Generality
Neuropathic pain, or neuralgia, is a chronic painful sensation that appears following a deterioration, or a malfunction, of the nerves of the peripheral nervous system (peripheral neuropathy) or of the structures of the central nervous system.
The causes of this condition are numerous. These include nerve compression, some infectious diseases, diabetes and multiple sclerosis.
The therapy is based on treating the triggers and treating the symptoms.
Brief reference to the nervous system
The nervous system is a collection 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 elaboration, the nervous system generates appropriate responses to the situation, which favor the survival of the organism to which it belongs.
The nervous system of vertebrates consists of two components:
- The central nervous system ( CNS ): is the most important part of the nervous system, a veritable data processing and control center. In fact, it analyzes the information coming from the external and internal environment of the organism, therefore it formulates the most appropriate answers to the aforementioned information.
It is composed of 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 informative data captured inside and outside the organism and in spreading all processing with origin in the CNS towards the periphery.
Without the SNP, 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 occurs due to damage or malfunction of the nerves of the peripheral nervous system or of the structures constituting the central nervous system.
The neuropathic adjective and the related terms (eg neuropathy) derive from the union of two words: "neuro", which refers to the nerves, and "patico" (or "patia"), 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 (nervous) signals, which allow muscular movement, sensory perceptions, reflex responses and so on.
Typically, one neuron consists of three parts:
- A body or soma, where the cell nucleus resides;
- Dendrites, which are equivalent to receiving antennas of nerve signals generally coming from other neurons;
- Axons, which are extensions that act as diffusers of the nervous signal. They may or may not be wrapped in a whitish substance, called myelin (myelin coating sheath).
An axon covered by its myelin coating is also called nerve fiber .
A nerve fiber is not a nerve: a nerve is a bundle of axons .
Thus, in light of this, a set of nerve fibers can constitute a nerve.
Based on 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, ie from the central nervous system to the periphery.
CENTRAL AND PERIPHERAL NEUROPATHIC PAIN
If the damage or malfunction affects the encephalon and / or spinal cord (thus the main structures of the central nervous system), it is called central neuropathic pain .
On the contrary, if the lesion or dysfunction affects one or more nerves of the peripheral nervous system, it is called peripheral neuropathic pain . In such situations, the condition that induces peripheral neuropathic pain is called peripheral neuropathy .
DIFFERENCES FROM NOCICETTIVE PAIN
Neuropathic pain is different from the painful sensation that is experienced following a wound, a burn, a trauma or a strong pressure (such as that exerted by a tumor that pushes on the 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, is a disorder that is easier to interpret, in terms of causes, and above all to be cured.
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 without an identifiable reason - in this case we also speak of idiopathic neuropathic pain - or due to very specific conditions, morbid and not morbid, such as:
- Compression of a nerve (or nerve compression ). Blood vessel abnormalities (eg microaneurysms), ligaments, expanding tumor masses or bones can compress (or crush) a nearby nerve. Its crushing can cause erosion of the myelin sheath of its axons, which causes a loss of function by the same nerve and a feeling of neuropathic pain.
They are the result of a nervous 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 with involvement of the nervous system . Some viruses and bacteria are able to invade and damage nerve cells, including those that make up nerves.
Among the most well-known infections that can cause neuropathic pain, are herpes zoster (NB: in these cases one also speaks of post-herpetic neuralgia), AIDS, Lyme disease and syphilis.
- Diabetic neuropathy . High blood glucose levels (hyperglycaemia), typical of people with diabetes, damage the blood vessels that supply the nerves of the SNP with oxygen and nutrients. In the absence of oxygen and nutrients, any nerve, tissue or organ in the body undergoes necrosis, or death.
Diabetes represents one of the main causes of peripheral neuropathy in Western world countries, such as Italy or the United Kingdom.
- Multiple sclerosis . It is a chronic and debilitating disease that occurs due to the progressive degradation of myelin belonging to the neurons of the central nervous system. Therefore, the resulting neuropathic pain is the result of central neuropathy.
- Phantom limb syndrome . It is a particular morbid condition, characterized by the anomalous sensation of persistence of a limb, despite the amputation of the latter.
Those who suffer from it, therefore, are people who, for some reason, have had a part of the body amputated (a foot, a hand, etc.).
Patients with this problem claim to still feel the missing limb and to feel a constant pain at its expense.
- Vitamin deficiencies induced by alcoholism or other situations of malnutrition . Vitamins (in particular B12, B1, B6, niacin and E) are fundamental for the good health of the nervous system, therefore their deficiency entails, among the various consequences, also the deterioration of the nerves of the peripheral nervous system and neurons of the central nervous system.
- Trauma to the spine or peripheral nerves . A trauma of a certain relevance can irreparably damage an important nerve organ such as the spinal cord or the nerves of the peripheral nervous system. Thus traumatic neuropathic pain can be both central and peripheral.
Very serious traumatic events are those that can occur during a spine surgery, a fall, a car accident or a bone fracture.
- A chemotherapy treatment for the treatment of a tumor . Some highly used chemotherapy drugs, including cisplatin, vincristine and paclitaxel, can cause a form of peripheral neuropathy, hence neuropathic pain.
- Prolonged exposure to toxic substances . They can cause neuropathic pain, due to a situation of peripheral neuropathy, substances such as arsenic, insecticides, lead or mercury.
- The porphyrias . They are a group of diseases, almost always of hereditary type, due to a functional alteration of one of the enzymes that synthesize the so-called EME group. The heme group is a non-protein molecule, which is a fundamental part of some proteins, including blood hemoglobin, myoglobin and cytochromes.
- Chronic kidney diseases . If the kidneys are malfunctioning, there is an accumulation of toxic substances in the body; these toxic substances are harmful to the nerves of the peripheral nervous system.
Epidemiology
Figure: alcoholism is a possible cause of peripheral neuropathy, which, in turn, is a cause of neuropathic pain.
According to statistical research, in the United States neuropathic pain would affect between 3 and 8% of the population, while in the United Kingdom it would affect about 7% of the inhabitants.
Older people suffer the most (NB: this applies to most countries of the world) who suffer from the aforementioned morbid conditions, responsible for neuropathies.
Symptoms and Complications
Usually, patients with neuropathic pain experience excruciating and / or burning painful sensations .
Moreover, in association, they develop a particular sensitivity to painful stimuli and complain of tingling and numbness in the suffering area (generally the extremities of the upper limbs and lower limbs).
PARTICULAR SENSITIVITY? IN PAIN: ALLODYIA AND HYPERALGESIA
Sufferers of neuropathic pain often manifest allodynia and / or hyperalgesia .
In medicine, these two terms identify exaggerated responses to painful stimuli.
To be precise, we talk about allodynia when we feel pain even after 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 are the cause of marked suffering.
COMPLICATIONS
If adequate treatment is not applied, the symptoms of neuropathic pain can become increasingly intense and increasingly difficult to treat.
Diagnosis
The diagnosis of neuropathic pain is generally based on a thorough physical examination (during which the doctor evaluates the patient's symptoms and clinical history ), a neurological evaluation, blood tests and an electromyography .
The use of further tests - such as for example CT, MRI and nerve biopsy - takes place in particular cases (for example if a tumor is suspected) and to gather further information.
The final aim 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 : first the diagnosis occurs (early diagnosis), the smaller the amount of neuropathic pain and the consequences of damage to the nervous level.
EXAMINATION OBJECTIVE
During the physical examination, the doctor asks the patient to describe in detail the type of pain felt. In addition, he questions him about the illnesses he suffered in the past, current illnesses, work activity and drugs in use.
Treatment
Neuropathic pain therapy includes:
- The specific treatment of the triggering factor damages the nervous system (central or peripheral).
- Pharmacological treatment of neuropathic pain itself.
- Various physical (or non-pharmacological) treatments of symptoms.
- A psychological treatment
TREATMENT OF THE TRAINING CAUSES
Although it is only in some cases resolving the problem, treating the cause of the onset of neuropathic pain is very important, because it can strongly slow down (or even 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 agents), keep blood pressure controlled and regulate body weight.
Treating the triggering causes does not mean re-establishing the conditions preceding 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 an early diagnosis.
PHARMACOLOGICAL TREATMENT
The most well-known and used pain-relieving and anti-inflammatory drugs, such as paracetamol or ibuprofen, are poorly effective against neuropathic pain.
More powerful and different kinds of medicines are needed.
In particular, doctors use:
- Antidepressants of the tricyclic group and of the serotonin and noradrenaline reuptake inhibitor group .
Although it may seem strange, these drugs for treating depression also relieve symptoms associated with neuropathic pain with some success.
Of the group of tricyclics, amitriptyline, doxepin and nortriptyline are mentioned . 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.
Main side effects of tricyclics: drowsiness, 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 given in case of epilepsy.
Among these pharmacological preparations, those effective against neuropathic pain are gabapentin and pregabalin .
Usually prescribed as an alternative to antidepressants (NB: 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-type painkillers (or opiates) .
Opioid-type painkillers are derived from morphine and are among the most powerful pain medications.
Unfortunately, if used for long treatments, or in excessive doses, they can be very dangerous.
The most widely used opioid-type painkiller in the presence of neuropathic pain is tramadol .
Since the latter acts differently from antidepressants and antiepileptics, it can be taken, exclusively 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 painful signal sent from nerves to the brain.
Capsaicin in 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 application in case of inflamed or wounded skin.
Main side effects of capsaicin in cream: irritation and / or burning in the skin, especially if it is not used regularly.
- Other drugs .
According to some clinical cases, ketamine injections and gel lidocaine seem to have positive effects on neuropathic pain. Ketamine and lidocaine are generally both used as anesthetic drugs.
For doctors, the thorniest problem in prescribing the aforementioned drugs (in particular antidepressants, anticonvulsants and painkillers) lies in the quantification of the most appropriate dose . By the most appropriate dose is meant, in this case, the minimum amount of effective drug. Moreover, as already stated, excessive or prolonged doses of a medicine such as tramadol can have unpleasant side effects.
To choose the most appropriate 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 an improvement in the symptomatology more or less evident, depending on the severity of neuropathic pain.
To this category of physical treatments belong: physiotherapy, PENS (Electric Percutaneous Nerve Stimulation) and TENS (Transcutaneous Nerve Electrical Stimulation).
PENS and TENS, on the other hand, are two medical techniques, which provide for the infusion of some electric shocks in order to reduce the transmission of painful signals, and therefore also the sensation of neuropathic pain. Electric discharges are given by electrodes; these electrodes can be needles to be inserted through the skin (as in the case of PENS) or patch-like plaques to be applied to the skin (as in the case of TENS).
PSYCHOLOGICAL TREATMENT
According to several scientific studies, anxiety, stress and depression induced by a sub-optimal state of health, or by other life situations, contribute to the worsening of neuropathic pain.
Therefore, doctors believe it is 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 depression.
Prognosis
Neuropathic pain generally has a non-positive prognosis, as peripheral neuropathies and damage to the central nervous system are usually irreversible conditions from which it cannot be cured.
In addition to this, then, it must be considered that, although effective, today's symptomatic treatments (particularly pharmacological ones) represent a problem of a certain relevance from the point of view of the side effects.
It is therefore current the need for doctors and researchers to develop a treatment method for effective neuropathic pain and, at the same time, low risk complications.
