Generality
Neuropathic pain, or neuralgia, is a chronic painful sensation that occurs as a result of a deterioration or malfunction of the nerves of the peripheral nervous system (peripheral neuropathy) or structures of the central nervous system.
The causes of this condition are numerous. These include nerve compression, some infectious diseases, diabetes and multiple sclerosis.
Therapy is based on treating the triggers and treating the symptoms.
Brief reminder of the nervous system
The nervous system is a set of organs, tissues and nerve cells (neurons), capable of receiving, analyzing and processing stimuli coming from inside and outside the body.
At the end of the processing, the nervous system generates responses suited to the situation, which favor the survival of the organism to which it belongs.
The vertebrate nervous system consists of two components:
- The central nervous system (CNS): it is the most important part of the nervous system, a real data processing and control center. In fact, it analyzes the information arriving from the external and internal environment of the organism, then formulates the answers most appropriate to the above information.
It is made up of the brain and spinal cord. - The peripheral nervous system (PNS): is the "arm" of the central nervous system. In fact, his job consists in transmitting to the CNS all the information collected inside and outside the organism and in spreading all the elaborations originating in the CNS to the periphery.
Without the PNS, the central nervous system could not function properly.
What is neuropathic pain?
Neuropathic pain, or neuralgia, is a particular painful sensation, of a chronic nature, which arises as a result of damage or malfunction of the nerves of the peripheral nervous system or of the structures making up the central nervous system.
The adjective neuropathic and related terms (for example neuropathy) derive from the union of two words: "neuro", which refers to the nerves, and "pathic" (or "pathia"), which means affection or suffering.
To better understand: neurons, nerve fibers and nerves
Neurons represent the functional units of the nervous system. Their task is to generate, exchange and transmit all those (nerve) signals, which allow muscle movement, sensory perceptions, reflex responses, etc.
Typically, a neuron consists of three parts:
- A body or soma, where the cell nucleus resides;
- The dendrites, which are equivalent to antennae for receiving nerve signals generally coming from other neurons;
- The axons, which are extensions that act as diffusers of the nerve signal. They may or may not be enveloped in a whitish substance called myelin (myelin sheath).
An axon covered by its myelin sheath is also called a nerve fiber.
A nerve fiber is not a nerve: a nerve is a bundle of axons.
So, in light of this, a set of nerve fibers can make up a nerve.
According to the characteristics of the neurons that form them, the nerves can carry signals from the periphery to the central nervous system and / or vice versa, that is, from the central nervous system to the periphery.
CENTRAL AND PERIPHERAL NEUROPATHIC PAIN
If the damage or malfunction affects the brain and / or spinal cord (therefore the main structures of the central nervous system), it is referred to as central neuropathic pain.
Conversely, if the lesion or dysfunction affects one or more nerves of the peripheral nervous system, it is referred to as peripheral neuropathic pain. In such situations, the condition that induces peripheral neuropathic pain is termed peripheral neuropathy.
DIFFERENCES FROM HARMFUL PAIN
Neuropathic pain is different from the painful sensation experienced following a wound, burn, trauma, or strong pressure (such as that exerted by a tumor pushing on surrounding tissues).
In fact, in the second case, the painful signaling starts from cutaneous receptors - called nociceptive receptors - which send messages from the periphery to the central nervous system, informing the latter ", through a painful sensation, of something abnormal and dangerous for the" body.
The painful stimulus produced by nociceptive receptors is called nociceptive pain and, unlike neuropathic pain, it is an easier disorder to interpret, in terms of causes, and above all to cure.
Causes
Neuropathic pain is usually the result of an "alteration of the myelin sheath that lines the axons of a nerve. This process can occur for no identifiable reason - in this case it is also referred to as idiopathic neuropathic pain - or as a result of very specific conditions," morbid and non-morbid, such as:
- Compression of a nerve (or nerve compression). Abnormalities of blood vessels (for example, microaneurysms), ligaments, expanding tumors, or bones can compress (or pinch) a nearby nerve. Its squeezing can cause erosion of the myelin sheath of its axons, resulting in a loss of function by the nerve itself and a sensation of neuropathic pain.
They are the result of nerve compression - which then translates into neuropathic pain - situations such as: trigeminal neuralgia (characterized by compression of the trigeminal nerve), glossopharyngeal neuralgia (characterized by compression of the glossopharyngeal nerve) or carpal tunnel syndrome ( due to compression of the median nerve). - Certain infectious diseases involving the nervous system. Some viruses and bacteria are capable of invading and damaging nerve cells, including those making up the nerves.
Among the most well-known infections that can cause neuropathic pain, we remember herpes zoster (N.B: in these cases we also speak of post-herpetic neuralgia), AIDS, Lyme disease and syphilis. - Diabetic neuropathy. The high levels of glucose in the blood (hyperglycemia), typical of people with diabetes, damage the blood vessels that supply the nerves of the PNS with oxygen and nutrients. In the absence of oxygen and nutrients, any nerve, tissue or organ in the body suffers necrosis, or death.
Diabetes represents one of the main causes of peripheral neuropathy in countries of the Western World, such as Italy or the United Kingdom. - Multiple sclerosis. It is a chronic and disabling disease, which arises as a result of a progressive degradation of myelin belonging to the neurons of the central nervous system. Therefore, the resulting neuropathic pain is the result of a central neuropathy.
- The phantom limb syndrome. It is a particular morbid condition, characterized by the "abnormal sensation of persistence of a limb, despite the" amputation of the latter ".
To suffer, therefore, are people who, for some reason, have been amputated a part of the body (a foot, a hand, etc.).
Patients with this problem claim to still feel the missing limb and to perceive continuous pain against it. - Vitamin deficiencies induced by alcoholism or other situations of malnutrition. Vitamins (in particular B12, B1, B6, niacin and E) are essential for the good health of the nervous system, therefore their deficiency involves, among the various consequences, also the deterioration of the nerves of the peripheral nervous system and of the neurons of the central nervous system.
- Trauma to the spine or peripheral nerves. A major trauma can irreparably damage an important nervous organ such as the spinal cord or the nerves of the peripheral nervous system. Thus, trauma neuropathic pain can be both central and peripheral.
Very serious traumatic events are those that can occur during a spinal surgery, a fall, a car accident or a bone fracture. - A chemotherapy treatment to cure a tumor. Some widely used chemotherapy drugs, including cisplatin, vincristine, and paclitaxel, can cause a form of peripheral neuropathy, hence neuropathic pain.
- Prolonged exposure to toxic substances. Substances such as arsenic, insecticides, lead or mercury can cause neuropathic pain, due to a situation of peripheral neuropathy.
- The porphyrias. They are a group of diseases, almost always of a hereditary type, due to a "functional alteration of one of the enzymes that synthesize the so-called heme group. The heme group is a non-protein molecule, which forms a fundamental part of some proteins, including "blood hemoglobin, myoglobin and cytochromes.
- Chronic kidney disease. If the kidneys work poorly, there is a buildup of toxic substances in the body; these toxic substances are harmful to the nerves of the peripheral nervous system.
EPIDEMILOGY
Figure: Alcoholism is a possible cause of peripheral neuropathy, which, in turn, is a cause of neuropathic pain.
According to some statistical research, in the United States neuropathic pain affects between 3 and 8% of the population, while in the United Kingdom it affects about 7% of the inhabitants.
Elderly people suffer most from it (N.B: this applies to most of the countries of the world) who suffer from the aforementioned morbid conditions, responsible for neuropathies.
Symptoms and Complications
Usually, patients with neuropathic pain experience stabbing and / or burning painful sensations.
Furthermore, in association, they develop a particular sensitivity to painful stimuli and complain of tingling and numbness in the painful area (generally the extremities of the upper and lower limbs).
PARTICULAR SENSITIVITY TO PAIN: ALLODINIA AND HYPERALGESIA
People with neuropathic pain often experience allodynia and / or hyperalgesia.
In medicine, with these two terms s "identify exaggerated responses to painful stimuli.
To be precise, we speak of allodynia when pain is felt even as a result of stimuli that, under normal conditions, would be harmless and without consequences.
Instead, the word hyperalgesia is used to indicate all those situations in which there is a hypersensitivity to painful stimuli. In other words, even the slightest insults result in marked suffering.
COMPLICATIONS
If you do not intervene with adequate therapy, the symptoms of neuropathic pain can become increasingly intense and increasingly difficult to treat.
Diagnosis
Diagnosis of neuropathic pain is generally based on a careful physical examination (during which the doctor evaluates the patient's symptoms and medical history), a neurological evaluation, blood tests, and an "electromyography".
The use of further tests - such as CT, magnetic resonance imaging and nerve biopsy - occurs in special cases (for example if there is a suspicion of a tumor) and to collect further information.
The final purpose of such a long diagnostic process is to trace the causes of neuropathic pain or, better, the causes of peripheral neuropathy or CNS damage.
Only thanks to the knowledge of the reasons that produce the painful sensation of the nerves, it is possible to plan the most appropriate therapy.
Important note: the earlier the diagnosis (early diagnosis) is made, the lower the extent of the neuropathic pain and the consequences of nerve damage.
OBJECTIVE EXAMINATION
During the physical examination, the doctor asks the patient to describe in detail the type of pain felt. In addition, he asks him about the pathologies suffered in the past, the current illnesses, the working activity practiced and the drugs in use.
Treatment
Neuropathic pain therapy includes:
- The specific treatment of the factor triggering the damage to the nervous system (central or peripheral).
- The drug treatment of neuropathic pain itself.
- Various physical (or at least non-pharmacological) treatments of symptoms.
- A psychological treatment
TREATMENT OF TRIGGERING CAUSES
Although it is only in some cases resolutive of the problem, treating the cause of the onset of neuropathic pain is very important, because it can strongly slow down (if not stop) the progression of the underlying neuropathy.
For example, in the case of diabetes, it is essential to plan the right drug therapy (insulin or hypoglycemic drugs), to keep blood pressure controlled and to regulate body weight.
Treating the triggering causes does not mean re-establishing the conditions prior to their onset. This, in fact, is impossible, as the damage to the nervous structures is permanent.
This is one of the reasons that explains the need for early diagnosis.
PHARMACOLOGICAL TREATMENT
The best known and used pain relievers and anti-inflammatory drugs, such as paracetamol or ibuprofen, are not very effective against neuropathic pain.
We need more powerful medicines of a different nature.
In particular, doctors resort to:
- Antidepressants of the tricyclic group and of the serotonin and norepinephrine reuptake inhibitor group.
Strange as it may seem, these depression medications also relieve symptoms associated with neuropathic pain with some success.
Of the group of tricyclics, we remember amitriptyline, doxepin and nortriptyline. The effects of these drugs are never immediate; for example, amitriptyline shows the first results only at the 2nd-3rd week of administration and the maximum therapeutic power at the 4th-6th.
From the group of serotonin and norepinephrine reuptake inhibitors, duloxetine and venlafaxine relieve neuropathic pain (although less effectively than tricyclics). They are particularly suitable for diabetic neuropathy.
Main side effects of tricyclics: sleepiness, dry mouth (or dry mouth), decreased appetite, nausea and constipation.
Main side effects of serotonin and norepinephrine reuptake inhibitors: drowsiness, nausea, headache and abdominal pain.
- Antiepileptics (or anticonvulsants).
Antiepileptics are drugs generally administered in case of epilepsy.
Among these pharmacological preparations, those effective against neuropathic pain are gabapentin and pregabalin.
Usually prescribed as an alternative to antidepressants (N.B: they are associated only when both do not give the desired results), they show the first effects after several weeks of use.
Main side effects: drowsiness and dizziness.
- Opioid (or opiate) pain relievers.
Opioid-type pain relievers are derived from morphine and are among the most potent pain relievers.
Unfortunately, if used for long treatments, or in excessive doses, they can be very dangerous.
The opioid-type pain reliever most used in the presence of neuropathic pain is tramadol.
Since the latter acts differently from antidepressants and antiepileptics, it can be taken, only on the doctor's prescription, in combination with these medicines.
Main side effects of tramadol: addiction, nausea, vomiting, excessive sweating and constipation.
- Capsaicin in cream.
Capsaicin is a chemical compound found in hot pepper plants, which somehow manages to stop the pain signal sent by the nerves to the brain.
The capsaicin cream should be spread 3 to 4 times a day on the area of the suffering body; to appreciate the results, you have to wait about 10 days.
Doctors advise against its application in case of inflamed or wounded skin.
Main side effects of capsaicin cream: skin irritation and / or burning, especially if not used regularly.
- Other drugs.
According to what has emerged from some clinical cases, injections of ketamine and lidocaine gel seem to have positive effects on neuropathic pain. Ketamine and lidocaine are both generally used as anesthetic drugs.
For doctors, the thorniest problem in prescribing the aforementioned drugs (particularly antidepressants, anticonvulsants and pain relievers) lies in quantifying the most appropriate dose. In this case, the most appropriate dose means the minimum amount of effective drug. Moreover, as already stated, excessive or prolonged doses of a drug such as tramadol can lead to unpleasant side effects.
For the choice of the most suitable dose, we generally proceed by trial and error, as each individual represents a case in itself.
PHYSICAL OR NON-PHARMACOLOGICAL TREATMENTS
There is a series of different non-pharmacological treatments, which can also be defined as physical treatments, which are able to determine a more or less evident improvement in the symptomatological picture, depending on the severity of the neuropathic pain.
Physiotherapy, PENS (Percutaneous Electrical Nervous Stimulation) and TENS (Transcutaneous Electrical Nerve Stimulation) belong to this category of physical treatments.
PENS and TENS, on the other hand, are two medical techniques, which involve the infusion of some electrical discharges in order to reduce the transmission of painful signals, therefore also the sensation of neuropathic pain. The electrical discharges are imparted by electrodes; electrodes can be needles to be inserted through the skin (as in the case of PENS) or patch-like plates to be applied to the skin (as in the case of TENS).
PSYCHOLOGICAL TREATMENT
According to various scientific studies, anxiety, stress and depression induced by a poor state of health, or by other situations in life, contribute to the worsening of neuropathic pain.
Therefore, doctors find it useful, in some cases, to also resort to a targeted psychological treatment, through which the patient is taught how to manage the most stressful situations, moments of anxiety and / or depressive crises.
Prognosis
Neuropathic pain generally has a poor prognosis, as peripheral neuropathies and damage to the central nervous system are usually irreversible and untreatable conditions.
In addition to this, then, it must be considered that, although effective, today's symptomatic treatments (in particular pharmacological ones) represent a problem of some importance from the point of view of side effects.
There is therefore a current need for doctors and researchers to develop a treatment method for neuropathic pain that is effective and, at the same time, with a low risk of complications.
