What Is Neuropathic Pain

Neuropathic pain is an implication of many pathologies; it is chronic and affects the quality of life. So, it is of great importance to understand what it is, where it originates from and how it can be treated.

Introduction

Neuropathic pain is a term that refers to pain due to deficits of the somatosensory system, and its prevalence in humans is estimated to be around 7 to 10%.  The somatosensory system is responsible for the perception of stimuli that are generally associated with touch. It is the mechanism through which humans can perceive tactile stimuli, be it a caress or a painful stimulus. Moreover, it is implicated in the perception of temperature, and it is also part of the locomotor system in humans.¹ As a result, pathological conditions of the somatosensory system may lead to an altered or false perception of surrounding stimuli. Since neuropathic pain is usually a chronic condition, it can greatly affect everyday life, and so there is an evident need to understand the mechanism that governs its pathology to develop appropriate treatment methods.

The somatosensory system

The somatosensory system involves the regulation of three main activities: recognition of and response to environmental stimuli, recognition of and response to stimuli inside the body and orientation (meaning awareness of body position and balance maintenance). When a stimulus comes in contact with human skin, the first line of action is the responsibility of sensory nerve cells that carry mechanoreceptors that can recognise a variety of stimuli intensities.2 The input received by mechanoreceptors generates a ‘message’ that travels through the nerve cell across the length of the spinal cord and is then transferred into the brain neurons that are capable of ‘decoding’ that message and generating an appropriate response.3 For example, when we step on something sharp by accident, the pain is immediately perceived from the sensory neurons and carried to the brain, eliciting an instant response to retract our foot, as well as a relatively later response to be more mindful of our surroundings. As such, the somatosensory system serves as a protective mechanism that drives avoidance of harmful stimuli, and any damage to it may prove dangerous for the organism.

Understanding neuropathic pain

Types of neuropathic pain

The sensory nerve cells that initially receive mechanosensory input are branched in the body and constitute part of the peripheral nervous system (PNS). As previously mentioned, these cells drive sensory information to the brain, where other nerve cell populations carry out the task of transcribing the information received and driving a response to it. These brain nerve cells are localised in the central nervous system (CNS).³ Damage in either the PNS or the CNS may lead to neuropathic pain, which is referred to as peripheral or central neuropathic pain, respectively.⁴ Certain diseases have been associated with one type of neuropathic pain or the other. For instance, peripheral neuropathic pain has been observed in cases of patients with cancer who undergo chemotherapy and patients with diabetes, while central neuropathic pain has been linked with Parkinson's disease, multiple sclerosis, and cases of stroke. In addition, both neuropathic pain types can be a result of injury. Central neuropathic pain may be a result of spinal cord injury, but other injuries in peripheral nerve cells may lead to peripheral neuropathic pain. It should be noted that in many cases, the diagnosis of a certain disorder associated with neuropathic pain precedes the manifestation of pain. For such cases, some methods may help prevent neuropathic pain.¹

An interesting condition in which neuropathic pain is the main symptom is called phantom limb pain (PLP). Almost 80% of patients who have undergone limb amputation experience phantom pain, and in many cases, this occurs within the first month after amputation. Patients diagnosed with PLP usually describe pain as stinging or burning. Unfortunately, PLP is a chronic condition that affects the patients’ daily life. It should be noted that PLP is different from residual limb pain (RLP), which is localised at the remaining part of the amputated limb. On the contrary, in PLP, pain comes from the missing part of the limb, hence the term “phantom”.⁵

Differentiating neuropathic pain from nociceptive pain

Residual Limb Pain (RPL), which was described above, belongs to the more general term ‘nociceptive pain’. Nociceptive pain is distinguished from neuropathic pain, as it is solely associated with injury and tissue damage and might be treated with anti-inflammatory drugs. Nociceptive is also different to neuropathic pain in the affected patients’ description of the sensation, which is painful, albeit familiar.⁶

Symptoms and diagnosis

Symptoms linked with neuropathic pain

Neuropathic pain may be associated with any of three symptoms: allodynia, hyperalgesia and paresthesia.

• Allodynia is the condition in which pain is evoked by a normally non-painful stimulus. For example, being touched by a feather is normally painless, sometimes even barely noticeable. However, in cases of neuropathic pain, such a light touch can be painful.⁷
• Hyperalgesia is a term referring to enhanced pain provoked by a normally painful stimulus. The term is usually associated with pain sensitivity in a previously injured area. This applies to situations when, even after a mild injury, touching the area surrounding the injured tissue causes more pain than it normally would. Pain to bruised body parts also falls under the category of hyperalgesia.^{7, 8}
• Paresthesia is a term used to describe a burning or prickling sensation which is usually felt on limbs, though it can manifest in any body part.⁷ Paresthesia also includes the normal condition of the feeling of “pins and needles” that people may experience when they hold their limbs in one position for too long.

Quality of life

Unfortunately, the aforementioned symptoms of neuropathic pain have a negative effect on the patient’s everyday life as they affect physical abilities, emotions and cognition.¹ Functional limitations may lead to anxiety and depression, which in turn affect cognitive tasks. As a result, therapeutic methods must be developed to treat patients with neuropathic pain.

Diagnosis of neuropathic pain

There are three stages in the diagnosis process of neuropathic pain. Categorisation of cases into one of the stages depends on the certainty that a case suffers from neuropathic pain. More specifically, neuropathic pain is considered a “possible” cause of symptoms if the patient already suffers from a known pathological condition, disorder or disease that is known to be associated with neuropathic pain. In cases that show clinical symptoms to be examined, if the results of the examination indicate neuropathy as the cause, then neuropathic pain is considered “probable”, and treatment for neuropathy may be administered to patients. In order to get a “definite” diagnosis of neuropathic pain, laboratory, neuroimaging or neurophysiological tests must be carried out.

Several methods have been developed to aid diagnosis of neuropathic pain. Questionnaires are among these methods, and they usually include questions about the sensation of the pain, the stimulus that triggers pain, and the general feeling provoked. Skin biopsies are also a method of neuropathy testing, as they allow for the detection of damage in the nerve cells of the peripheral nervous system. However, skin biopsies and neuroimaging tests are performed at the later stages of diagnosis after other examinations and tests that assess sensory performance have already been carried out.¹

Management and treatment

Treatment of neuropathic pain remains a challenge mainly because of three reasons: first of all, the maybe obvious choice of widely-used analgesic drug administration to treat pain does not apply to neuropathic patients unless there is inflammation; second, the cause of neuropathic pain may vary, and even if the cause is known and can be treated, said treatment may not affect neuropathic pain; and third, clinical studies on neuropathic pain treatment are limited.

Even though analgesic drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) are not effective, compounds that target neurotransmitters (gamma-aminobutyric acid (GABA) and serotonin) are so far among the best candidates for neuropathy treatment. For instance, a couple of antiepileptic drugs that target GABA are regarded as the best option to treat peripheral neuropathic pain so far. In addition, a few studies support the notion that treating neuropathy with a combination of drugs instead of just one may be preferable. However, the efficacy of existing pharmacological treatments for neuropathic pain is low. Less than half of the patients with neuropathic pain are positively affected by such treatments.¹

Current pharmacological treatments for most cases include:

• Anticonvulsants
• Tricyclic Antidepressants (TCAs)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Topical agents (e.g. lidocaine)

In addition to, or instead of pharmacological treatments, other methods might be used, such as electrical stimulation of neuronal regions.⁹ Contrary to brain stimulation, spinal cord stimulation is more commonly used for pain relief and, combined with pharmacological treatment, yields long-term results in the alleviation of pain. Moreover, physical exercise with certain techniques is also considered to aid in the management of neuropathic pain.1 The mirror technique is effective in pain relief of patients with amputated arms. This technique simply requires the patient to look into a mirror so that their reverse image will excite the false perception that the amputated arm moves when the patient moves their other arm.¹⁰ Last but not least, psychological techniques are also facilitated in the effort to manage neuropathic pain and alleviate symptoms, mainly emotional and cognitive symptoms.¹

Summary

Neuropathic pain is a chronic condition that may be caused by a variety of pathologies and many disorders. Although various causes lead to neuropathy, any damage directly associated with it is localised in the nervous system, either the peripheral or the central nervous system. No matter the specific area affected, the symptoms associated with neuropathic pain generally manifest as altered perception of sensations, such as touch, in a way that interferes with everyday life. Despite the development of diagnosis tools, treatment of neuropathic pain is still an ongoing study. While numerous medications and non-pharmacological treatments are already being used, there is room for efficacy improvement.