Neuropathic Pain

Neuropathic pain is a multidimensional entity that continues to present a challenge to medical professionals with regards to its diagnosis and management. In recent years there has been an emphasis on the use of pain descriptors to aid diagnosis, but the lack of pathognomonic terms and overlap of descriptors between neuropathic and nociceptive pain conditions means that neuropathic pain continues to be poorly recognised and under-treated.

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Neuropathic Pain Summary

The reasons why only some patients with nerve lesions develop neuropathic pain are still unknown. Risk factors such as age, gender, pain intensity before and after the lesion, and emotional and cognitive features indicate that there are multiple factors other than the nerve lesion itself that contribute to manifestation of chronic pain. Differences in the extent of the lesion of certain subgroups of nociceptive afferent pathways might also be a predictor for development of neuropathic pain, as well as genetic determinants.

Classification Of Chronic Pain

The classification of chronic pain falls into three broad categories: pain owing to tissue disease or damage (nociceptive pain, such as osteoarthritis), pain caused by somatosensory system disease or damage (neuropathic pain) and coexistence of nociceptive and neuropathic pain (mixed pain). Various nerve damaging stimuli in the peripheral or central nervous system can lead to neuropathic pain, yet the clinical manifestation of the pain is similar across the different neuropathic syndromes and causes. Patients typically have paradoxical sensory perceptions with pain as a dominating positive symptom combined with lesion-induced reduced sensations.

The characteristic sensory abnormalities are crucial findings to correctly diagnose neuropathic pain and to distinguish this from other pain types. The key challenges in development of a targeted holistic approach to neuropathic pain management include appropriate diagnosis of the cause of pain, identification of the type of pain and assessment of the importance of its various components, and determination of appropriate treatment.


Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, either at the peripheral or central level. This new definition proposed by The Special Interest Group on Neuropathic Pain (NeuPSIG), of the International Association for the Study of Pain (IASP), replaces ‘dysfunction’ in the IASP definition with ‘disease’, to distinguish neuropathic pain from pain caused by neuroplastic changes in response to strong nociceptive stimulation.


Accurate data are unavailable due to the lack of agreed definitions and diagnostic criteria for neuropathic pain. A UK study published in 2006 estimated the prevalence of chronic pain that was of predominantly neuropathic origin to be 2% in adults. This represented 17% of those with chronic pain, and was more common among women, older adults and those with a poor socioeconomic status.


Research indicates that lesion of afferent pathways is necessary for development of neuropathic pain. Furthermore, data clearly indicate that several mechanisms can lead to neuropathic pain. Importantly, many of these mechanisms do not depend on the cause of the disease: the same mechanism can be found in different diseases (eg, in postherpetic neuralgia and in painful polyneuropathy). In one individual patient, different mechanisms might be involved and different mechanisms could lead to the same symptom. Because different treatment regimens are needed for different pain mechanisms, a mechanism-based treatment approach can lead to efficient analgesia.

Ectopic Nerve Activity

Sensing ongoing spontaneous pain and paroxysmal shooting pain in the absence of any external stimulus is caused by ectopic impulse generation within the nociceptive pathways. Increasing levels of mRNA for voltage-gated sodium channels seem to correlate with ectopic activity, and increased expression of sodium channels in lesioned and intact fibres might lower action potential threshold until ectopic activity takes place. Similar changes within second-order nociceptive neurons are thought to occur after central lesions, leading to central neuropathic pain.

Nerve injury also induces upregulation of various receptor proteins such as the transient receptor potential V1 (TRPV1). TRPV1 is located on subtypes of peripheral nocicepive endings and is physiologically activated by noxious heat at about 41°C.31 After a nerve lesion, TRPV1 is downregulated on injured nerve fibres but upregulated on uninjured C-fibres. This novel expression of TRPV1 and additional sensitisation to heat by intracellular signal transduction might lead to spontaneous nerve activity induced by normal body temperature, if the threshold of TRPV1 is reduced to below 38°C.

Central Sensitisation

Secondary allodynia and hyperalgesia (ie, evoked pain, in particular dynamic mechanical allodynia) in the area adjacent to the innervation territory of the lesioned nerves requires involvement of the CNS. Central sensitisation might develop as a consequence of ectopic activity in primary nociceptive afferent fibres and structural damage within the CNS itself might not be necessarily involved.

Assessment And Diagnosis Of Neuropathic Pain

Several screening tools based on verbal pain description, with or without clinical examination, have been developed and validated in neuropathic pain. Their attraction lies in ease of use for patients and professionals alike, and their ability to help non-specialists in the diagnosis of neuropathic pain. However, screening tools fail to identify up to one in five patients with clinician-diagnosed neuropathic pain, indicating that they cannot replace clinical judgment.

Clinical examination is aimed at providing supporting evidence for altered functioning of the nervous system. Sensory testing is the most important part of examination and should include testing of touch, vibration, pinprick and cold and warmth. Comparing findings from the painful area with the contralateral side may aid in diagnosis. It is important to note that positive (allodynia, hyperalgesia) and negative (hypoesthesia, hypoalgesia) sensory phenomena may also be reported in non-neuropathic pains.

Clinical examination alone is less sensitive than several complementary tests to document the presence of a somatosensory lesion. For example, electroneuromyography has been shown to be superior to clinical examination alone for the diagnosis of peripheral neuropathy.

Management Of Neuropathic Pain

Treatment of neuropathic pain is still a challenge because many patients do not experience suffcient pain relief, as determined from clinical experience and from clinical trial outcomes. This difficulty in treatment might be a result of the heterogeneity of neuropathic pain mechanisms and the frequently coexisting psychological and emotional aspects of chronic pain.

When starting symptomatic treatment, education of patients, including information on neuropathic pain, the treatment plan, and possible side-effects of drugs, is important to increase patient compliance. To avoid unrealistic expectations from patients on efficacy and tolerability, realistic treatment goals should be determined. Pain reduction of at least 30% is generally accepted to be a clinically meaningful result. In addition to pain, both sleep disturbance and health-related quality of life, including social and emotional functioning, should be assessed when analysing analgesic efficacy. Additionally, coexisting depression and anxiety might hinder pain treatment and should be identified and targeted for specific treatment. In clinical practice, this complexity is taken into account by an interdisciplinary therapeutic approach, including pharmacological and non-pharmacological treatment regimens, such as cognitive behavioural, physical, and occupational therapy.

Pharmacological Management

Pharmacological management remains the most important therapeutic option for chronic neuropathic pain, but results continue to remain unsatisfactory despite the significant increase in the number of published trials. Neuropathic pain drugs generally have poor efficacy: one reason is that efficacy is measured using number needed to treat (NNT) and number needed to harm (NNH), and this approach has a number of limitations.

  • Multidimensional nature of neuropathic pain
  • Lack of disease-modifying drugs
  • Relatively few head-to-head drug comparisons

A number of guidelines have been published regarding pharmacological management of neuropathic pain. Various types of drugs, including antidepressants with norepinephrine and serotonin reuptake inhibition, calcium channel alpha2-delta ligands and opioid analgesics have been shown to have consistent efficacy in randomised controlled clinical trials and meta analyses. Topical treatments like lidocaine patches and Qutenza (Capsaicin 8%) have a role in selective cases.

Combination Therapy

In clinical practice, a combination of two or more drugs is often needed to achieve satisfactory pain relief, although there have been few trials done to support this clinical observation.

Tens Therapy

Transcutaneous electrical stimulation is commonly used for non-invasive therapy and, although the evidence level is low, the benefit to risk ratio is favourable and, therefore, this stimulation is a therapeutic option in patients with neuropathic pain.

Interventional Treatments

Various interventional treatments can aid the management of neuropathic pain:

  • Epidural injections
  • Caudal injections
  • Peripheral nerve blocks
  • Botox injections
  • Spinal cord stimulators
  • Peripheral nerve stimulators
  • Local infiltration
  • Pulsed radiofrequency treatments

Percutaneous Electric Nerve Stimulation (pens Therapy)

Percutaneous Electrical Nerve Stimulation (PENS) is a relatively new electro analgesic therapy. It differs from TENS in needle-like probes is inserted percutaneously into an area of tissue, and then electrical current is passed through the probe to stimulate the nerves. AS it bypasses the resistance of the cutaneous barrier and delivers the electrical stimulus in closer proximity to the nerve endings, it may be more effective. Compared with implantable peripheral nerve stimulation, the PENS technique is less invasive, less costly, and less risky. PENS can be a useful non-pharmacological alternative to medications.

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Dr Murli Krishna

Consultant Pain Medicine