Neuropathic Pain – Symptoms, Treatment & Clinical Trials

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Chronic pain falls into a number of categories. Two major categories are Nociceptive and Neuropathic pain. Further classification depends on where the pain is located and what is causing it (i.e. cancer-related, musculoskeletal, somatic or visceral, etc). Many chronic painful conditions will involve mixed nociceptive/neuropathic/other pain types. In this article, we briefly explain the differences between the two major categories of pain and expand on neuropathic pain.

Nociceptive vs Neuropathic Pain

Nociceptive Pain

Nociceptive pain is pain due to tissue damage. Nociceptors are sensory nerve cells residing in tissues, particularly the skin. They detect and respond to tissue damage and dangerous signals that may lead to tissue damage, such as extreme temperature, pressure, chemicals and toxins. They transmit signals to the central nervous system to evoke the sensation of pain.

Nociceptive pain typically results from an injury, such as a wound, burn, bruise, sprain, fracture, and so forth. The clinical characteristics of nociceptive pain depend on the source of the pain and may be described as:

  • Skin / subcutaneous tissues (somatic pain): stinging or burning;
  • Bones, joints, ligaments, muscles etc (also somatic pain): aching;
  • Internal organs (visceral pain): dull and deep, often referred (felt at a location away from the actual source of pain).

Most cases of nociceptive pain are acute, usually resolving over time as the body heals the damaged tissue; however, nociceptive pain may also be chronic. Chronic nociceptive pain may be due to arthritis, osteoporosis or cancer, for example.

Neuropathic Pain

Neuropathic pain is pain due to damage to or dysfunction of the somatosensory nervous system (which is part of the nervous system that responds to sensory information on the outside and inside of the body, such as touch, temperature, pressure and pain). A simplified, older definition, is pain due to nerve trauma or dysfunction (i.e. “nerve pain”).

Neuropathic pain can be due to direct injury to or irritation of a nerve, spinal cord injury, spinal disease or degeneration, chronic inflammation, cancer, chemotherapy, virus activity, dietary factors, just to name a few. In some cases, neuropathic pain may develop without any obvious cause.

Neuropathic pain is associated with “new and strange sensations”. Clinical characteristics of neuropathic pain include:

  • Burning (or freezing);
  • Electric shock-like pain;
  • Prickling or tingling (i.e. pins-and-needles);
  • Numbness.

Neuropathic Pain Conditions

There are numerous conditions that have a major or significant neuropathic pain component. Below are some examples.

Peripheral Neuropathy

Peripheral neuropathy is a term used to describe a range of conditions in which peripheral nerves (outside of the central nervous system) behave abnormally due to some form of nerve damage/trauma/irritation. This may be caused by some underlying condition or disease (e.g. diabetes, cancer, virus infection), or it could be a side effect of prolonged exposure to some drug/treatment (e.g. chemotherapy), or even dietary factors (e.g. alcoholism, vitamin deficiency). Peripheral neuropathy is often associated with pain. Specific examples of peripheral neuropathies are:

  • Peripheral Diabetic Neuropathy (PDN) – this affects approximately 26% of people with diabetes type 2. It most commonly affects the feet and hands. Read more here.
  • Postherpetic Neuralgia (PHN) – this affects approximately 8% of people who have had shingles (a herpes zoster episode). Read more here.
  • Trigeminal Neuralgia – a condition that affects the trigeminal nerve (aka the fifth cranial nerve, which is the largest nerve in the head) and that causes facial pain. The pain may be severe and episodic, or constant and aching.

Chronic Low Back and/or Leg Pain

Chronic low back / leg pain typically involves a mixture of pain types. The nociceptive pain component may be the result of injury, stress and/or inflammation to the muscles, joints, ligaments, tendons or fascia within and around the spine. There may not be a neuropathic pain component, but if there is, it could be the result of injury, irritation and/or inflammation to the spinal nerve roots or the discs, which may be due to or complicated by an underlying disease.

Central Pain

Neuropathic pain conditions involving the somatosensory system of the central nervous system include post-stroke pain and spinal cord injury-related neuropathic pain.

Diagnosing & Assessing Neuropathic Pain


The most common symptoms of neuropathic pain, as listed above, are: burning pain, electric shock-like pain, prickling or tingling pain (i.e. pins and needles – aka paraesthesia) and numbness.

Clinical Indicators

Signs of neuropathic pain that can be assessed by a physician during a physical examination include the following:

  • Allodynia – pain from a normally non-painful sensation (i.e. soft touch).
  • Hyperalgesia – unusually high pain response to a painful stimulus (i.e. a pinprick).
  • Hypoalgesia – low pain response to a painful stimulus.
  • Vasomotor/vascular dysfunction – i.e. changes in blood flow.
  • Sudomotor dysfunction (i.e. excessive sweating).
  • Sensory dysfunction (i.e. loss of sensation to temperature / vibration / soft touch).
  • Muscle atrophy / weakness.
  • Oedema / swelling.
  • Trophic changes (i.e. abnormal hair / nail growth).


Several questionnaires have been developed for the purpose of specifically identifying neuropathic pain, such as the following:

  • Douleur Neuropathique en 4 (DN4) – French, 4 questions with a total of 10 items.
  • Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) – the first neuropathic pain tool developed, 5 questions on symptoms and 2 questions on sensory testing.
  • Neuropathic Pain Questionnaire (NPQ) – 10 questions on sensations and 2 questions on affect.
  • PainDETECT – self-reported, developed for patients with back pain, 7 questions, includes a diagram.

Diagnostic Tests

Whilst not specific for neuropathic pain, several clinical or laboratory diagnostic tools have been developed as methods of assessing nervous system dysfunction, such as:

  • Nerve Conduction Studies (NCS) – involves electrical activation of peripheral nerves and measurement of their response to assess motor and sensory nerve function.
  • Quantitative Sensory Testing (QST) – thermal skin tests accompanied by vibration to diagnose peripheral sensory disorders.

Treatments for Neuropathic Pain

Ultimately, treatment of neuropathic pain depends on the cause / specific condition and whether the condition involves mixed pain types and multiple/complex disease mechanisms. Chronic pain management generally requires a multi-treatment, multi-disciplinary approach. The following treatment options are designed to treat neuropathic pain specifically.


The following drugs are recommended for treatment of neuropathic pain:

  • Tricyclic antidepressants (TCAs) – amitriptyline;
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) – duloxetine, venlafaxine;
  • Anticonvulsants – gabapentin, pregabalin;
  • Topical treatments – capsaicin cream, lidocaine patch.

The use of opioids is controversial, namely due to their side effects and the lack of evidence to support their long-term effectiveness. Tramadol is an atypical opioid that may be useful.

Physical Therapy & Rehabilitation

Physical therapy and rehabilitation techniques, along with psychological support, if necessary, are important in the multimodal management of neuropathic pain, especially when medications are inadequate. Therapies that may be useful for neuropathic pain, depending on the specific condition, include:

  • Therapeutic exercise programs;
  • Cognitive behavioural therapy (CBT);
  • Mirror box therapy;
  • Graded motor imagery (GMI);
  • Transcutaneous electrical nerve stimulation (TENS).


Where medications and conservative therapies fail to help with neuropathic pain, certain interventional procedures may be considered, depending on the specific condition.

  • Nerve Blocks – An injection of local anaesthetic and corticosteroid into the site of the pain generating nerve.
  • Spinal Cord Stimulation (SCS) – An implantable electrical stimulation device with stimulating leads inserted into the epidural space of the spinal cord – Read more here.
  • Intrathecal Drug Therapy – An implanted drug delivery system that releases strong opioids and/or local anesthetic, directly to the intrathecal space (spinal fluid around the spinal cord).

Clinical Trials

Genesis Research Services conducts clinical trials for patients with neuropathic pain. If you live with neuropathic pain and are interested in participating in a clinical trial, click here to view our current studies or call us on (02) 4985 1860. If the current studies aren’t suitable for you, you may register your interest for future studies.

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14.  May S & Serpell M. “Diagnosis and assessment of neuropathic pain”. F1000 Medicine Reports 2009; 1:76.

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18.  Task Force on Professional Education. “Chapter 39 – Neuropathic Pain”. In: Core Curriculum for Professional Education in Pain. Ed. JE Charlton. Seattle: IASP Press, 2005. Accessed online (2018-09-20):   

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