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.

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.

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."

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.

Numerous compounds alleviate the pain from allodynia. Some are specific for certain types of allodynia while others are general. They include:

- Dynamic mechanical allodynia - compounds targeting different ion channels; opioids

- Mexiletine

- Lidocaine (IV/topical)

- Tramadol

- Morphine (IV)

- Alfentanil (IV)

- Ketamine (IV)

- Methylprednisone (intrathecal)

- Adenosine

- Glycine antagonist

- Desipramine

- Venlafaxine

- Lyrica

- Static mechanical allodynia - sodium channel blockers, opioids

- Lidocaine (IV)

- Alfentanil (IV)

- Adenosine (IV)

- Ketamine (IV)

- Glycine antagonist

- Venlafaxine

- Gabapentin (may also be helpful in cold and dynamic allodynias)

- Cold allodynia

- Lamotrigine

- Lidocaine (IV)

The list of compounds that can be used to treat allodynia is even longer than this. For example, many non-steroidal anti-inflammatory drugs, such as naproxen, can inhibit COX-1 and/or COX-2, thus preventing the sensitization of the central nervous system. Another effect of naproxen is the reduction of the responsiveness of mechano- and thermoreceptors to stimuli.

Other compounds act on molecules important for the transmission of an action potential from one neuron to another. Examples of these include interfering with receptors for neurotransmitters or the enzymes that remove neurotransmitters not bound to receptors.

Endocannabinoids are molecules that can relieve pain by modulating nociceptive neurons. When anandamide, an endocannabinoid, is released, pain sensation is reduced. Anandamide is later transported back to the neurons releasing it using transporter enzymes on the plasma membrane, eventually disinhibiting pain perception. However, this re-uptake can be blocked by AM404, elongating the duration of pain inhibition.

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.

Medications offered can include the immunosuppressant prednisone, intravenous gamma globulin (IVIG), anticonvulsants such as gabapentin or Gabitril and antiviral medication, depending on the underlying cause..

In addition to treatment of the underlying disorder, palliative care can include the use of topical numbing creams, such as lidocaine or prilocaine. Care must be taken to apply only the necessary amount, as excess can contribute to the condition. Otherwise, these products offer extremely effective, but short-lasting, relief from the condition.

Paresthesia caused by stroke may receive some temporary benefit from high doses of Baclofen multiple times a day. HIV patients who self-medicate with cannabis report that it reduces their symptoms.

Paresthesia caused by shingles is treated with appropriate antiviral medication.

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.

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.

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.

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

When an underlying medical condition is causing the neuropathy, treatment should first be directed at this condition. For example, if weight gain is the underlying cause, then a weight loss program is the most appropriate treatment. Compression neuropathy occurring in pregnancy often resolves after delivery, so no specific treatment is usually required. Some compression neuropathies are amenable to surgery: carpal tunnel syndrome and cubital tunnel syndrome are two common examples. Whether or not it is appropriate to offer surgery in any particular case depends on the severity of the symptoms, the risks of the proposed operation, and the prognosis if untreated. After surgery, the symptoms may resolve completely, but if the compression was sufficiently severe or prolonged then the nerve may not recover fully and some symptoms may persist. Drug treatment may be useful for an underlying condition (including peripheral oedema), or for ameliorating neuropathic pain.

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.

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.

Daily oral muscle physical therapy, or the administration of antidepressants have been reported as effective therapy for occlusal dysesthesia patients. Tooth grinding, and the replacement or removal of all dental work should be avoided in patients with occlusal dysesthesia, despite the frequent requests for further surgery often made by these patients.

Antidepressants are also often prescribed for scalp dysesthesia.

Prakash et al. found that many patients suffering from burning mouth syndrome (BMS), one variant of occlusal dysesthesia, also report painful sensations in other parts of the body. Many of the patients suffering from BMS met the classification of restless leg syndrome (RLS). About half of these patients also had a family history of RLS. These results suggest that some BMS symptoms may be caused by the same pathway as RLS in some patients, indicating that dopaminergic drugs regularly used to treat RLS may be effective in treating BMS as well.

CIPA sufferers have to live an extremely cautious life, incorporating numerous controls as part of their daily routine. Every morning it will be necessary to check for bruises, scratches or other injuries that might have taken place during sleeping hours, as it is very common for CIPA patients to injure themselves unknowingly. Temperature measuring must be done constantly, as well as urination control, by setting alarms or other reminders.

If any kind of accident has been suffered, regardless of its type and severity, CIPA patients must go through a thorough check for compromising injuries.

At young ages, permanent surveillance is vital. A lack of awareness of the extreme dangers this condition represents condemns the infant to a complete lack of tools against risk situations.

There are several other procedures a CIPA patient has to undergo in order to live a safe life. Those mentioned above were extracted from a “Doctor House” episode (Insensitive).

A range of medications that act on the central nervous system has been found to be useful in managing neuropathic pain. Commonly used treatments include tricyclic antidepressants (such as nortriptyline or amitriptyline), the serotonin-norepinephrine reuptake inhibitor (SNRI) medication duloxetine, and antiepileptic therapies such as gabapentin, pregabalin, or sodium valproate. Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.

Symptomatic relief for the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. The evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option. Local anesthesia often is used to counteract the initial discomfort of the capsaicin. Some current research in animal models has shown that depleting neurotrophin-3 may oppose the demyelination present in some peripheral neuropathies by increasing myelin formation.

High-quality evidence supports the use of cannabis for neuropathic pain.

If a cause can be identified for a burning sensation in the mouth, then treatment of this underlying factor is recommended. If symptom persist despite treatment a diagnosis of BMS is confirmed. BMS has been traditionally treated by reassurance and with antidepressants, anxiolytics or anticonvulsants. A 2016 Cochrane review of treatment for burning mouth syndrome concluded that strong evidence of an effective treatment was not available. Other treatments which have been used include atypical antipsychotics, histamine receptor antagonists, and dopamine agonists.

The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus or prediabetes, blood sugar management is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy. In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin or steroids. When peripheral neuropathy results from vitamin deficiencies or other disorders, those are treated as well.

Some degree of control of the fasciculations may be achieved with the same medication used to treat essential tremor (beta-blockers and anti-seizure drugs). However, often the most effective approach to treatment is to treat any accompanying anxiety. No drugs, supplements, or other treatments have been found that completely control the symptoms. In cases where fasciculations are caused by magnesium deficiency, supplementing magnesium can be effective in reducing symptoms.

In many cases, the severity of BFS symptoms can be significantly reduced through a proactive approach to decrease the overall daily stress. Common ways to reduce stress include: exercising more, sleeping more, working less, meditation, and eliminating all forms of dietary caffeine (e.g. coffee, chocolate, cola, and certain over-the counter medications).

If pain or muscle aches are present alongside fasciculations, patients may be advised to take over-the-counter pain medications such as ibuprofen or acetaminophen during times of increased pain. Other forms of pain management may also be employed. Prior to taking any over-the-counter medications, individuals should initiate discussions with their health care provider(s) to avoid adverse effects associated with long-term usage or preexisting conditions.

Treatment is based on the underlying cause, if any. Where the likely underlying condition is known, treatment of this condition is indicated treated to reduce progression of the disease and symptoms. For cases without those conditions, there is only symptomatic treatment.

Paresthesia or "persistent anesthesia" is a transient or potentially permanent condition of extended numbness after administration of local anesthesia and the injected anesthetic has terminated.

Potential causes include trauma induced to the nerve sheath during administration of the injection, hemorrhage about the sheath, type of anesthetic used, or administration of anesthetic potentially contaminated with alcohol or sterilizing solutions.

Although dysesthesia is similar to phantom limb syndrome, they should not be confused. In phantom limb, the sensation is present in an amputated or absent limb, while dysesthesia refers to discomfort or pain in a tissue that has not been removed or amputated. The dysesthetic tissue may also not be part of a limb, but part of the body, such as the abdomen. The majority of individuals with both phantom limb and dysesthesia experience painful sensations.

Phantom pain refers to dysesthetic feelings in individuals who are paralyzed or who were born without limbs. It is caused by the improper innervation of the missing limbs by the nerves that would normally innervate the limb. Dysesthesia is caused by damage to the nerves themselves, rather than by an innervation of absent tissue.

Dysesthesia should not be confused with anesthesia or hypoesthesia, which refer to a loss of sensation, or paresthesia which refers to a distorted sensation. Dysesthesia is distinct in that it can, but not necessarily, refer to spontaneous sensations in the absence of stimuli. In the case of an evoked dysesthetic sensation, such as by the touch of clothing, the sensation is characterized not simply by an exaggeration of the feeling, but rather by a completely inappropriate sensation such as burning.

Physical therapy can be somewhat useful for patient’s recovery from surgery. The main focus of rehabilitation is centered on controlling the bladder and bowel functions and decreasing muscle weakness in the lower extremities.