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Neuropathic pain

According to the definition made by the International Association of Pain Studies in 1997, neuropathic pain, is a system whereby the pain is caused by primary lesion or dysfunction.

Although the clinical course may vary according to the area of origin, it begins with a disorder related to pain management in the central and peripheral nervous system and develops as a secondary to this disor. However, in many patients with neuropathic pain, there is no pathological finding in the central nervous system, and neuropathic pain can not be observed in many patients with nervous system pathology.


Neuropathic pain, a chronic type of pain, can last for months or years after the onset of the disease.



Neuropathic pain can be classified as central or peripheral neuropathic pain according to the origin. The autonomic nervous system also affects neuropathic pain. Such neuropathic pain is defined as Complex Regional Pain Syndromes.


In the etiology of peripheral neuropathic pain, peripheral nerve damage plays a role in different causes.


Factors that play a role in this damage:


  • .Focal nerve damage

  • Trauma (crushing, avulsion, incision, stretching)

  • Tumor (neuroma)

  • Infection (postherpetic neuralgia)

  • Ischemia

  • Jamming

  • Damage (hot, cold, electricity, radiation)

  • Generic nerve damage

  • toxins

  • Metabolic effects (Diabetes mellitus)

  • Schwann cell damage

  • Nutritional disorders (Vit B12 deficiency)

  • Multiple sclerosis

  • Guillaine Barre syndrome



The incidence of neuropathic pain in the general population is 1-2%. However, this incidence may be higher in some patient For example, in 8% of stroke patients, central venous pancreatic pain may develop within 1 year, while 10-15% of patients with HIV infection develop neuropathic pain. In patients with multiple sclerosis, moderate-to-severe pain was reported in 22% of cases.


After acute herpes zoster infection, 20% deafferentation pain can develop especially in patients over 60 years of age. This ratio reaches 34% over 80 years old.


In diabetic patients, neuropathic pain is seen in 50%, especially if the disease lasts for more than 25 years.

The pathophysiology of neuropathic pain is not well understood. As a matter of fact, experimental studies related to nontraumatic neuropathic pain are few. However, it is thought that peripheral and central sensitization mainly play a role in the pathogenesis of chronic neuropathic pain.


The inflammatory and growth factors released after a peripheral nerve injury are released.

As a consequence, nociceptive neurotransmitters such as substance P and brain-derived neurotrophic factor (BDNF) are emerging.


Adrenergic, TrpV1, P2X and m o receptors associated with these released neurotransmitters and Ad and C fibers affect the sodium and calcium channels. The resulting ectopic discharges are caused by peripheral sensitization. Ab fibers also play a role, especially in the process of mechanical allodynia.


Central sensitization, neuropathic pain persistence and painless stimuli are the causes of posttraumatic pain.

 Factors that play a role in this sensitization in the spinal cord:

• Increased upregulation of N-methyl-D-aspartate (NMDA)

• Calcium ion changes in the cell

• Decrease in inhibitor control


Although the underlying mechanisms are not fully understood, it is thought that C fiber sensitization, partial denervation, ectopic activity, endogenous nerve growth factor (NGF) and damaged and undamaged neurons play a role in pathogenesis in the development of neuropathic pain. A symptom can occur through several mechanisms (peripheral and central sensitization in the allodynia of the touch) and multiple mechanisms in the pathogenesis of a syndrome (postherpetic neuralgia).




Whether or not there is an abnormal feeling in the history should be questioned. Hyperalgesia, dysesthesia, allodynia, hyperpathy, hyperesthesia and persistent burning may be the pain types. It should be known whether infection, metabolic disorders, autoimmune diseases and malignancy are present in the underlying pathology. The severity of pain should be assessed and paroxysmal attacks of pain should be asked. The quality of life, emotional and psychological status of the patient should also be assessed. Sleep disturbances and physical restraints are also parameters to be emphasized in the history. Treatments the patient has already received and their response should be known.



 In patients with neuropathic pain clinically symptoms are manifested by persisting pain. Pain may occasionally show paroxysmal course. The character may be of a flammable or sinking nature or of a flammable nature. Abnormal feelings after stimulation, sleep disturbances, emotional and psychological disturbances, physical restraints and autonomic symptoms may accompany the pain. Pain may not always be localized, but in some patients it may be anatomically symptomatic in the appropriate region.

Abnormal sensation manifests itself as hyperalgesia or allodyni. Hyperalgesia is defined as painful stimulation with increased pain response. It can be classified as mechanical, thermal or chemical hyperalgesia. Whereas allodynia is a pain response given to a painless stimulus. It is classified as dynamic and cold allody

Physical examination:

Determining the boundaries of the affected area of the patient also leads to monitoring during treatment. Examination of the superficial nerve is carried out with cotton, brush sheath, thread, needle penetration and tactile to understand the presence of abnomal sensation. Skin temperature measurement can give insight into the autonomic change. Edema, colour change, sweating disorder, atrophy of the skin and nail changes are important in the evaluation of sympathetic pain. Assessment of tactile and vibration thresholds is an auxiliary parameter in both diagnosis and follow-up.

Advanced examinations:

Quantitative Sensory Test (QST) is an important test in the follow-up of treatment by determining baseline value. Magnetic Resonance Examination (MRI) and electromyography can be performed to determine the location of the nerve lesion.

Positron Emission Tomography (PET) and Functional MRI (fMRI) are promising methods in terms of clarifying the mechanisms of neuropathic pain and directing treatment. 



Postherpetic Neuralgia: 


Post herpetic neuralgia (PHN) develops in about 10% of the herpes zoster cases.

The rate is higher in old people. Diabetes mellitus is a predisposing factor for herpes zoster and increases the likelihood of developing postherpetic neuralgia.If the pain persists for 4-6 weeks after the dermatomal vesicles heal, a PHN diagnosis is made. PHN pain is a persistent, inflammatory, irritating pain and sometimes knife like stabbing. Starting spontaneous or triggered by slight stimulation of the skin. On skin, is usually hyperesthesia and hyperalgesia but rarely analgesia.  Frequent dysesthesia and paresthesia may accompany. PHN can be very prolonged especially in patients over 60 years of age. 


Diabetic Neuropathy:

The most common cause of neuropathic pain is diabetic neurop. Different mechanisms play a role in the development of diabetic neuropathy. It is about the "sorbitol route", which is mostly rinsed and studied. Glucose is converted to sorbitol by the aldose reductase enzyme. Overgrowth of this pathway due to hyperglycemia leads to accumulation of sorbitol in the cell. This accumulation leads to myoinositol and taurine depletion in the cell, which eventually degrades cell metabolism.

The reduction of taurine and myoinositol in the cell has been reported to lead to a decrease in Na + -K + ATPase activity and a decrease in the rate of neurotransmission. The second mechanism is decreased endoneural blood flow and nerve ischemia. Reduced nerve blood flow leads to reduced nerve conduction velocity. Disorders related to neurotrophic factors have been found in findings that may be responsible for diabetic neuropathy. The views on the role of autoimmune mechanisms in the development of diabetic neuropathy have begun to gain importance in recent years. There are many studies showing the presence of microscopic vasculitis in nerve biopsies of patients with diabetic lumbosacral radiculopopathy. These findings have led to the application of immunodomalytic therapies, including intravenous immunoglobulin in the anterior segment, in the treatment of diabetic neuropathy. Diabetic neuropathy is clinically characterized as mononeuropathy or polyneuropathy. It is often seen in the third cranial nerve neuropathy. Ayrıca median ulnar, peroneal, femoral ve lateral kutanöz sinirler de tutulur. Pain is expressed by the patient as throbbing, burning, cramping and pain in distal areas.


Sensory symmetric polyneuropathy is seen in 35% of diabetic patients. In addition, burning pain complaint may be accompanied by drowsiness, paresthesia, and autonomic dysfunction.

Fantom Extreme Pain:

 Phantom extremity pain (FEA) is defined as pain following surgical or traumatic amputation.

Pain may be accompanied by sensory disturbances, paresthesia, dysesthesia, hyperpathy.

Phantom pain may occur in the first week after amputation by 50-75%, or in some cases after a few months or years. It is suggested that the preamputation pain is the root of phantom extremity pain. But this relationship is not clear. Post-amputation factors also play a role in FEA.

The severity of the pain varies from patient to patient. Severe pain usually accompanies paresthesia. It can be continuous and periodical. Pain quality is also very variable. It is described as flammable, cramp-like and acutely painful. Pain is localized to the phantom (not available) distal to the limb (hands and feet). The stump pain usually has a palpable neuroma in the incision area.


Emotional touch and pressure, emotional tension, air change, autonomic and reflex movements, stimulation of other body regions may increase pain. Rest, cold or hot application and prosthetic application can lift the pain from the middle. Phantom pain usually declines gradually and disappears within 1-2 years.



Neuropathic pain management approach to other painful syndromes approach is not established. 

There are differences in etiological factors and mechanisms, as well as differences in the approach to neuropathic pain in different disciplines

Targets in the treatment of neuropathic pain:


• Reduction of pain intensity

• Reduction of painful surface area

• The pain must be a change of character and quality.

Various treatment approaches have been proposed to achieve this goal.

 Transcutaneous Electrical Nerve Stimulation (TENS):

In the treatment of neuropathic pain, TENS is a low-grade treatment modality that may be effective in some cases and has a potential side effect, although there is less evidence than other treatment approaches. Positive results have been reported with high and low frequency warning techniques in neuropathic pain.


Neural Blocks:

The efficacy of neural blocks with local anesthetic or neurolytic agents was not studied in randomized placebo controlled trials. The mechanism of action of such interventions envisages blockage of delivery of painful impulses from the periphery. It is suggested that this blockage reduces pain by reducing neurotransmitter release and sensitization


Some neuropathic pain syndromes in which neural blocks can be applied:

• Postherpetic neuralgia has been reported to reduce pain with recurrent stellar ganglion blockade.

. Neuropathic pain in peripheral vascular ischemic diseases can reduce pain and allodynia with neurolytic lumbar sympathetic block.

• Severe persistent pain can be relieved by ablation of the trigeminal neuralgia ganglion.

• In the case of complex regional pain syndrome, intravenous blotting with guanethidine and ketanserin has been reported to relieve pain. There is an opinion that the pressure applied on the nerve by the turniken used in this method may also contribute to the pain palliation.

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