1. Introduction: Neuropathic pain is a debilitating form of chronic pain. Learn more about it in this storyboard.
(navigate through the storyboard by clicking on the panels in this top row).
Imagine having a pain that has been described as being ‘Worse than death’. A pain that may feel like your ‘skin is on fire’, and at the same time the painful area may be ‘numb’. In some cases even the lightest of touches, such as your clothes on your skin, may be excruciatingly painful. This is what it can feel like to have neuropathic pain.
This storyboard will introduce you to this unusual type of chronic pain and its treatment.
Navigation: Every section of the storyboard consists of an interactive plot on the left (try it out by hovering your mouse arrow over the adjacent plot), and a text panel on the right. The text panel expands on the question stated in the numbered navigation panel above, and provides a legend for the figure. The figure provides illustrative data that complements the text.
Interactive plot: What does neuropathic pain feel like?.
The plot shows the relative frequency of terms used by 89 individuals with various causes of nervous system injury (e.g., traumatic nerve injury, post-herpetic neuralgia, polyneuropathies, stroke pain; block size is proportional to frequency). ‘Burning’ was the most commonly used term, but most patients use several terms to describe their pain1.
Created by: painblogR 
2. How common is neuropathic pain? Neuropathic pain is estimated to affect 7 to 10% of adults globally; that’s between 518 to 740 million people2.
Neuropathic pain is caused by damage to the sensory pathways and structures of the nervous system. This damage may occur as a result of physical trauma (e.g., motor vehicle accidents, war-related trauma to combatants and non-combatants, surgery), or as a secondary consequence of other medical conditions (e.g., diabetes mellitus, HIV, malnutrition, stroke, tumours) and their treatments (e.g., cancer chemotherapy).
Interactive plot: Prevalence of neuropathic pain in the general population
The centre horizontal lines show the reported prevalence of neuropathic pain. The boxes show the bootstrap 95% confidence interval of the prevalence (10,000 resamples), and the whiskers show the maximum and minimum values obtained from the resampling. The dashed line shows the bootstrap mean across all six studies (n = 38,422), and line & fill colour quantifies the sample size.
(Click the flag to access the related PubMed entry)
Created by: painblogR
3. Are we winning the war on neuropathic pain? No. The burden of neuropathic pain is likely to increase in the future, with developing countries being worst affected.
Two persistent global trends are an aging population3 and the rising prevalence of diabetes mellitus4. Both these factors are major risks for neuropathic pain, and mean that neuropathic pain is likely to increase in prevalence and importance in the future.
Developing countries have the highest rates of increase in population aging and cases of diabetes mellitus. Moreover, these countries face a greater burden of disease from other common causes of neuropathic pain such as trauma, HIV/AIDS, and leprosy than do developed countries5. Thus, more poorly resourced nations are likely to increasingly shoulder a disproportionate share of the global burden of neuropathic pain.
Interactive plot: Estimated and projected global burden of diabetes mellitus and painful diabetic polyneuropathy
Estimated number of cases of diabetes mellitus (blue) and painful diabetic polyneuropathy (DPN) (orange) between 1985 and 2013. Projected number of cases up to 2035 are highlighted in the grey block6. The number of DPN cases is based on estimates of between 10 and 20% of diabetics developing a painful neuropathy7.
Created by: painblogR
4. Why does neuropathic pain matter? Neuropathic pain has a significant adverse impact on life, health and function; even more so than other causes of chronic pain8.
Neuropathic pain has a significant adverse impact on all measured aspects of life, health and function. This impact is greater than the impact of chronic, non-neuropathic pain, even when adjusting for pain intensity8. In one study, 17% of people reporting neuropathic pain rated their quality of life as ‘worse than death’, according to the validated EQ5D health-related quality of life measure9. The average quality of life scores in the presence of neuropathic pain are comparable to those with severe depression, with poorly-controlled diabetes mellitus, and after recent myocardial infarction8.
Interactive plot: Health-related quality of life in people with and without chronic pain
Ratings of health-related quality of life from a population survey in Scotland8. Ratings are shown for people without chronic pain (green, n = 1,537), with chronic non-neuropathic pain (blue, n = 1,179), and chronic neuropathic pain (orange, n = 241). Across all eight domains, having neuropathic pain was associated with significantly poorer quality of life compared to having no chronic pain or having chronic non-neuropathic pain.
Created by: painblogR
5. Do we have effective medicines? Neuropathic pain can be difficult to treat, but there are specific classes of drugs with proven efficacy in managing the pain10.
A recent GRADE assessment of pharmacological treatments for neuropathic pain recommended10:
FIRST LINE: Tricyclic antidepressants (e.g., amitriptyline), serotonin and noradrenaline reuptake inhibitors (duloxetine, venlafaxine), and \(\alpha2\delta\)-calcium channel ligands (gabapentin, pregabalin).
SECOND LINE: Tramadol, 5% lidocaine patches \(^\dagger\), 8% capsaicin patches \(^\dagger\).
THIRD LINE: Strong opioids (e.g., morphine and oxycodone), and botulinium toxin A \(^\dagger\).
\(\dagger\): Recommended for neuropathic pain of peripheral origin only
Interactive plot: Recommended first-line treatments for neuropathic pain
Point estimates and 95% confidence intervals of the number needed to treat (NNT) for first-line therapies for neuropathic pain. The shading colour quantifies the total number of people included in randomized control trials involving each drug/drug class.†: NNT quantifies the effectiveness of an intervention in terms of the number of people that need to be treated with a drug before one person achieves significant benefit relative to the control (1 is the best NNT). Here, significant benefit was defined as at least 50% pain reduction compared to placebo, and NNT values > 11 were considered as no clinically significant benefit.
Created by: painblogR
6. Are these medicines widely available? No, national essential medicines lists of developing countries typically do not provide good coverage of the recommended medicines11.
The WHO has urged its members to ensure, "the availability of essential medicines for the management of symptoms, including pain". But, a recent audit of 112 national essential medicines lists (NEML) identified that ~66% of countries had only one class of first-line agent (typically tricyclic antidepressants), and ~50% had only one second-line agent (typically tramadol, a weak opioid), included on their NEMLs11.
This means that should a patient fail to respond to initial therapy, have significant side effects, or have contraindications to a drug’s use, there are no or limited alternative agents available to switch to, or add-on to the initial agent.
Interactive plot: NEML-listings of recommended drug classes.
For each level of recommendation, the colour intensity quantifies the number of drug classes listed on a countries NEML (click on a country to view detailed information). Only low- and middle-income countries with publically available data are highlighted, all other countries are shaded grey.
†: TCA = tricyclic antidepressants (typically amitriptyline); α2δ-ligand = α2δ-calcium channel ligands (gabapentin and pregabalin); SNRI = serotonin and noradrenaline reuptake inhibitors (duloxetine and venlafaxine). ‡: Weak opioid = tramadol; Topical agent = 5% lidocaine cream/patch, 8% capsaicin patch (not listed on any NEMLs). ⁕: Strong opioid = morphine or oxycodone; Other agent = Botulinium toxin A (not listed on any NEMLs)
Created by: painblogR
7. What can be done to increase treatment availability? One option is to increase access by getting more classes of effective medications included on the WHO Model List of Essential Medicines.
The WHO policies and publications on essential medicines inform developing countries national essential medicines lists12 and are associated with improved quality use of medicines13. Thus, getting first-line medicines for the treatment of neuropathic pain included on the WHO Model List of Essential Medicines provides an indirect method to increase global access to effective treatments, and to increase awareness of neuropathic pain as a public health issue.
The International Association for the Study of Pain (IASP), working together with its Special Interest Group on Neuropathic Pain (NeuPSIG) and the International Association for Hospice and Palliative Care (IAHPC), are therefore applying to have the first-line medication, gabapentin included on the WHO Model List of Essential Medicines.
Draft copy of the application
Click on the image on the left to download a draft copy of the application. You can also access all the files used to generate the application, including the figures, from this GitHub repository.
The source code for this storyboard can be accessed by clicking ‘source code’ on the right side of the navigation bar.
Created by: painblogR