Neuropathic pain
Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli. It may have continuous and/or episodic components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, "pins and needles" sensations, numbness and itching.
Up to 7–8% of the European population is affected by neuropathic pain, and in 5% of persons it may be severe. The pain may result from disorders of the peripheral nervous system or the central nervous system. Neuropathic pain may occur in isolation or in combination with other forms of pain. Medical treatments focus on identifying the underlying cause and relieving pain. In cases of peripheral neuropathy, the pain may progress to insensitivity.
Diagnosis
Diagnosis of pain conditions relies on the character of the pain with a sharp stabbing character and the presence of particular features such as mechanical allodynia and cold allodynia. Neuropathic pain also tends to affect defined dermatomes and there may be limits to the area of pain. For neuropathic pain, clinicians look for an underlying lesion to the nervous system or an inciting cause consistent with the development of neuropathic pain. The obvious presence of an underlying feature or cause is not always detectable, and response to treatment may be used as a surrogate particularly in cases where diagnosis of the underlying lesion leaves the patient in pain for a prolonged period of time. MRI may be helpful in the identification of underlying lesions, reversible causes or serious underlying conditions such as primary presentation of a tumor or multiple sclerosis. Quantitative sensory testing, a system of detailed analysis of the somatosensory system, is frequently used in research situations to identify neuropathic pain and a more detailed analysis of its components. It has been suggested by some authorities that QST may have a future role in the diagnosis of neuropathic pain and in particular the identification of neuropathic pain subtypes. Neuropathic pain can occur alone or in combination with other types of pain. The identification of neuropathic pain components is important as different classes of analgesic are required.The gold standard for diagnosing small fiber neuropathy as the etiology of neuropathic pain is skin biopsy. Sudomotor assessment, through electrochemical skin conductance, an accurate objective technique, could be considered as a good screening tool to limit skin biopsy in patients in whom it is not suitable.
Causes
Neuropathic pain may be divided into peripheral, central or mixed types. Central neuropathic pain is found in spinal cord injury and multiple sclerosis. Peripheral neuropathies are commonly caused by diabetes, metabolic disorders, herpes zoster infection, HIV-related neuropathies, nutritional deficiencies, toxins, remote manifestations of malignancies, immune mediated disorders and physical trauma to a nerve trunk. Neuropathic pain is common in cancer as a direct result of cancer on peripheral nerves, or as an adverse effect of chemotherapy or radiotherapy, radiation injury or surgery.Comorbidities
Neuropathic pain has profound physiological effects on the brain, which can manifest as psychological disorders. Rodent models in which the social effects of chronic pain can be isolated from other factors suggest that induction of chronic pain can cause anxiety-depressive symptoms and that particular circuits in the brain have a direct connection. Depression and neuropathic pain may have a bidirectional relationship, and relief of co-morbid depression may underlie some of the therapeutic efficacy of antidepressants in neuropathic pain. Neuropathic pain has important effects on social well-being that should not be ignored. People with neuropathic pain may have difficulty working exhibiting higher levels of presenteeism, absenteeism and unemployment, exhibit higher levels of substance misuse, and present difficulties with social interactions. Moreover, uncontrolled neuropathic pain is a significant risk factor for suicide. Certain classes of neuropathic pain may cause serious adverse effects necessitating hospital admission. For instance, trigeminal neuralgia can present as a severe crisis wherein the patient may have difficulty talking, eating, and drinking. As neuropathic pain may be comorbid with cancer, it can have important dose limiting effects on certain classes of chemotherapeutic.Treatments
Neuropathic pain can be very difficult to treat, with only some 40–60% of people achieving partial relief.General approach
First-line treatments include certain antidepressants and anticonvulsants. Opioid analgesics are recognized as useful in some cases but not recommended as first-line treatments. A broader range of treatments is used in specialist care. There is limited data and guidance for the long-term treatment of pain. Notably, strong evidence from randomized controlled trials is not universal for all interventions.Primary interventions
Anticonvulsants
Pregabalin and gabapentin may reduce pain associated with diabetic neuropathy. The anticonvulsants carbamazepine and oxcarbazepine are especially effective in trigeminal neuralgia. Carbamazepine is a voltage-gated sodium channel inhibitor and reduces neuronal excitability by preventing depolarization. Carbamazepine is most commonly prescribed to treat trigeminal neuralgia due to clinical experience and early clinical trials showing strong efficacy. Gabapentin may reduce symptoms associated with neuropathic pain or fibromyalgia in some people. There is no test to predict the effectiveness of gabapentin for individuals, so a short trial is suggested to assess its effectiveness. While 62% of users may experience at least one adverse event, serious adverse events are rare.A meta-analysis of randomized clinical trials suggests that lamotrigine is not useful for most patients, although it may have been used in the treatment of refractory cases.
Antidepressants
Dual serotonin-norepinephrine reuptake inhibitors in particular duloxetine, as well as tricyclic antidepressants in particular amitriptyline, and nortriptyline are considered first-line medications for this condition.Opioids
s, while commonly used in chronic neuropathic pain, are not recommended as first- or second-line treatment. In the short and long term, they are of unclear benefit. However, clinical experience suggests that opioids like tramadol may be useful for treating sudden-onset severe pain. In the intermediate term, low-quality evidence supports utility.Several opioids, particularly levorphanol, methadone, and ketobemidone, possess NMDA receptor antagonism in addition to their μ-opioid agonist properties. Methadone does so because it is a racemic mixture; only the l-isomer is a potent μ-opioid agonist. The d-isomer does not have opioid agonist action and acts as an NMDA receptor antagonist; d-methadone is an analgesic in experimental models of chronic pain.
There is little evidence to indicate that one potent opioid is more effective than another. Expert opinion leans toward the use of methadone for neuropathic pain, in part because of its NMDA antagonism. It is reasonable to base the choice of opioid on other factors. It is unclear if fentanyl gives pain relief to people with neuropathic pain. The potential pain relief benefits of strong opioids must be weighed against their significant addiction potential under normal clinical use, and some authorities suggest that they should be reserved for cancer pain. Importantly, recent observational studies suggest a pain-relief benefit in non-cancer-related chronic pain of reducing or terminating long-term opioid therapy.