<unk>  can be very difficult to treat with only some 40-60% of people achieving partial relief. General approach First line treatments are certain antidepressants (tricyclic antidepressants and serotonin–norepinephrine reuptake inhibitors), anticonvulsants (pregabalin and gabapentin). Opioid analgesics are recognized as useful agents but are not recommended as first line treatments. A broader range of treatments are used in specialist care. There are limited data and guidance for the long-term treatment of<unk> . Notably, strong evidence from randomized controlled trials is not available for all interventions. Primary interventions Anticonvulsants Pregabalin and gabapentin may reduce<unk>  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 depolarisation. 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<unk>  or fibromyalgia in some people. There is no predictor test to determine if it will be effective for a particular person. A short trial period of gabapentin therapy is recommended, to determine the effectiveness for that person. 62% of people taking gabapentin may have at least one adverse event, however the incidence of serious adverse events was found to be low. Although gabapentin and pregabalin possess low abuse potential, these drugs can cause physical dependence over the course of normal treatment, and certain patients may become psychologically dependent as well. Meta analysis of randomized clinical trials suggests that Lamotrigine is not useful for the majority of patients although it may have use in treatment 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 Opioids, while commonly used in chronic<unk> , are not a recommended first or second line treatment. In the short and long term they are of unclear benefit, although clinical experience suggests that opioids like tramadol may be useful for treating sudden onset severe<unk>  In the intermediate term evidence of low quality 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 analgesic in experimental models of chronic<unk> . There is little evidence to indicate that one strong opioid is more effective than another. Expert opinion leans toward the use of methadone for<unk> , 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<unk>  relief to people with<unk> . The potential<unk>  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<unk> . Importantly, recent observational studies suggest a<unk> -relief benefit in non-cancer related chronic<unk>  of reducing or terminating long-term opioid therapy. Non-Pharmaceutical Interventions Non-pharmaceutical treatments such as exercise, physical therapy and psychotherapy may be useful adjuncts to treatment. Secondary and research interventions Botulinum toxin type A Local intradermal injection of botulinum neurotoxin type A may be helpful in chronic focal<unk> ful<unk> s. However, it causes muscle paralysis which may impact quality of life. Cannabinoids Evidence for the use of Cannabis based medicines is limited, low-moderate quality evidence suggests a benefit in<unk>  intensity, sleep quality and psychological distress. The use of Cannabis has to be weighed against the negative psychotomimetic effects that may impact quality of life. Therefore, cannabis is not recommended as a mainstream treatment but may have a place for treatment refractory cases. Neuromodulators Neuromodulation is a field of science, medicine and bioengineering that encompasses both implantable and non-implantable technologies (electrical and chemical) for treatment purposes. Implanted devices are expensive and carry the risk of complications. Available studies have focused on conditions having a different prevalence than<unk>  patients in general. More research is needed to define the range of conditions that they might benefit. Deep brain stimulation The best long-term results with deep brain stimulation have been reported with targets in the periventricular/periaqueductal grey matter (79%), or the periventricular/periaqueductal grey matter plus thalamus and/or internal capsule (87%). There is a significant complication rate, which increases over time. Motor cortex stimulation Stimulation of the primary motor cortex through electrodes placed within the skull but outside the thick meningeal membrane (dura) has been used to treat<unk> . The level of stimulation is below that for motor stimulation. As compared with spinal stimulation, which is associated with noticeable tingling (paresthesia) at treatment levels, the only palpable effect is<unk>  relief. Spinal cord stimulators implanted spinal pumps Spinal cord stimulators use electrodes placed adjacent to but outside the spinal cord. The overall complication rate is one-third, most commonly due to lead migration or breakage but advancements in the past decade have driven complication rates much lower. Lack of<unk>  relief occasionally prompts device removal. NMDA antagonism The N-methyl-D-aspartate (NMDA) receptor seems to play a major role in<unk>  and in the development of opioid tolerance. Dextromethorphan is an NMDA antagonist at high doses. Experiments in both animals and humans have established that NMDA antagonists such as ketamine and dextromethorphan can alleviate<unk>  and reverse opioid tolerance. Unfortunately, only a few NMDA antagonists are clinically available and their use is limited by a very short half life (ketamine), weak activity (memantine) or unacceptable side effects (dextromethorpan). Intrathecal drug delivery Intrathecal pumps deliver medication to the fluid filled (subarachnoid) space surrounding the spinal cord. Opioids alone or opioids with adjunctive medication (either a local anesthetic or clonidine) Rarely there are complications such as serious infection (meningitis), urinary retention, hormonal disturbance and intrathecal granuloma formation have been noted with intrathecal infusion, associated with the delivery method. Conotoxins Ziconotide is a voltage-gated calcium channel blocker which may be used in severe cases of ongoing<unk>  it is delivered intrathecally. Topical agents In some forms of neuropathy the topical application of local anesthetics such as lidocaine may provide relief. A transdermal patch containing lidocaine is available commercially in some countries. Repeated topical applications of capsaicin are followed by a prolonged period of reduced skin sensibility referred to as desensitization, or nociceptor inactivation. Capsaicin causes reversible degeneration of epidermal nerve fibers. Notably the capsaicin used for the relief of<unk>  is a substantially higher concentration than capsaicin creams available over the counter, there is no evidence that over the counter capsaicin cream can improve<unk>  and topical capsaicin can itself induce<unk> . Surgical Interventions Orthopaedic interventions are frequently used to correct underlying pathology which may contribute to<unk> . Many orthopaedic procedures have more limited evidence. Historically, neurosurgeons have attempted lesions of regions of the brain, spinal cord and peripheral nervous system. Whilst they cause some short term analgesia, these are considered to be universally ineffective. Alternative therapies Herbal products There is no good evidence that herbal products (nutmeg or St John's wort) are useful for treating<unk> . Dietary supplements A 2007 review of studies found that injected (parenteral) administration of alpha lipoic acid (ALA) was found to reduce the various symptoms of peripheral diabetic neuropathy. While some studies on orally administered ALA had suggested a reduction in both the positive symptoms of diabetic neuropathy (dysesthesia including stabbing and burning<unk>  as well as<unk>  deficits (paresthesia), the meta-analysis showed "more conflicting data whether it improves sensory symptoms or just<unk>  deficits alone". There is some limited evidence that ALA is also helpful in some other non-diabetic<unk> s. Benfotiamine is an oral prodrug of Vitamin B1 that has several placebo-controlled double-blind trials proving efficacy in treating neuropathy and various other diabetic comorbidities.
Neuropathic pain
Cancer
Phantom pain
Psychogenic pain
Nociplastic pain
Hyperalgesia
Allodynia
Chromesthesia