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:

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

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.

A trial of the anticonvulsant drug carbamazepine is common for patients diagnosed with GN. For patients who do not tolerate or respond to carbamazepine, alternative drugs include oxcarbazepine, gabapentin, phenytoin, lamotrigine, and baclofen. In addition, tricyclics (e.g., amitriptyline) and pregabalin are useful in other types of neuropathic pain.

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.

Tension-type headaches can usually be managed with NSAIDs (ibuprofen, naproxen), acetaminophen or aspirin. Triptans are not helpful in tension-type headaches unless the person also has migraines. For chronic tension type headaches, amitriptyline is the only medication proven to help. Amitriptyline is a medication which treats depression and also independently treats pain. It works by blocking the reuptake of serotonin and norepinephrine, and also reduces muscle tenderness by a separate mechanism. Studies evaluating acupuncture for tension-type headaches have been mixed. Overall, they show that acupuncture is probably not helpful for tension-type headaches.

The other primarily recommended treatment of acute attacks is subcutaneous or intranasal sumatriptan. Sumatriptan and zolmitriptan have both been shown to improve symptoms during an attack with sumatriptan being superior. Because of the vasoconstrictive side-effect of triptans, they may be contraindicated in people with ischemic heart disease.

In 1995, the Food and Drug Administration (FDA) approved the Varicella vaccine to prevent chickenpox. Its effect on postherpetic neuralgia is still unknown. The vaccine—made from a weakened form of the varicella-zoster virus—may keep chickenpox from occurring in nonimmune children and adults, or at least lessen the risk of the chickenpox virus lying dormant in the body and reactivating later as shingles. If shingles could be prevented, postherpetic neuralgia could be completely avoided.

In May 2006 the Advisory Committee on Immunization Practices approved a new vaccine by Merck (Zostavax) against shingles. This vaccine is a more potent version of the chickenpox vaccine, and evidence shows that it reduces the incidence of postherpetic neuralgia. The CDC recommends use of this vaccine in all persons over 60 years old.

A variety of surgeries have been performed including microvascular decompression (MVD) of the fifth, ninth, and tenth nerves; as well as partial cutting of the nervus intermedius, geniculate ganglion, chorda tympani and/or the ninth and tenth cranial nerves.

Lithium, methysergide, and topiramate are recommended alternative treatments, although there is little evidence supporting the use of topiramate or methysergide. This is also true for tianeptine, melatonin and ergotamine. Valproate, sumatriptan and oxygen are not recommended as preventative measures. Botulinum toxin injections have shown limited success. Evidence for baclofen, botulinum toxin, and capsaicin is unclear.

Migraine can be somewhat improved by lifestyle changes, but most people require medicines to control their symptoms. Medications are either to prevent getting migraines, or to reduce symptoms once a migraine starts.

Preventive medications are generally recommended when people have more than four attacks of migraine per month, headaches last longer than 12 hours or the headaches are very disabling. Possible therapies include beta blockers, antidepressants, anticonvulsants and NSAIDs. The type of preventive medicine is usually chosen based on the other symptoms the person has. For example, if the person also has depression, an antidepressant is a good choice.

Abortive therapies for migraines may be oral, if the migraine is mild to moderate, or may require stronger medicine given intravenously or intramuscularly. Mild to moderate headaches should first be treated with acetaminophen (paracetamol) or NSAIDs, like ibuprofen. If accompanied by nausea or vomiting, an antiemitic such as metoclopramide (Reglan) can be given orally or rectally. Moderate to severe attacks should be treated first with an oral triptan, a medication which mimics serotonin (an agonist) and causes mild vasoconstriction. If accompanied by nausea and vomiting, parenteral (through a needle in the skin) triptans and antiemetics can be given.

Several complementary and alternative strategies can help with migraines. The American Academy of Neurology guidelines for migraine treatment in 2000 stated relaxation training, electromyographic feedback and cognitive behavioral therapy may be considered for migraine treatment, along with medications.

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.

An April 2013 Cochrane Collaboration meta-analysis of 6 randomized controlled trials (RCTs) investigating oral antiviral medications given within 72 hours after the onset of herpes zoster rash in immunocompetent people for preventing postherpetic neuralgia (PHN) found no significant difference between placebo and acyclovir. Combining four RCTs, 44.1% of the acyclovir treatment group developed herpetic neuralgia whereas 53.3% of the placebo group developed herpetic neuralgia. Heterogeneity between the four RCTs was moderate: Chi =3.36, df = 2 (P=0.19); I = 40%.

Additionally, there was no significant difference in preventing the incidence of PHN found in the one RCT included in the meta-analysis that compared placebo to PO famciclovir treatment within 72 hours of HZ rash onset. Studies using valaciclovir treatment were not included in the meta-analysis.

PHN was defined as pain at the site of the dermatomic rash at 120 days after the onset of rash, and incidence was evaluated at 1, 4, and 6 months after rash onset.

There was a slight reduction in the incidence of pain at 4 weeks after the onset of rash in the aciclovir group (153 study participants with pain out of 347 study participants in the aciclovir group) versus the placebo group (184 study participants with pain out of 345 study participants in the placebo group). Patients who are prescribed PO antiviral agents after the onset of rash should be informed that their chances of developing PHN are no different than those not taking PO antiviral agents.

A randomized controlled trial found that amitriptyline 25 mg per night for 90 days starting within two days of onset of rash can reduce the incidence of postherpetic neuralgia from 35% to 16% (number needed to treat is 6).

There are numerous pharmaceutical treatments for neuropathic pain associated with pudendal neuralgia. Drugs used include anti-epileptics (like gabapentin), antidepressants (like amitriptyline), and palmitoylethanolamide.

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.

Optional treatments include behavioral modifications, physical therapy, analgesics and other medications, pudendal nerve block, and surgical nerve decompression. A newer form of treatment is pulsed radiofrequency.

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.

Hemicrania continua generally responds only to indomethacin 25–300 mg daily, which must be continued long term. Unfortunately, gastrointestinal side effects are a common problem with indomethacin, which may require additional acid-suppression therapy to control.

In patients who are unable to tolerate indomethacin, the use of celecoxib 400–800 mg per day (Celebrex) and rofecoxib 50 mg per day (Vioxx - no longer available) have both been shown to be effective and are likely to be associated with fewer GI side effects. There have also been reports of two patients who were successfully managed with topiramate 100–200 mg per day (Topamax) although side effects with this treatment can also prove problematic.

Greater Occipital Nerve [GON] block comprising 40 mg Depomedrone and 10mls of 1% Lignocaine injected into the affected nerve is effective, up to a period of approximately three months. Changing the 'cocktail' to include [for example] 10mls of .5% Marcaine and changing to 2% Lignocaine, whilst in theory should increase the longevity, renders the injection completely ineffective. See 4.2 Posology and method of administration [flocculation]

Occipital nerve stimulation may be highly effective when other treatments fail to relieve the intractable pain.

Some have suggested that surgery is not an appropriate for treatment for AFP, however the frequent failure medical treatment to relieve pain has occasionally lead surgeons to attempt surgical treatments. Surgery may give a temporary remission from pain, but rarely is there a long term cure achieved via these measures. Sometimes the pain may be increased or simply migrate to an adjacent area following a surgical procedure. Descriptions of procedures such as removal of a portion of the affected branch of the trigeminal nerve, or direct injections of a caustic substance (e.g. phenol, glycerol, alcohol) into the nerve have been reported. Proponents of the so-called "Neuralgia inducing cavitational necrosis" suggest surgical exploration of the bone marrow surrounding the intra-bony course of the affected nerve to discover diseased marrow.

Psychosocial interventions for AFP include cognitive behavioral therapy and biofeedback. A systematic review reported that there was weak evidence to support the use of these treatments to improve long-term outcomes in chronic orofacial pain, however these results were based primarily upon temporomandibular joint dysfunction and burning mouth syndrome rather than ATP and AO.

Psychosocial interventions assume 2 models of chronic facial pain, namely "inactivity" and "over activity". The former is where people with pain become conditioned to avoid physical activity as a result of exacerbating their pain. These negative thoughts and behaviors in fact prolong and intensify their symptoms. Some psychosocial interventions work on this fear-avoidance behaviour to improve functioning and thereby alleviate symptoms. The over activity model involves factors such as anxiety, depression or anger acting to increase pain by triggering autonomic, visceral and skeletal activity.

Arachnoiditis is difficult to treat and treatment is generally limited to alleviation of pain and other symptoms. While arachnoiditis may not yet be curable and can be significantly life-altering, management of the condition, including with medication, physical therapy, and if appropriate, psychotherapy, can help patients cope with the difficulties it presents. Surgical intervention generally has a poor outcome and may only provide temporary relief, but some cases of surgical success have been reported. Epidural steroid injections to treat sciatic pain have been linked as a "cause" of the disease by the U.S. Food and Drug Administration as well as in other research, and are therefore discouraged as a treatment for Arachnoiditis as they will most likely worsen the condition. Some patients benefit from motorized assistance devices such as the Segway or standing wheelchairs, although these types of devices may be beyond the reach of those with limited means. Standing endurance and vibration tolerance are considered before considering such devices in any case.

Traditional remedies have ranged from warm baths (if the pain lasts long enough to draw a bath), warm to hot enemas, relaxation techniques, and various medications.

Yoga pose "downward facing dog" -Adho Mukha Svanasana, or modification from it seems to help to relax the muscles and ease the pain. The idea of the yoga pose is that the position will force the muscles to relax and therefore tension will relieve over time. Also relaxing one's jaw muscles will help to relax the muscles in rectal area, method used by women giving birth.

In patients who suffer frequent, severe, prolonged attacks, inhaled salbutamol has been shown in some studies to reduce their duration.

The use of botulinum toxin has been proposed as analgesic, and low dose diazepam at bedtime has been suggested as preventative.

The most common approach for mild cases is simply reassurance and topical treatment with calcium-channel blocker (diltiazem, nifedipine) ointment, salbutamol inhalation and sublingual nitroglycerine.For persistent cases, local anesthetic blocks, clonidine or Botox injections can be considered. Supportive treatments directed at aggravating factors include high-fiber diet, withdrawal of drugs which have gut effects (e.g., drugs that provoke or worsen constipation including narcotics and oral calcium channel blockers; drugs that provoke or worsen diarrhea including quinidine, theophylline, and antibiotics), warm baths, rectal massage, perineal strengthening exercises, anti-cholinergic agents, non-narcotic analgesics, sedatives or muscle relaxants such as diazepam.

Management of ear pain depends on the underlying cause.Most cases of otitis media are self-limiting, resolving spontaneously without treatment within 3–5 days. Age-appropriate analgesics or a warm washcloth placed over the affected ear can help relieve pain until the infection has passed.In some cases ear pain has been treated successfully with manual therapy.

Medication is the main method of managing pain in TMD, mostly because there is little if any evidence of the effectiveness of surgical or dental interventions. Many drugs have been used to treat TMD pain, such as analgesics (pain killers), benzodiazepines (e.g. clonazepam, prazepam, diazepam), anticonvulsants (e.g. gabapentin), muscle relaxants (e.g. cyclobenzaprine), and others. Analgesics that have been studied in TMD include non-steroidal anti-inflammatory drugs (e.g. piroxicam, diclofenac, naproxen) and cyclo-oxygenase-2 inhibitors (e.g. celecoxib). Topical methyl salicylate and topical capsaicin have also been used. Other drugs that have been described for use in TMD include glucosamine hydrochloride/chondroitin sulphate and propranolol. Despite many randomized control trials being conducted on these commonly used medications for TMD a systematic review carried out in 2010 concluded that there was insufficient evidence to support or not to support the use of these drugs in TMD. Low-doses of anti-muscarinic tricyclic antidepressants such as amitriptyline, or nortriptyline have also been described. In a subset of people with TMD who are not helped by either noninvasive and invasive treatments, long term use of opiate analgesics has been suggested, although these drugs carry a risk of drug dependence and other side effects. Examples include morphine, fentanyl, oxycodone, tramadol, hydrocodone, and methadone.

Botulinum toxin solution ("Botox") is sometimes used to treat TMD. Injection of botox into the lateral pterygoid muscle has been investigated in multiple randomized control trials, and there is evidence that it is of benefit in TMD. It is theorized that spasm of lateral pterygoid causes anterior disc displacement. Botulinum toxin causes temporary muscular paralysis by inhibiting acetylcholine release at the neuromuscular junction. The effects usually last for a period of months before they wear off. Complications include the creation of a "fixed" expression due to diffusion of the solution and subsequent involvement of the muscles of facial expression, which lasts until the effects of the botox wear off. Injections of local anesthetic, sometimes combined with steroids, into the muscles (e.g. the temoralis muscle or its tendon) are also sometimes used. Local anesthetics may provide temporary pain relief, and steroids inhibit pro-inflammatory cytokines. Steroids and other medications are sometimes injected directly into the joint (See Intra-articular injections).

High-voltage pulsed galvanic stimulation (HGVS) has been shown to be of prophylactic benefit, to reduce the incidence of attacks. The patient is usually placed in the left lateral decubitus position and a sterile probe is inserted into the anus. The negative electrode is used and the stimulator is set with a pulse frequency of 80 to 120 cycles per second. The voltage (intensity) is started at 0, progressively raised to a threshold of patient discomfort, and then is decreased to a level that the patient finds comfortable. As the patient's tolerance increases, the voltage can be gradually increased to 250 to 350 Volts. Each treatment session usually lasts between 15 and 60 minutes. Several studies have reported short-term success rates that ranged from 65 to 91%.