Pain is always a personal experience that is influenced to varying degrees by biological, psychological, and social factors.

• Pain and nociception are different phenomena. Pain cannot be inferred solely from activity in sensory neurons.
• Through their life experiences, individuals learn the concept of pain.
• A person’s report of an experience as pain should be respected.
• Although pain usually serves an adaptive role, it may have adverse effects on function and social and psychological well-being.
• Verbal description is only one of several behaviours to express pain. Inability to communicate does not negate the possibility that a human or a non-human animal
• experiences pain.

The different pain types

There are six widely accepted pain types, of which neuropathic pain (NeP) is one of the most common types – especially among patients 50-years and older.^3,4,5

The IASP defines NeP as ‘pain caused by a lesion or disease of the somatosensory nervous system'. NeP affects between 7%-10% of the global population.^3,4

Other pain types include:⁴

• Nociceptive pain (due to actual tissue injuries such as burns, bruises, or sprains)
• Musculoskeletal (eg back or myofascial pain)
• Inflammatory (caused by autoimmune disorders eg rheumatoid arthritis or infections)
• Psychogenic (caused by psychologic factors such as headaches or abdominal pain caused by emotional, psychological, or behavioural factors)
• Mechanical (may be due to expanding malignancy).

Diagnostic criteria

According to the IASP, NeP is a clinical description and not a diagnosis, which requires a demonstrable lesion or a disease that satisfies established neurological diagnostic criteria.¹

It is common when investigating NeP 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.¹

The IASP differentiates between:

• Central NeP: caused by a lesion or disease of the central somatosensory nervous system (eg fibromyalgia, multiple sclerosis, stroke, or spinal cord injury). Lesions can occur anywhere along the path from the dorsal horn of the spinal cord to the cortex in the somatosensory system.^1,5,6
• Peripheral NeP: caused by a lesion or disease of the peripheral somatosensory nervous system (eg chemotherapy-induced neuropathy and diabetic neuropathy). Lesions range from the dorsal root ganglion and its spinal cord connections to the periphery. Generally, the smaller fibres such as the myelinated A beta and delta fibres and the unmyelinated C fibres are affected.^1,6

What are the symptoms of NeP?

Symptoms of NeP include sensations of burning, tingling, lightning bolts of pain, sharp sensations, unpleasant cold sensations, and electric-like sensations.⁶

Touching the skin can cause allodynia (experiencing pain from a stimulus that normally is not painful) or hyperalgesia (an exaggerated pain response to a painful stimulus).⁶

Secondary symptoms and problems can include anxiety, depression, sleep disturbances as well as impaired quality of life.⁶

Between 20%-30% of patients develop chronic NeP (pain lasting >3 months). Chronic NeP is slightly more frequent in women (8%) than men (5.7%) in those >50-years (8.9%) versus those <50-years (5.6%). A common cause of chronic NeP is diabetic neuropathy. One large study showed that the prevalence of chronic NeP in patients living with diabetes is around 47%.^6,7

How is NeP treated?

The management of NeP focuses on treating symptoms and in certain conditions treating aetiological causes. Pharmacological treatments recommended as the first-line treatment include anti-depressants (tricyclic agents [TCAs], serotonin-norepinephrine reuptake inhibitors [SNRIs]), and anticonvulsants (gabapentin and pregabalin).^6,7

Effective non-pharmacological treatment modalities for chronic pain include behavioural therapy for short-term pain relief, cognitive behavioural therapy for reducing long-term pain and disability, hypnosis as an adjunctive therapy, guided imagery, diaphragmatic breathing, and music therapy.⁷

The latest guidelines (2015) from the IASP’s Neuropathic Pain Special Interest Group recommend gabapentin or pregabalin, TCAs, and the SNRIs, venlafaxine or duloxetine, as first-line treatment for NeP.^6,8

Second-line treatments include tramadol, topical lidocaine, or high-concentration capsaicin. Finally, strong opioids (morphine and oxycodone) and botulinum toxin-A are included as third-line treatments for peripheral NeP.⁸

How effective is pregabalin in the management of NeP?

A 2019 Cochrane review, which included 45 studies lasting two to 16 weeks and 11 906 participants, compared the efficacy of oral pregabalin doses of 150mg, 300mg, and 600mg daily with placebo. More than 85% of the participants had a diagnosis of either postherpetic neuralgia, painful diabetic neuropathy, or mixed neuropathic pain.⁹

Postherpetic neuralgia: more participants had at least 30% pain intensity reduction with pregabalin 300mg than with placebo (50% vs 25%), and more had at least 50% pain intensity reduction (32% vs 13%). More participants had at least 30% pain intensity reduction with pregabalin 600mg than with placebo (62% vs 24%), and more had at least 50% pain intensity reduction (41% vs 15%).⁹

Painful diabetic neuropathy: more participants had at least 30% pain intensity reduction with pregabalin 300 mg than with placebo (47% vs 42%), more had at least 50% pain intensity reduction (31% vs 24%), and more had patient global impression of change much or very much improved (51% vs 30%). More participants had at least 30% pain intensity reduction with pregabalin 600mg than with placebo (63% vs 52%), and more had at least 50% pain intensity reduction (41% vs 28%).⁹

Mixed or unclassified post‐traumatic NeP: more participants had at least 30% pain intensity reduction with pregabalin 600mg than with placebo (48% vs 36%), and more had at least 50% pain intensity reduction (34% vs 20%).9

Central NeP: More participants had at least 30% pain intensity reduction with pregabalin 600mg than with placebo (44% vs 28%) and at least 50% pain intensity reduction (26% vs 15%).⁹

Recommendations when prescribing pregabalin in primary care

While many patients may benefit from treatment with pregabalin, they are often treated with suboptimal doses, write Freynhagen et al. According to the authors, this may be due to the fact that general practitioners or primary care physicians are uncertain about initiating and/or titrating therapeutics used for chronic NeP.¹⁰

In 2017, an international expert panel of chronic pain specialists convened to discuss dosing and adherence challenges with pregabalin in general practice. Table 1 summarises their key recommendations.¹⁰

Table 1: Summary of key recommendations for prescribing and titrating pregabalin for the ongoing management of patients with NeP in primary care¹⁰

REFERENCES

 International Association for the Study of Pain. Terminology. https://www.iasp-pain.org/resources/terminology/#Neuropathicpain

1. Szok D, Tajti J, Nyári A, Vécsei L. Therapeutic Approaches for Peripheral and Central Neuropathic Pain. Behav Neurol, 2019.
2. International Association for the Study of Pain. Revised definition of pain. https://www.iasp-pain.org/wp-content/uploads/2022/04/revised-definition-flysheet_R2.pdf
3. Dydyk AM, Conermann T. Chronic Pain. [Updated 2022 Nov 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK553030/
4. Dydyk AM, Givler A. Central Pain Syndrome. [Updated 2022 Nov 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK553027/#:~:text=Central%20pain%20syndrome%20is%20neuropathic,and%20musculoskeletal%20disorders%20as%20well
5. Murphy D, Lester D, Smither C, et al. Neurogenic Pain Disorders. Neurorehabilitation, 2020.
6. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol, 2015.
7. Hange N, Poudel S, Ozair S, et al. Managing Chronic Neuropathic Pain: Recent Advances and New Challenges. Neurology Research Internation, 2022.
8. Derry S, Bell RF, Straube S, et al. Pregabalin for neuropathic pain in adults. Cochrane Database Syst Rev, 2019.
9. Freynhagen R, Baron R, Kawaguchi Y, et al. Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration. Postgraduate Medicine, 2020.