Pharmacological techniques are often continued in conjunction with other treatment options. Doses of pain medications needed often drop substantially when combined with other techniques, but rarely are discontinued completely. Tricyclic antidepressants, such as amitriptyline, and sodium channel blockers, mainly carbamazepine, are often used to relieve chronic pain, and recently have been used in an attempt to reduce phantom pains. Pain relief may also be achieved through use of opioids, ketamine, calcitonin, and lidocaine.

Various methods have been used to treat phantom limb pain. Doctors may prescribe medications to reduce the pain. Some antidepressants or antiepileptics have been shown to have a beneficial effect on reducing phantom limb pain. Often physical methods such as light massage, electrical stimulation, and hot and cold therapy have been used with variable results.

There are many different treatment options for phantom limb pain that are actively being researched. Most treatments do not take into account the mechanisms underlying phantom pains, and are therefore ineffective. However, there are a few treatment options that have been shown to alleviate pain in some patients, but these treatment options usually have a success rate less than 30%. It is important to note that this rate of success does not exceed the placebo effect. It is also important to note that because the degree of cortical reorganization is proportional to phantom limb pains, any perturbations to the amputated regions may increase pain perception.

Most approaches to treatment over the past two decades have not shown consistent symptom improvement. Treatment approaches have included medication such as antidepressants, spinal cord stimulation, vibration therapy, acupuncture, hypnosis, and biofeedback. Reliable evidence is lacking on whether any treatment is more effective than the others.

Most treatments are not very effective. Ketamine or morphine may be useful around the time of surgery. Morphine may be helpful for longer periods of time. Evidence for gabapentin is mixed. Perineural catheters that provide local anesthetic agents have poor evidence when placed after surgery in an effort to prevent phantom limb pain.

Tentative evidence supports the use of bisphosphonates, calcitonin, and ketamine. Doing nerve blocks with guanethidine appears to be harmful. Evidence for sympathetic nerve blocks generally is insufficient to support their use. Intramuscular botulinum injections may benefit people with symptoms localized to one extremity.

Ketamine, a dissociative anesthetic, appears promising as a treatment for complex regional pain syndrome. It may be used in low doses if other treatments have not worked. No benefit on either function or depression, however, has been seen.

One approach that has received public interest is the use of a mirror box. The mirror box provides a reflection of the intact hand or limb that allows the patient to "move" the phantom limb, and to unclench it from potentially painful positions.

As of 2011, however, the quality of evidence is low. There is a wide range in the effectiveness of this approach. The potential for a person to benefit from mirror therapy is not predictable and appears to be related to the subjective ability of the patient to internalize the reflection of a complete limb as their own limb. About 40% of people do not benefit from mirror therapy.

The management of low back pain often includes medications for the duration that they are beneficial. With the first episode of low back pain the hope is a complete cure; however, if the problem becomes chronic, the goals may change to pain management and the recovery of as much function as possible. As pain medications are only somewhat effective, expectations regarding their benefit may differ from reality, and this can lead to decreased satisfaction.

The medication typically recommended first are NSAIDs (though not aspirin) or skeletal muscle relaxants and these are enough for most people. Benefits with NSAIDs; however, is often small. High-quality reviews have found acetaminophen (paracetamol) to be no more effective than placebo at improving pain, quality of life, or function. NSAIDs are more effective for acute episodes than acetaminophen; however, they carry a greater risk of side effects including: kidney failure, stomach ulcers and possibly heart problems. Thus, NSAIDs are a second choice to acetaminophen, recommended only when the pain is not handled by the latter. NSAIDs are available in several different classes; there is no evidence to support the use of COX-2 inhibitors over any other class of NSAIDs with respect to benefits. With respect to safety naproxen may be best. Muscle relaxants may be beneficial.

If the pain is still not managed adequately, short term use of opioids such as morphine may be useful. These medications carry a risk of addiction, may have negative interactions with other drugs, and have a greater risk of side effects, including dizziness, nausea, and constipation. The effect of long term use is unknown. Specialist groups advise against general long-term use of opioids for chronic low back pain.

For older people with chronic pain, opioids may be used in those for whom NSAIDs present too great a risk, including those with diabetes, stomach or heart problems. They may also be useful for a select group of people with neuropathic pain.

Antidepressants may be effective for treating chronic pain associated with symptoms of depression, but they have a risk of side effects. Although the antiseizure drugs gabapentin and carbamazepine are sometimes used for chronic low back pain and may relieve sciatic pain, there is insufficient evidence to support their use. Systemic oral steroids have not been shown to be useful in low back pain. Facet joint injections and steroid injections into the discs have not been found to be effective in those with persistent, non-radiating pain; however, they may be considered for those with persistent sciatic pain. Epidural corticosteroid injections provide a slight and questionable short-term improvement in those with sciatica but are of no long term benefit. There are also concerns of potential side effects.

H-wave therapy (HWT) is a form of electrical stimulation that produces a direct, localized effect on the conduction of underlying nerves. The electrical stimulation used in HWT differs from other forms of electrical stimulation such as TENS in terms of its waveform; it is intended to emulate the H waveform found in nerve signals, thus permitting the machine to use less power while attaining greater and deeper penetration of its low-frequency current. The waves used in HWT are distinct from the H-waves that are part of electromyography. It has been used in the treatment of pain related to diabetic neuropathy, muscle sprains, temporomandibular joint disorders, type I complex regional pain syndrome as well as the healing of wounds such as diabetic ulcers. This electroanalgesic modality was originally recommended as an alternative to TENS for dental analgesia. In a 1999 randomized controlled trial involving a mechanical pain model, the analgesic effects of HWT were found to be short-lasting and identical to those provided by TENS therapy. HWT has not been shown effective in reducing pain in cases other than diabetic neuropathy, nor has it been shown effective in reducing edema or swelling, and it has specifically not been shown effective in treating chronic pain due to ischemia.

Transcutaneous acupoint electrical stimulation, or TAES, is a variant of TENS therapy that involves applying cutaneous electrodes at classical Chinese acupoints and stimulating with alternating high- and low-frequency electric current ("dense-disperse"). Acupoint stimulation is as effective as dermatomal stimulation in producing an analgesic-sparing effect after lower abdominal surgery

Individuals with more social support experience less cancer pain, take less pain medication, report less labor pain and are less likely to use epidural anesthesia during childbirth, or suffer from chest pain after coronary artery bypass surgery.

Suggestion can significantly affect pain intensity. About 35% of people report marked relief after receiving a saline injection they believed to be morphine. This placebo effect is more pronounced in people who are prone to anxiety, and so anxiety reduction may account for some of the effect, but it does not account for all of it. Placebos are more effective for intense pain than mild pain; and they produce progressively weaker effects with repeated administration. It is possible for many with chronic pain to become so absorbed in an activity or entertainment that the pain is no longer felt, or is greatly diminished.

Cognitive behavioral therapy (CBT) has been shown effective for improving quality of life in those with chronic pain but the reduction in suffering is modest, and the CBT method was not shown to have any effect on outcome. Acceptance and Commitment Therapy (ACT) may also effective in the treatment of chronic pain.

A number of meta-analyses have found clinical hypnosis to be effective in controlling pain associated with diagnostic and surgical procedures in both adults and children, as well as pain associated with cancer and childbirth. A 2007 review of 13 studies found evidence for the efficacy of hypnosis in the reduction of chronic pain under some conditions, though the number of patients enrolled in the studies was low, raising issues related to the statistical power to detect group differences, and most lacked credible controls for placebo or expectation. The authors concluded that "although the findings provide support for the general applicability of hypnosis in the treatment of chronic pain, considerably more research will be needed to fully determine the effects of hypnosis for different chronic-pain conditions."

Acute pain is usually managed with medications such as analgesics and anesthetics. Caffeine when added to pain medications such as ibuprofen, may provide some additional benefit. Management of chronic pain, however, is more difficult, and may require the coordinated efforts of a pain management team, which typically includes medical practitioners, clinical pharmacists, clinical psychologists, physiotherapists, occupational therapists, physician assistants, and nurse practitioners.

Sugar (sucrose) when taken by mouth reduces pain in newborn babies undergoing some medical procedures (a lancing of the heel, venipuncture, and intramuscular injections). Sugar does not remove pain from circumcision, and it is unknown if sugar reduces pain for other procedures.

Sugar did not affect pain-related electrical activity in the brains of newborns one second after the heel lance procedure. Sweet liquid by mouth moderately reduces the rate and duration of crying caused by immunization injection in children between one and twelve months of age.

If non-pharmacological measures are not effective, medications may be tried.

- Non-steroidal anti-inflammatory drugs (NSAIDs) are typically tried first. NSAIDs have been shown to be more effective than placebo, and are usually more effective than paracetamol (acetaminophen).

- In severe back pain not relieved by NSAIDs or acetaminophen, opioids may be used. However, long-term use of opioids has not been proven to be effective at treating back pain. Opioids have not always been shown to be better than placebo for chronic back pain when the risks and benefits are considered.

- Skeletal muscle relaxers may also be used. Their short term use has been shown to be effective in the relief of acute back pain. However, the evidence of this effect has been disputed, and these medications do have negative side-effects.

- In people with nerve root pain and acute radiculopathy, there is evidence that a single dose of steroids, such as dexamethasone, may provide pain relief.

- Epidural corticosteroid injection (ESI) is a procedure in which steroid medications are injected into the epidural space. The steroid medications reduce inflammation and thus decrease pain and improve function. ESI has long been used to both diagnose and treat back pain, although recent studies have shown a lack of efficacy in treating low back pain.

Increasing general physical activity has been recommended, but no clear relationship to pain or disability has been found when used for the treatment of an acute episode of pain. For acute pain, low- to moderate-quality evidence supports walking. Treatment according to McKenzie method is somewhat effective for recurrent acute low back pain, but its benefit in the short term does not appear significant. There is tentative evidence to support the use of heat therapy for acute and sub-chronic low back pain but little evidence for the use of either heat or cold therapy in chronic pain. Weak evidence suggests that back belts might decrease the number of missed workdays, but there is nothing to suggest that they will help with the pain. Ultrasound and shock wave therapies do not appear effective and therefore are not recommended.

Exercise therapy is effective in decreasing pain and improving function for those with chronic low back pain. It also appears to reduce recurrence rates for as long as six months after the completion of program and improves long-term function. There is no evidence that one particular type of exercise therapy is more effective than another. The Alexander technique appears useful for chronic back pain, and there is tentative evidence to support the use of yoga. Transcutaneous electrical nerve stimulation (TENS) has not been found to be effective in chronic low back pain. Evidence for the use of shoe insoles as a treatment is inconclusive. Peripheral nerve stimulation, a minimally-invasive procedure, may be useful in cases of chronic low back pain that do not respond to other measures, although the evidence supporting it is not conclusive, and it is not effective for pain that radiates into the leg.

The use of medications to treat acute, chronic, recurrent and neuropathic pain is most common. Most instances of pain in children are treated with analgesics. These include acetaminophen, NSAIDs, local anesthetics, opioids, and medications for neuropathic pain. The most effective approach to pain management in children is to provide medicine around the clock instead of providing pain relief as needed. Regional anesthesia is also effective and recommended whenever possible. Opioids are effective too but often depress breathing in infants.

Chronic pain is treated with a variety of medications and non-pharmacological interventions. Opioid tolerance and withdrawal can be seen in the NICU and PICU. Other side effects with opioid use can be: cognition deficits, altered mood, and disturbances of endocrine development. Opioid misuse can occur in adolescents and is associated with the use of alcohol, cigarettes and marijuana.

Non-pharmacological treatment for children in helping to relieve periodic pain episodes and severity includes counselling and behavior modification therapy. The American Association of Pediatrics have suggested that parents be educated on providing round the clock medication administration after their children receive surgery.

Treatment of people believed to have ATN or TN is usually begun with medication. The long-time first drug of choice for facial neuralgia has been carbamazepine, an anti-seizure agent. Due to the significant side-effects and hazards of this drug, others have recently come into common use as alternatives. These include oxcarbazepine, lamotrigine, and gabapentin. A positive patient response to one of these medications might be considered as supporting evidence for the diagnosis, which is otherwise made from medical history and pain presentation. There are no present medical tests to conclusively confirm TN or ATN.

If the anti-seizure drugs are found ineffective, one of the tricyclic antidepressant medications such as amitriptyline or nortriptyline, may be used. The tricyclic antidepressants are known to have dual action against both depression and neuropathic pain. Other drugs which may also be tried, either individually or in combination with an anti-seizure agent, include baclofen, pregabalin, anti-seizure drugs (to calm nerve endings), muscle relaxants, and opioid drugs such as oxycodone or an oxycodone/paracetamol combination.

For some people with ATN opioids may represent the only viable medical option which preserves quality of life and personal functioning. Although there is considerable controversy in public policy and practice in this branch of medicine, practice guidelines have long been available and published.

The evidence for surgical therapy is poor. Surgery is normally recommended only after medication has proved ineffective, or if side effects of medication are intolerable. While there may be pain relief after surgery, there is also a considerable risk of side effects, such as facial numbness after the procedure. Microvascular decompression appears to result in the longest pain relief. Percutaneous radiofrequency thermorhizotomy may also be effective as may stereotactic radiosurgery; however the effectiveness decreases with time.

Surgical procedures can be separated into non-destructive and destructive:

Many chemical medications have been used for a broad range of neuropathic pain including Dejerine–Roussy syndrome. Symptoms are generally not treatable with ordinary analgesics. Traditional chemicals include opiates and anti-depressants. Newer pharmaceuticals include anti-convulsants and Kampo medicine. Pain treatments are most commonly administered via oral medication or periodic injections. Topical In addition, physical therapy has traditionally been used alongside a medication regimen. More recently, electrical stimulation of the brain and spinal cord and caloric stimulation have been explored as treatments.

The most common treatment plans involve a schedule of physical therapy with a medication regimen. Because the pain is mostly unchanging after development, many patients test different medications and eventually choose the regimen that best adapts to their lifestyle, the most common of which are orally and intravenously administered.

Back pain is generally treated with non-pharmacological therapy first, as it typically resolves without the use of medication. Superficial heat and massage, acupuncture, and spinal manipulation therapy may be recommended.

- Heat therapy is useful for back spasms or other conditions. A review concluded that heat therapy can reduce symptoms of acute and sub-acute low-back pain.

- Regular activity and gentle stretching exercises is encouraged in uncomplicated back pain, and is associated with better long-term outcomes. Physical therapy to strengthen the muscles in the abdomen and around the spine may also be recommended. These exercises are associated with better patient satisfaction, although it has not been shown to provide functional improvement. However, one study found that exercise is effective for chronic back pain, but not for acute pain. If used, they should be performed under supervision of a licensed health professional.

- Massage therapy may give short-term pain relief, but not functional improvement, for those with acute lower back pain. It may also give short-term pain relief and functional improvement for those with long-term (chronic) and sub-acute lower pack pain, but this benefit does not appear to be sustained after 6 months of treatment. There does not appear to be any serious adverse effects associated with massage.

- Acupuncture may provide some relief for back pain. However, further research with stronger evidence needs to be done.

- Spinal manipulation is a widely-used method of treating back pain, although there is no evidence of long-term benefits.

- "Back school" is an intervention that consists of both education and physical exercises. A 2016 Cochrane review found the evidence concerning back school to be very low quality and was not able to make generalizations as to whether back school is effective or not.

All destructive procedures will cause facial numbness, post relief, as well as pain relief.

- Percutaneous techniques which all involve a needle or catheter entering the face up to the origin where the nerve splits into three divisions and then damaging this area, purposely, to produce numbness but also stop pain signals. These techniques are proven effective especially in those where other interventions have failed or in those who are medically unfit for surgery such as the elderly.

- Balloon compression - inflation of a balloon at this point causing damage and stopping pain signals.

- Glycerol injection- deposition of a corrosive liquid called glycerol at this point causes damage to the nerve to hinder pain signals.

- Radiofrequency thermocoagulation rhizotomy - application of a heated needle to damage the nerve at this point.

- Stereotactic radiosurgery is a form of radiation therapy that focuses high-power energy on a small area of the body

Massage therapy using trigger-point release techniques may be effective in short-term pain relief. Physical therapy involving gentle stretching and exercise is useful for recovering full range of motion and motor coordination. Once the trigger points are gone, muscle strengthening exercise can begin, supporting long-term health of the local muscle system.

Myofascial release, which involves gentle fascia manipulation and massage, may improve or remediate the condition.

A systematic review concluded that dry needling for the treatment of myofascial pain syndrome in the lower back appeared to be a useful adjunct to standard therapies, but that clear recommendations could not be made because the published studies were small and of low quality.

Posture evaluation and ergonomics may provide significant relief in the early stages of treatment. Movement therapies such as Alexander Technique and Feldenkrais Method may also be helpful.

Gentle, sustained stretching exercises within a comfortable range of motion have been shown to decrease pain thresholds. Regular, non-intense activity is also encouraged.

Expensive and invasive, the above treatments are not guaranteed to work, and are not meeting the needs of patients. There is a need for a new, less expensive, less invasive form of treatment, two of which are postulated below.

- Spinal cord stimulation has been studied in the last couple of years. In a long case study, 8 patients were given spinal cord stimulation via insertion of a percutaneous lead at the appropriate level of the cervical or thoracic spine. Between 36 and 149 months after the stimulations, the patients were interviewed. 6 of the 8 had received initial pain relief, and three experienced long-term pain relief. Spinal cord stimulation is cheaper than brain stimulation and less invasive, and is thus a more promising option for pain treatment.

- In 2007, Dr. V. S. Ramachandran and his lab proposed that caloric stimulation might be effective in treating Dejerine–Roussy syndrome. They hypothesized that if cold water was streamed into the ear down the auditory canal, the symptoms associated with Dejerine–Roussy syndrome would be alleviated. Ramachandran stated that he had carried out provisional experiments on two patients and believed that their reactions supported his theory.

Hyperalgesia is similar to other sorts of pain associated with nerve irritation or damage such as allodynia and neuropathic pain, and consequently may respond to standard treatment for these conditions, using various drugs such as SSRI or tricyclic antidepressants, Nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, gabapentin or pregabalin, NMDA antagonists, or atypical opioids such as tramadol. Where hyperalgesia has been produced by chronic high doses of opioids, reducing the dose may result in improved pain management. However, as with other forms of nerve dysfunction associated pain, treatment of hyperalgesia can be clinically challenging, and finding a suitable drug or drug combination that is effective for a particular patient may require trial and error. The use of a transcutaneous electrical nerve stimulation device has been shown to alleviate hyperalgesia.

If drug treatment is found to be ineffective or causes disabling side effects, one of several neurosurgical procedures may be considered. The available procedures are believed to be less effective with type II (atypical) trigeminal neuralgia than with type I (typical or "classic") TN. Among present procedures, the most effective and long lasting has been found to be microvascular decompression (MVD), which seeks to relieve direct compression of the trigeminal nerve by separating and padding blood vessels in the vicinity of the emergence of this nerve from the brain stem, below the cranium.

Choice of a surgical procedure is made by the doctor and patient in consultation, based on the patient's pain presentation and health and the doctor's medical experience. Some neurosurgeons resist the application of MVD or other surgeries to atypical trigeminal neuralgia, in light of a widespread perception that ATN pain is less responsive to these procedures. However, recent papers suggest that in cases where pain initially presents as type I TN, surgery may be effective even after the pain has evolved into type II.

For secondary erythromelalgia, treatment of the underlying primary disorder is the most primary method of treatment. Although aspirin has been thought to reduce symptoms of erythromelalgia, it is rare to find evidence that this is effective. Mechanical cooling of the limbs by elevating them can help or managing the ambient environment frequently is often necessary constantly as flares occur due to sympathetic autonomic dysfunction of the capillaries. The pain that accompanies it is severe and treated separately (the pain is similar to CRPS, phantom limb or thalamic pain syndrome). Patients are strongly advised "not" to place the affected limbs in cold water to relieve symptoms when flaring occurs. It may seem a good idea, but it precipitates problems further down the line causing damage to the skin and ulceration often intractable due to the damaged skin. A possible reduction in skin damage may be accomplished by enclosing the flaring limb in a commonly available, thin, heat transparent, water impermeable, plastic food storage bag. The advice of a physician is advised depending on specific circumstances.

Primary erythromelalgia management is symptomatic, i.e. treating painful symptoms only. Specific management tactics include avoidance of attack triggers such as: heat, change in temperature, exercise or over exertion, alcohol and spicy foods. This list is by no means comprehensive as there are many triggers to set off a 'flaring' episode that are inexplicable. Whilst a cool environment is helpful in keeping the symptoms in control, the use of cold water baths is strongly discouraged. In pursuit of added relief sufferers can inadvertently cause tissue damage or death, i.e. necrosis. See comments at the end of the preceding paragraph regarding possible effectiveness of plastic food storage bags to avoid/reduce negative effects of submersion in cold water baths.

One clinical study has demonstrated the efficacy of IV lidocaine or oral mexilitine, though it should be noted that differences between the primary and secondary forms were not studied. Another trial has shown promise for misoprostol, while other have shown that gabapentin, venlafaxine and oral magnesium may also be effective, but no further testing was carried out as newer research superseded this combination.

Strong anecdotal evidence from EM patients shows that a combination of drugs such as duloxetine and pregabalin is an effective way of reducing the stabbing pains and burning sensation symptoms of erythromelalgia in conjunction with the appropriate analgesia. In some cases, antihistamines may give some relief. Most people with erythromelalgia never go into remission and the symptoms are ever present at some level, whilst others get worse, or the EM is eventually a symptom of another disease such as systemic scleroderma.

Some suffering with EM are prescribed ketamine topical creams as a way of managing pain on a long term basis. Feedback from some EM patients has led to reduction in usage as they believe it is only effective for short periods.

Living with erythromelalgia can result in a deterioration in quality of life resulting in the inability to function in a work place, lack of mobility, depression, and is socially alienating; much greater education of medical practitioners is needed. As with many rare diseases, many people with EM end up taking years to get a diagnosis and to receive appropriate treatment.

Research into the genetic mutations continues but there is a paucity of clinical studies focusing on living with erythromelalgia. There is much urgency within pharmaceutical companies to provide a solution to those who suffer with pain such as that with erythromelalgia.