesia
Total loss of sensation (especially tactile sensitivity)
Hypoalgesia
Diminished pain in response to a normally painful stimulus
Analgesia
Absence of pain in response to stimulation that would normally be painful
Speaker’s Notes
Negative sensory symptoms of neuropathic pain, including hypoesthesia, anesthesia, hypoalgesia and analgesia, are typically described as a feeling of numbness by the patient.
References
Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003; 102(1-2):1-8.
Merskey H, Bogduk N (eds). In: Classification of Chronic Pain. 2nd ed. IASP Press; Seattle, WA: 2011.
Adapted from: Jensen TS, Baron R. Pain 2003; 102(1-2):1-8; Merskey H, Bogduk N (eds). In: Classification of Chronic Pain. 2nd ed. IASP Press; Seattle, WA: 2011.

23. Locate the Region of Pain
Correlate the region of pain to the lesion in the somatosensory nervous system*
Front
Back
Left
Right
Body maps are useful for the precise location of pain symptoms and sensory signs.
Body maps allow identification of the nerve damage.
Left
Right
Speaker’s Notes
In cases of neuropathic pain, body maps may be useful for the precise systematization of pain according to individual dermatomes.
It should be noted that in cases of referred pain, the location of the pain and of the injury or nerve lesion/dysfunction may not be correlated.
References
Gilron I et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3):
Soler MD et al. Referred sensations and neuropathic pain following spinal cord injury. Pain 2010; 150(1):192-8.
Walk D et al. Quantitative sensory testing and mapping: a review of nonautomated quantitative methods for examination of the patient with neuropathic pain. Clin J Pain 2009; 25(7):
*Note that in cases of referred neuropathic pain, as can occur for example in some cases of spinal cord injury, the location of the pain and of the lesion/dysfunction may not be correlated
Gilron I et al. CMAJ 2006; 175(3):265-75; Soler MD et al. Pain 2010; 150(1):192-8; Walk D et al. Clin J Pain 2009; 25(7):

24. Look for Sensory and/or Physical Abnormalities
Inspect the painful body area and compare it with the corresponding healthy area1,2
Conduct simple bedside tests to confirm sensory abnormalities1-4
Speaker’s Notes
Bedside examination of patients with suspected neuropathic pain is aimed at identifying altered sensation in the painful area, and so responses should be compared with a non-painful or adjacent area. A painful response to lightly stroking the skin with a finger or cotton wool is a sign of allodynia, a common characteristic of neuropathic pain. Numbness (hypoalgesia) or an exaggerated painful response (hyperalgesia) to pinprick testing with a monofilament or sharp object confirms an altered pinprick threshold. Inability to distinguish warm from cold objects suggests an altered thermal threshold.
A combination of characteristic painful symptoms in an area of altered sensation on bedside testing is usually enough to make a diagnosis of neuropathic pain. Neither imaging nor electromyography are generally considered necessary and, in fact, electromyography may be useless in cases of diabetic peripheral neuropathy.
References
Baron R, Tölle TR. Assessment and diagnosis of neuropathic pain. Curr Opin Support Palliat Care 2008; 2(1):1-8.
Freynhagen R, Bennett MI. Diagnosis and management of neuropathic pain. BMJ 2009; 339:b3002.
Gilron I et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3):
Haanpää ML et al. Assessment of neuropathic pain in primary care. Am J Med 2009; 122(10 Suppl):S13-21.
1. Baron R, Tölle TR. Curr Opin Support Palliat Care 2008; 2(1):1-8; 2. Freynhagen R, Bennett MI. BMJ 2009; 339:b3002;
3. Haanpää ML et al. Am J Med 2009; 122(10 Suppl):S13-21; 4. Gilron I et al. CMAJ 2006; 175(3):

25. what bedside tests do you typically use in your practice?
Discussion Question
what bedside tests do you typically use in your practice?
why?
Speaker’s Notes
Ask the question shown on the slide to participants to stimulate discussion.

26. Look: Simple Bedside Tests
Stroke skin with brush,
cotton or apply acetone
Sharp, burning
superficial pain
ALLODYNIA
Light manual pinprick with
safety pin or sharp stick
Very sharp,
superficial pain
Speaker’s Notes
This slide describes several simple assessments, that can readily be employed in the physician’s office, for allodynia (pain due to a stimulus that does not normally provoke pain) and hyperalgesia (increased pain from a stimulus that normally provokes pain). In each case, the control would be the identical stimulus applied to the unaffected contralateral side.
Mechanical allodynia can be assessed by stroking the skin with a brush, gauze, or cotton. Patients with mechanical allodynia might complain that the brushing of fabric such as a shirt over their skin is painful and that they avoid being touched by others, wear shoes or even socks.
Cold allodynia may be tested by applying acetone to the skin.
Mechanical hyperalgesia can be evaluated by using a safety pin or sharp stick to the skin. Patients with pinprick hyperalgesia may complain of very increased painful sensation with this evoked nociceptive stimuli.
References
Baron R. Peripheral neuropathic pain: from mechanisms to symptoms. Clin J Pain 2000; 16(2 Suppl):S12-20.
Jensen TS, Baron R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain 2003; 102(1-2):1-8.
HYPERALGESIA
Baron R. Clin J Pain 2000; 16(2 Suppl):S12-20; Jensen TS, Baron R. Pain 2003; 102(1-2):1-8.

27. Discussion Question
do you use a screening tool for neuropathic pain in your practice? if so, which tool and why?
Speaker’s Notes
Ask the question shown on the slide to participants to stimulate discussion.

28. Neuropathic Pain Screening Tools
LANSS
DN4
NPQ
painDETECT
ID Pain
Symptoms
Pricking, tingling, pins and needles x X
Electric shocks of shooting
Hot or burning
Numbness
Pain evoked by light touching
Painful cold or freezing pain
Clinical examination
Brush allodynia
Raised soft touch threshold
Altered pin prick threshold }
Neuropathic pain screening tools rely largely on common verbal descriptors of pain
Select tool(s) based on ease of use and validation in the local language
Speaker’s Notes
This slide summarizes the screening tools currently used for neuropathic pain.
Screening methods for neuropathic pain consist mostly of characteristic verbal descriptors, though some have simple bedside examinations in addition. Examples of the latter are the LANSS pain scale and the DN4 questionnaire, which have an approximate accuracy of 80% (for LANSS) and 90% (for ND4), compared with expert clinical judgment in identifying patients with neuropathic pain. Screening methods, however, are not a substitute for good clinical assessment and are not intended to be diagnostic methods.
References
Bennett MI et al. Using screening tools to identify neuropathic pain. Pain 2007; 127(3):
Haanpää M et al. NeuPSIG guidelines on neuropathic pain assessment. Pain 2011; 152(1):14-27. }
Some screening tools also include bedside neurological examination
DN4 = Douleur Neuropathique en 4 Questions (DN4) questionnaire; LANSS = Leeds Assessment of Neuropathic Symptoms and Signs; NPQ = Neuropathic Pain Questionnaire
Bennett MI et al. Pain 2007; 127(3): ; Haanpää M et al. Pain 2011; 152(1):14-27.

29. Sensitivity and Specificity of Neuropathic Pain Screening Tools
Name
Description
Sensitivity*
Specificity*
Interview-based
NPQ
10 sensory-related items + 2 affect items
66%
74%
ID-Pain
5 sensory items + 1 pain location NR
painDETECT
7 sensory items + 2 spatial characteristics items
85%
80%
Interview + physical tests
LANSS
5 symptom items + 2 clinical exam items
82–91%
80–94%
DN4
7 symptom items + 3 clinical exam items
83%
90%
Speaker’s Notes
This slide summarizes the screening tools currently used for neuropathic pain, providing the sensitivity and specificity for each, when available.
Reference
Bennett MI et al. Using screening tools to identify neuropathic pain. Pain 2007; 127(3):
Tests incorporating both interview questions and physical tests have higher sensitivity and specificity than tools that rely only on interview questions
*Compared with clinical diagnosis
DN4 = Douleur neuropathic en 4 questions; LANSS = Leeds Assessment of Neuropathic Symptoms and Signs; NPQ = Neuropathic Pain Questionnaire; NR = not reported
Bennett MI et al. Pain 2007; 127(3):

30. LANSS Scale Completed by physician in office
Differentiates neuropathic from nociceptive pain
5 pain questions and 2 skin sensitivity tests
Identifies contribution of neuropathic mechanisms to pain
Validated
Speaker’s Notes
This slide shows the LANSS scale, which was developed to distinguish neuropathic symptoms and signs from those arising through nociceptive pain.
The LANSS scale is based on an analysis of sensory description and examination of sensory dysfunction, and provides immediate information in the clinical setting.
Patients are given five descriptions of different types of pain and are asked whether each description matches the pain they have experienced over the previous week. Skin sensitivity is assessed by comparing the painful area with a contralateral or adjacent non-painful area for the presence of allodynia and an altered pinprick threshold.
A maximum total score of 24 can be achieved. If the patient scores less than 12, neuropathic mechanisms are unlikely to be contributing to their pain; if the patient scores 12 or more, neuropathic mechanisms are likely to be contributing to their pain.
The scale can distinguish patients with neuropathic pain from those with nociceptive pain, and may help to individualize treatment according to specific pain mechanisms. The scale has been validated and may have utility as a diagnostic tool in both clinical practice and in clinical trials.
Reference
Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain 2001; 92(1-2):
LANSS = Leeds Assessment of Neuropathic Symptoms and Signs
Bennett M. Pain 2001; 92(1-2):

31. DN4 Completed by physician in office
Differentiates neuropathic from nociceptive pain
2 pain questions (7 items)
2 skin sensitivity tests (3 items)
Score 4 is an indicator for neuropathic pain
Validated
Speaker’s Notes
This slide shows the DN4 diagnostic questionnaire, which was developed by The French Neuropathic Pain Group to differentiate neuropathic pain from non-neuropathic pain.
The DN4 scale is based on an analysis of sensory description and examination of sensory dysfunction, and provides immediate information in the clinical setting.
Patients are given seven descriptions of different types of pain or pain-related symptoms and are asked whether their pain is associated with the characteristic or symptom described (yes/no). The presence of touch hypoesthesia, pricking hypoesthesia and brushing pain is noted (yes/no).
The scale has been validated and may have utility as a diagnostic tool in both clinical practice and in clinical trials.
Reference
Bouhassira D et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 2005; 114(1-2):29-36.
DN4 = Douleur neuropathique en 4 questions Bouhassira D et al. Pain 2005; 114(1-2):29-36.

32. Clinical Approach to Suspected Neuropathic Pain
Are verbal descriptors and history suggestive of neuropathic pain?1
Whenever possible, treat the underlying cause/disease
Yes No
Can you detect sensory abnormalities using simple bedside tests?1,2
Yes No
Can you identify the
responsible somatosensory nervous
system lesion/disease2
Probable nociceptive pain
Yes No
Speaker’s Notes
Confirming the presence of neuropathic pain involves:
Identification of a cluster of common verbal descriptors and history leading to the suspicion of neuropathic pain
Finding sensory abnormalities (either a deficit, such as hypoesthesia, or an excess of function, such as allodynia, hyperalgesia) in the painful area adding support for a neuropathic origin of the pain, particularly if the pain and the sensory abnormality are within a neuroanatomical territory
Identification of the responsible neurological lesion/disease
If a neuropathic pain syndrome is diagnosed, the underlying cause should be treated and appropriate analgesic therapy should be initiated.
Occasionally sensory abnormalities may not be detected and/or the nervous system lesion/disease cannot be easily identified. If neuropathic pain is still suspected, specialist referral should be considered (and appropriate pain treatment initiated in the interim period).
References
Freynhagen R, Bennett MI. Diagnosis and management of neuropathic pain. BMJ 2009; 339:b3002.
Haanpää ML et al. Assessment of neuropathic pain in primary care. Am J Med 2009; 122(10 Suppl):S13-21.
Treede RD et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008; 70(18):
Consider specialist referral and if neuropathic pain is still suspected, consider treatment in the interim period3
Neuropathic pain is likely:
initiate treatment3
1. Freynhagen R, Bennett MI. BMJ 2009; 339:b3002; 2. Haanpää ML et al. Am J Med 2009; 122(10 Suppl):S13-21; 3. Treede RD et al. Neurology 2008; 70(18): 32

33. how has neuropathic pain affected some of your patients?
Discussion Question
how has neuropathic pain affected some of your patients?
Speaker’s Notes
Ask the question shown on the slide to participants to stimulate discussion.

34. Patient-Reported Burden of Neuropathic Pain Is Significant
Activities of daily living
Psychological burden
Physical burden
Neuropathic pain
Reduced quality of life
Sleep disturbances
Drowsiness when awake
Depression
Psychological distress
Difficulty in concentration
Physical disability
Speaker’s Notes
As indicated on this slide, patients with neuropathic pain report significant deficits in numerous health and quality of life measures, including sleep, mood, anxiety and physical disability.
References
Cruz-Almeida Y et al. Chronicity of pain associated with spinal cord injury: a longitudinal analysis. J Rehab Res Dev 2005; 42(5):
Gilron I et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3):
Jensen MP et al. The impact of neuropathic pain on health-related quality of life: review and implications. Neurology 2007; 68(15):
Khenioui H et al. Évaluation fonctionnelle de la douleur chronique chez le patient blessé médullaire. Ann Readapt Med Phys 2006; 49(3):
Meyer-Rosberg K et al. Peripheral neuropathic pain – a multidimensional burden for patients. Eur J Pain 2001; 5(4):
Both the intensity of the pain and the duration of the condition exacerbate the patient’s burden
Cruz-Almeida Y et al. J Rehab Res Dev 2005; 42(5):585-94; Gilron I et al. CMAJ 2006; 175(3):265-75; Jensen MP et al. Neurology 2007; 68(15): ; Khenioui H et al. Ann Readapt Med Phys 2006; 49(3):125-37; Meyer-Rosberg K et al. Eur J Pain 2001; 5(4):

35. Chronic Neuropathic Pain Has a Significant Impact on Daily Functioning* *
Pain interference * *
*p <0.001 * * *
Speaker’s Notes
This slide shows data from a cross-sectional United Kingdom study involving primary care patients with chronic, predominantly neuropathic pain (n = 241), chronic non-neuropathic pain (n = 1179) and no chronic pain (n = 1537). Chronic, predominantly neuropathic pain was identified using the self-completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) questionnaire, which is a seven-item questionnaire that yields a maximum score of 24, with scores of 12 or more having positive predictive value for neuropathic pain (selected as the cut-off for this study). The current severity of chronic pain was assessed on a numerical rating scale from 0 = no pain to 10 = pain as severe as it could be. The quality and severity of pain and its interference with daily function were assessed using the Neuropathic Pain Scale (NPS) and the Brief Pain Inventory (BPI), respectively. The S-LANSS questionnaire, pain severity numerical rating scale, NPS and BPI were only completed by those responding positively to two chronic pain case identification questions. The Short Form (36) Health Survey questionnaire (SF-36) was used to assess patients’ ratings of their own health status.
The BPI results shown here demonstrate that patients with neuropathic pain have more severe pain and greater disability across all the daily functions and activities assessed by the scale than those with non-neuropathic pain.
Chronic neuropathic pain was associated with statistically significantly (p ≤0.001) greater interference with sleep, general activity, normal work, mood, walking ability, relationships, and enjoyment of life.
Reference
Smith BH et al. Health and quality of life associated with chronic pain of predominantly neuropathic origin in the community. Clin J Pain 2007; 23(2):143-9. *
BPI = Brief Pain Inventory, which scores extent pain interferes with activities in last 24 hours from 0 (does not interfere) to 10 (completely interferes)
Adapted from: Smith BH et al. Clin J Pain 2007; 23(2):143-9.

36. Patients with Peripheral Neuropathic Pain Experience Significant Comorbid Symptoms
Pain interference
Speaker’s Notes
This study was undertaken to assess the health-related quality of life and burden of illness due to pain and its treatment in 126 patients with neuropathic pain due to a peripheral nerve or root lesion. Patients were recruited from two multidisciplinary pain clinics in Sweden. Patients were asked to rate the extent to which they were bothered by 25 pain-related symptoms and/or side-effects of drug treatment during the previous week (rated as 1 = no discomfort to 7 = very severe discomfort). This slide shows the proportions of patients who rated their discomfort as 4 (moderate) to 7 (very severe). Data on seven of the 10 most frequently reported comorbid symptoms are shown on the slide.
Overall, 88% of patients reported some degree of discomfort associated with their pain or its treatment. Difficulty sleeping was the most bothersome symptom and was moderate to very severe in 60% of patients. A lack of energy, drowsiness and difficulty in concentrating, were also troubling for many individuals. Moderate to very severe levels of depression were reported by 35% (one in three patients), and anxiety by 27% (one in four patients). These data indicate that sleep disturbance, anxiety and depression and related symptoms are prevalent among patients with peripheral neuropathic pain.
In terms of other comorbidities, it should also be noted that diabetic peripheral neuropathy is frequently associated with autonomic diabetic neuropathy, with its associated problematic “vegetative” symptoms and increased risk of mortality.
References
Meyer-Rosberg K et al. Peripheral neuropathic pain – a multidimensional burden for patients. Eur J Pain 2001; 5(4):
Vinik AI et al. Diabetic autonomic neuropathy. Diabetes Care 2003; 26(5):
Meyer-Rosberg K et al. Eur J Pain 2001; 5(4):379-89; Vinik AI et al. Diabetes Care 2003; 26(5):

37. Neuropathic Pain Is Associated with Sleep Disturbance, Anxiety and Depression
Functional impairment
Speaker’s Notes
Patients who suffer from chronic neuropathic pain experience difficulties initiating and maintaining sleep and are often depressed and anxious. The inter-relationship between these three factors, as shown on this slide, is complex, but must be considered carefully if treatment for neuropathic pain is to be satisfactory.
Although most pain disorders begin with injury or disease, their course and outcome are affected by emotional, behavioral and social factors. An individual’s emotional reaction to and capacity to cope with the fluctuating course of neuropathic pain disorders and their complications such as physical impairment, disability, and loss of role functioning will also affect outcome.
Chronic pain significantly interferes with sleep, with most studies showing a positive correlation between pain intensity and degree of sleep disturbance. Many chronic pain patients also have signs and symptoms of depression and anxiety; sleep deprivation can lead to anxiety, and depression can be both the cause and result of sleep deprivation.
Chronic pain, sleep disturbances, and depression/anxiety must be addressed if patients are to be restored to optimal functionality. Physicians must evaluate all aspects of pain, sleep and mood in patients with chronic pain.
Management and treatment should address both the pain and the comorbidities, to improve daily functioning and enhance quality of life.
Reference
Nicholson B, Verma S. Comorbidities in chronic neuropathic pain. Pain Med 2004; 5(Suppl 1):S9-27.
Anxiety and
depression
Sleep
disturbances
Nicholson B, Verma S. Pain Med 2004; 5(Suppl 1):S9-27.

38. Management of Neuropathic Pain
Diagnosis
Treatment of underlying conditions
Pharmacological and non-pharmacological treatment of neuropathic pain
Treatment of comorbidities
Improved physical functioning
Improved sleep quality
Reduced pain
Improved psychological state
Speaker’s Notes
Once diagnosed, successful management of neuropathic pain encompasses much more than pain relief. Clinicians need to consider a holistic approach to the treatment of the underlying condition and comorbid conditions – the improvement of patients’ overall quality of life, physical functioning and sleep quality, along with a reduction in the psychological distress associated with neuropathic pain conditions.
References
Haanpää ML et al. Assessment of neuropathic pain in primary care. Am J Med 2009; 122(10 Suppl):S13-21.
Horowitz SH. Recent clinical advances in diabetic polyneuropathy. Curr Opin Anaesthesiol 2006; 19(5):573-8.
Johnson L. The nursing role in recognizing and assessing neuropathic pain. Br J Nurs 2004; 13(18):
Meyer-Rosberg K et al. Peripheral neuropathic pain – a multidimensional burden for patients. Eur J Pain 2001; 5(4):
Nicholson B, Verma S. Comorbidities in chronic neuropathic pain. Pain Med 2004; 5(Suppl 1):S9-27.
Improved overall quality of life
The earlier a diagnosis is made, the more opportunities there are to improve patient outcomes
Haanpää ML et al. Am J Med 2009; 122(10 Suppl):S13-21; Horowitz SH. Curr Opin Anaesthesiol 2006; 19(5):573-8; Johnson L. Br J Nurs 2004; 13(18):1092-7;
Meyer-Rosberg K et al. Eur J Pain 2001; 5(4):379-89; Nicholson B et al. Pain Med 2004; 5(Suppl 1):S9-27. 38

39. Goals in the Treatment of Neuropathic Pain
2o goals
Restoration or improvement in:
1o goal:
>50% pain relief*
… but be realistic!
Sleep
Mood
Speaker’s Notes
It is important to discuss and agree on realistic treatment goals before starting a treatment plan. Total pain relief is usually an unrealistic goal and will result in frustration for both patient and doctor. A reduction in pain of about 30–50% is more realistic, and is clinically important to patients. With this in mind, patients need to accept reduced pain and improved function with minimum acceptable side effects as a goal of pain management.
References
Argoff CE et al. Consensus guidelines: treatment planning and options. Diabetic peripheral neuropathic pain. Mayo Clin Proc 2006; 81(Suppl 4):S12-25.
Lindsay TJ et al. Treating diabetic peripheral neuropathic pain. Am Fam Physician 2010; 82(2):151-8.
Quality of life
Function
*Note: pain reduction of 30–50% can be expected with maximal doses in most patients
Argoff CE et al. Mayo Clin Proc 2006; 81(Suppl 4):S12-25; Lindsay TJ et al. Am Fam Physician 2010; 82(2):151-8.

40. Multimodal Treatment of Neuropathic Pain
Lifestyle management
Sleep hygiene
Stress management
Pharmacotherapy
Interventional
procedures
Physical or
occupational therapy
Speaker’s Notes
The 2011 Institute of Medicine (IOM) pain report suggested that a mind-body approach should be used when caring for patients with pain.
The biopsychosocial approach, combining physical and emotional factors in assessing and treating chronic pain, offers a uniquely valuable clinical perspective. This mind-body perspective is now generally accepted by pain researchers and has been found useful by clinicians in various disciplines.
This animated slide lists components that might be included in such a multimodal approach to pain therapy.
References
Gatchel RJ et al. The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull 2007; 133(4):
Institute of Medicine. Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research.; National Academies Press; Washington, DC: 2011.
Mayo Foundation for Medical Education and Research. Comprehensive Pain Rehabilitation Center Program Guide. Mayo Clinic; Rochester, MN: 2006.
Education
Complementary therapies
Biofeedback
Mayo Foundation for Medical Education and Research. Comprehensive Pain Rehabilitation Center Program Guide. Mayo Clinic; Rochester, MN: 2006.

41. Multimodal pain management
Various Non-pharmacological Treatments Are Available for Neuropathic Pain1-6
Physiotherapy1
Psychotherapy/CBT6,7
Various non-pharmacological treatment modalities are mentioned in guidelines, but no modality is universally recommended1-5
Multimodal pain management
programs5,6
Patient education1
Alternative therapies and spiritual healing1-4
Speaker’s Notes
Various non-pharmacological treatments are available for neuropathic pain. These include communication strategies, such as patient education; physical modalities, such as physiotherapy; psychological modalities, such as cognitive behavioral therapy; and a wide variety of alternative spiritual and religious-based treatments, such as meditation and hijama cupping therapy.
In general non-pharmacological treatment is complementary to drug therapy and, given their presumed safety, non-pharmacologic treatments should be considered whenever appropriate.
References
Bril V et al. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011; 76(20):
Chetty S et al. Clinical practice guidelines for management of neuropathic pain: expert panel recommendations for South Africa. S Afr Med J 2012; 102(5):
Cruccu G et al. EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 2007; 14(9):
Dubinsky RM et al. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2004; 63(6):
Freynhagen R, Bennett MI. Diagnosis and management of neuropathic pain. BMJ 2009; 339:b3002.
Morley S. Efficacy and effectiveness of cognitive behaviour therapy for chronic pain: progress and some challenges. Pain 2011;152(3 Suppl):S
Pittler MH, Ernst E. Complementary therapies for neuropathic and neuralgic pain: systematic review. Clin J Pain 2008; 24(8):
CBT = cognitive behavioral therapy
1. Chetty S et al. S Afr Med J 2012; 102(5):312-25; 2. Bril V et al. Neurology 2011; 76(20): ; 3. Cruccu G et al. Eur J Neurol 2007; 14(9):952-70; 4. Pittler MH, Ernst E. Clin J Pain 2008; 24(8):731-35; 5. Dubinsky RM et al. Neurology 2004; 63(6):959-65; 6. Freynhagen R, Bennett MI. BMJ 2009; 339:b3002; 7. Morley S. Pain 2011;152(3 Suppl):S

42. Discussion Question
what non-pharmacological approaches to neuropathic pain management have you found helpful for your patients?
Speaker’s Notes
Ask the question shown on the slide to participants to stimulate discussion.

43. Evidence for Non-pharmacological Therapies in Neuropathic Pain
Studied therapies include:
Acupuncture
Electrostimulation
Herbal medicine
Magnets
Dietary supplements
Imagery
Spiritual healing
Limited evidence for most modalities
Evidence is encouraging and warrants further study for:
Cannabis extract
Carnitine
Electrostimulation
Magnets
The effectiveness of B vitamins in reducing chronic neuropathic pain has not been established
Speaker’s Notes
Although many patients with neuropathic pain pursue complementary and alternative treatments, rigorous evidence supporting efficacy of non-drug therapy is limited.
This slide is based on the results of a systematic review of the use of complementary therapies in the treatment of neuropathic pain. Following a systematic search of numerous databases, 15 trials and five systematic review/meta-analyses were identified. Evaluation of these publications revealed there is limited evidence for most non-pharmacological therapies in neuropathic pain. However, further investigation may be warranted to study the effectiveness of cannabis extract, carnitine, electrostimulation and magnets.
Additionally, a Cochrane review found there was insufficient evidence to establish the effectiveness of vitamin B in reducing neuropathic pain due to peripheral neuropathy.
References
Ang CD et al. Vitamin B for treating peripheral neuropathy. Cochrane Database Syst Rev 2008; 3:CD
Pittler MH, Ernst E. Complementary therapies for neuropathic and neuralgic pain: systematic review. Clin J Pain 2008; 24(8):
Ang CD et al. Cochrane Database Syst Rev 2008; 3:CD004573; Pittler MH, Ernst E. Clin J Pain 2008; 24(8):

44. IASP NeuPSIG Recommendations: Interventional Management of Neuropathic Pain
Weakly Recommended
Epidural or paravertebral nerve block(s) for herpes zoster
Epidural steroid injection(s) for radiculopathy
Spinal cord stimulation for failed back surgery syndrome with radiculopathy and complex regional pain syndrome 1
Not recommended
Sympathetic nerve blocks for postherpetic neuralgia
Radiofrequency lesioning for lumbar radiculopathy
Speaker’s Notes
As neuropathic pain can be frequently unresponsive to pharmacologic and non- interventional management strategies, the IASP NeuPSIG conducted a systematic review of the literature on the interventional management of neuropathic pain.
For most interventions, the quality of evidence was so low as to be inconclusive and no recommendations could be made. The quality of evidence was moderate for the interventions recommended for and against on this slide.
Reference
Dworkin RH et al. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain 2013; 154(11):
IASP = International Association for the Study of Pain; NeuPSIG = Neuropathic Pain Special Interest Group
Dworkin RH et al. Pain 2013; 154(11):

45. Mechanism-Based Pharmacological Treatment of Neuropathic Pain
Nerve lesion/disease
Central sensitization
Brain
Medications affecting peripheral sensitization:
Capsaicin
Local anesthetics
TCAs
Medications affecting descending modulation:
SNRIs
TCAs
Tramadol, opioids
Medications affecting central sensitization:
α2δ ligands
TCAs
Tramadol, opioids
Descending
modulation
Ectopic discharge
Nerve lesion/disease
Speaker’s Notes
This slide outlines some treatment options for neuropathic pain, indicating where in the pain pathway these agents take effect.
Pain arising as a direct consequence of a lesion or disease affecting the somatosensory system is defined as “neuropathic pain”.
Peripheral mechanisms of neuropathic pain include membrane hyperexcitability in the nociceptive neurons and ectopic discharges along sensory nerves, which may lead to transcriptional changes in the dorsal root ganglia (peripheral sensitization). Peripheral mechanisms can trigger changes within the central nervous system(central mechanisms) as well.
Central mechanisms in the spinal cord include increased excitability in the dorsal horn neurons, sprouting of non- nociceptive myelinated A-beta-afferents in the dorsal horn that form new connections with the nociceptive neurons in the laminae I and II, and loss of inhibitory controls (disinhibition). Central mechanisms in the supraspinal systems include hyperexcitability and changes in synaptic activity and reorganization within the brainstem nuclei, thalamus and the brain cortex associated with pain matrix (central sensitization).
References
Attal N et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010; 17(9):1113-e88.
Beydoun A, Backonja MM. Mechanistic stratification of antineuralgic agents. J Pain Symptom Manage 2003; 25(5 Suppl):S18-30.
Jarvis MF, Boyce-Rustay JM. Neuropathic pain: models and mechanisms. Curr Pharm Des 2009; 15(15):
Gilron I et al. Neuropathic pain: a practical guide for the clinician. CMAJ 2006; 175(3):
Moisset X, Bouhassira D. Brain imaging of neuropathic pain. NeuroImage 2007; 37(Suppl 1):S80-8.
Morlion B. Pharmacotherapy of low back pain: targeting nociceptive and neuropathic pain components. Curr Med Res Opin 2011; 27(1):11-33.
Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002; 5(Suppl):
Nerve lesion/disease
Peripheral sensitization
Central sensitization
Nociceptive afferent fiber
Spinal cord
SNRI = serotonin-norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant
Adapted from: Attal N et al. Eur J Neurol 2010; 17(9):1113-e88; Beydoun A, Backonja MM. J Pain Symptom Manage 2003; 25(5 Suppl):S18-30; Jarvis MF, Boyce-Rustay JM. Curr Pharm Des 2009; 15(15):1711-6; Gilron I et al. CMAJ 2006; 175(3):265-75; Moisset X, Bouhassira D. NeuroImage 2007; 37(Suppl 1):S80-8; Morlion B. Curr Med Res Opin 2011; 27(1):11-33; Scholz J, Woolf CJ. Nat Neurosci 2002; 5(Suppl): 45

46. Role of a2d-Linked Calcium Channels in Neuropathic Pain
Binding of α2δ ligands to
α2δ inhibits calcium channel transport
Calcium channels transported to nerve terminals in dorsal horn X X X
Increased numbers
of calcium channels
Increased
calcium influx X
Injury stimulates
production of calcium channel
Speaker’s Notes
One of the mechanisms by which pain sensitivity is increased in neuropathic pain involves an increase in the production of the α2δ subunit of calcium channels. This results in the transportation of greater numbers of calcium channels to the nerve terminals in the dorsal horn, and a subsequent increase in neuronal excitability.
Recent studies suggest α2δ ligands counter this effect by modulating calcium channel trafficking through binding to the α2δ subunit of calcium channels and inhibiting calcium channel transport.
Reference
Bauer CS et al. The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. J Neurosci 2009; 29(13): X
Increased neuronal
excitability
INCREASED PAIN SENSITIVITY X
Nerve injury
Note: gabapentin and pregabalin are α2δ ligands
Bauer CS et al. J Neurosci 2009; 29(13):

47. Adverse Effects of a2d Ligands
System
Adverse effects
Digestive system
Dry mouth
CNS
Dizziness, somnolence
Other
Asthenia, headache, peripheral edema, weight gain
Speaker’s Notes
The most common adverse effects experienced with α2δ ligands such as gabapentin and pregabalin are dry mouth, dizziness, headache, weight gain, peripheral edema, asthenia and somnolence.
Reference
Attal N, Finnerup NB. Pharmacological management of neuropathic pain. Pain Clinical Updates 2010; 18(9):1-8.
α2δ ligands include gabapentin and pregabalin
CNS = central nervous system
Attal N, Finnerup NB. Pain Clinical Updates 2010; 18(9):1-8.

48. How Antidepressants Modulate Pain
Brain
Inhibiting reuptake of serotonin and norepinephrine enhances descending modulation
Perception
Ascending input
Descending modulation
Ectopic discharge
Nerve lesion
Speaker’s Notes
The main analgesic effect of antidepressants is thought to occur by increasing the amounts of serotonin and noradrenaline available in the synaptic clefts at the spinal and supraspinal levels, and thereby enhancing the inhibitory effects of the descending modulatory pathways.
It is interesting to note that at therapeutic concentrations, antidepressants have very little analgesic effect on nociception, suggesting they may help “normalize” the function of an altered pain system rather than inhibiting pain transmission.
Reference
Verdu B et al. Antidepressants for the treatment of chronic pain. Drugs 2008; 68(18):
Transmission
Glial cell activation
Nociceptive afferent fiber
Spinal cord
Verdu B et al. Drugs 2008; 68(18):

49. Adverse Effects of Antidepressants
System
TCAs
SNRIs
Digestive system
Constipation, dry mouth, urinary retention
Constipation, diarrhea, dry mouth, nausea, reduced appetite
CNS
Cognitive disorders, dizziness, drowsiness, sedation
Dizziness, somnolence
Cardiovascular
Orthostatic hypotension, palpitations
Hypertension
Other
Blurred vision, falls, gait disturbance, sweating
Elevated liver enzymes, elevated plasma glucose, sweating
Speaker’s Notes
The most common adverse effects of TCAs include dry mouth, constipation, urinary retention, sweating, dizziness, blurred vision, palpitation, orthostatic hypotension, drowsiness and sedation. Other adverse effects include cognitive disorders, confusion, gait disturbance and falls, particularly in the elderly.
The most frequently experienced adverse with SNRIs include dry mouth, constipation, diarrhea, nausea, reduced appetite, sweating, dizziness and somnolence. Rare adverse effects include elevated liver enzymes, plasma glucose levels and blood pressure.
Reference
Attal N, Finnerup NB. Pharmacological management of neuropathic pain. Pain Clinical Updates 2010; 18(9):1-8.
CNS = central nervous system; TCA = tricyclic antidepressant; SNRI = serotonin-norepinephrine reuptake inhibitor
Attal N, Finnerup NB. Pain Clinical Updates 2010; 18(9):1-8.

50. Pharmacological Management of Neuropathic Pain
Initiate treatment with one or more first-line treatments:
α2δ ligands (gabapentin, pregabalin)
SNRIs (duloxetine, venlafaxine)
STEP 1
TCAs* (nortriptyline, desipramine)
Topical lidocaine (for localized peripheral pain)
If there is partial pain relief, add another first-line medication
If there is no or inadequate pain relief, switch to another first-line medication
STEP 2
Speaker’s Notes
This slide presents the 2010 International Association for the Study of Pain (IASP) recommendations for the pharmacological management of neuropathic pain.
Based on these recommendations, first-line therapies include gabapentin, pregabalin, duloxetine, venlafaxine, nortriptyline and desipramine, as well as topical lidocaine for localized peripheral neuropathic pain. In addition, opioid analgesics and tramadol may be used first-line (alone or in combination) in patients with severe neuropathic pain, neuropathic cancer pain, episodic exacerbations of severe pain, and when prompt relief duration titration of first-line medication is required.
If there is partial, inadequate or no pain relief obtained with the first-line medication selected, the guidelines recommend either adding or switching to another first-line medication. It is only when first-line medication, alone and in combination fail, that second- and third-line medications should be used. Referral to a pain specialist should also be considered at this point.
References
Dworkin RH et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010; 85(3 Suppl):S3-14.
Freynhagen R, Bennett MI. Diagnosis and management of neuropathic pain. BMJ 2009; 339:b3002.
If first-line medications alone and in combination fail, consider second-line medications (opioids, tramadol) or third-line medications (bupropion, citalopram, paroxetine, carbamazepine, lamotrigine, oxcarbazepine, topiramate, valproic acid, topical capsaicin, dextromethorphan, memantine, mexiletine) or referral to pain specialist
STEP 3
*Use tertiary amine TCAs such as amitiptyline only if secondary amine TCAs are unavailable
Note: there is insufficient support for the use of nsNSAIDs in neuropathic pain
nsNSAID = non-specific non-steroidal anti-inflammatory drug; SNRI = serotonin-norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant
Dworkin RH et al. Mayo Clin Proc 2010 ; 85(3 Suppl):S3-14; Freynhagen R, Bennett MI. BMJ 2009; 339:b3002.

51. Prescribing Recommendations for First-Line Medications
Starting dose
Titration
Max. dosage
Trial duration
α2δ ligands
Gabapentin
100–300 mg at bedtime or tid
↑ by 100–300 mg tid every 1–7 days
3600 mg/day
3–8 weeks + 2 weeks at max. dose
Pregabalin
50 mg tid or 75 mg bid
↑ to 300 mg/day after 3–7 days, then by 150 mg/day every 3–7 days
600 mg/day
4 weeks
SNRIs
Duloxetine
30 mg qd
↑ to 60 mg qd after 1 week
60 mg bid
Venlafaxine
37.5 mg qd
↑ by 75 mg each week
225 mg/day
4–6 weeks
TCAs (desipramine, nortriptyline
25 mg at bedtime
↑ by 25 mg/day every 3–7 days
150 mg/day
6–8 weeks, with ≥2 weeks at max. tolerated dosage
Topical lidocaine
Max. 3 5% patches/day for 12 h max.
None needed
Max. 3 patches/day for 12–18 h max.
3 weeks
Speaker’s Notes
This slide provides guidance on initiating and titrating first-line medications for neuropathic pain based on the 2010 International Association for the Study of Pain (IASP) recommendations for the pharmacological management of neuropathic pain.
Local product information for each drug should be consulted for further details and specific indications, contraindications and warnings.
Reference
Dworkin RH et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010; 85(3 Suppl):S3-14.
SNRI = serotonin-norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant
Dworkin RH et al. Mayo Clin Proc 2010; 85(3 Suppl):S3-14.

52. But… Patients with Chronic Pain of Just One Type of Pain Pathophysiology May be Rare
Patients may have different pathophysiologic mechanisms contributing to their pain
e.g., complex regional pain syndrome has multiple potential mechanisms, including nerve injury and inflammation – “mixed pain state”
Therapies that will work better for a particular patient are likely to depend on the mechanisms contributing to the patient’s pain
Speaker’s Notes
Within any diagnostic category, individual patients may have different pathophysiologic mechanisms contributing to their pain.
Both the drug and non-drug therapies that will work better for a particular patient are likely to depend on the mechanisms contributing to the patient’s pain.
Thus, the assessment of pain has to include the determination of the type(s) of pain pathophysiology contributing to the patient’s pain.
References
Dowd GS et al. Complex regional pain syndrome with special emphasis on the knee. J Bone Joint Surg Br 2007; 89(3):
Vellucci R. Heterogeneity of chronic pain. Clin Drug Investig 2012; 32(Suppl 1):3-10.
Patients with mixed pain may benefit from combination therapy
Dowd GS et al. J Bone Joint Surg Br 2007; 89(3):285-90; Vellucci R. Clin Drug Investig 2012; 32(Suppl 1):3-10.

53. Discussion Question
what treatment approach would you take with a patient suffering from mixed pain due to complex regional pain syndrome?
Speaker’s Notes
Ask the question shown on the slide to participants to stimulate discussion.

54. Complex Regional Pain Syndrome
What is it?
Exaggerated response to trauma, characterized by intense prolonged pain, delayed recovery of function, vasomotor disturbances and trophic changes
Causes are unclear, but may include exaggerated local inflammatory response, nerve injury and involvement of the central and peripheral nervous systems
How common is it?
Thought to occur in 1 in 2000 cases of limb trauma
How should it be treated?
Physiotherapy is the mainstay of treatment
Combination of pharmacological agents may be necessary
Speaker’s Notes
As described on this slide, complex regional pain syndrome is one example of a possible mixed pain condition.
Management of this condition may be complex and referral to a specialist is recommended.
Reference
Dowd GS et al. Complex regional pain syndrome with special emphasis on the knee. J Bone Joint Surg Br 2007; 89(3):
Dowd GS et al. J Bone Joint Surg Br 2007; 89(3):

55. Key Messages
Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system
Up to 10% of the population may suffer from neuropathic pain, which is associated with significant patient-reported burden
Neuropathic pain can be distinguished from nociceptive pain through common verbal descriptors and simple bedside tests
Several easy screening tests are also available
Non-pharmacological therapies, including patient education, are important components of neuropathic pain management
When it comes to pharmacotherapy, most treatment guidelines consider antidepressants and α2δ ligands as first-line therapy for most types of neuropathic pain
Speaker’s Notes
This slide can be used to summarize the main points of this presentation.