Pain management a comprehensive review



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Types of headaches:

  • Primary headaches. This type of headache occurs independent of any other medical condition [26]. Researchers currently do not know exactly what mechanism sets a primary headache into motion. However, events that affect the blood vessels and nerves inside and outside the head cascade to cause pain signals that are then sent to the brain. The brain’s neurotransmitters as well as changes in the activity of nerve cells – an occurrence called cortical spreading depression – create the head pain. Primary headaches are divided into four main groupings: migraines, tension headaches, trigeminal autonomic cephalgias, and miscellaneous. Primary headache types include:

  • Migraine. Approximately 12% of people in the United States experience migraine, which is a form of vascular headache [27]. Vascular headache is characterized by pulsating, throbbing pain that is the result of the activation of nerve fibers and reside in the brain blood vessels. The blood vessels temporarily narrow, which serves to decrease the flow of blood – and therefore oxygen – to the brain. This narrowing makes other blood vessels open wider in an attempt to increase the blood flow to the brain.

Migraines often strike one side of the head. Symptoms include a throbbing, pulsing pain, sensitivity to light or sound as well as odors, and nausea or vomiting. If left untreated, migraine generally lasts between 4 and 72 hours. Even the most routine movements – such as sneezing of coughing – can worsen the pain of a migraine. The most common occurrence of migraine is in the morning hours, particularly upon waking. However, migraine can occur at any time in the day. Some individuals experience migraines at predictable times – for example, before menstruation or on the weekend after a stressful work week. Most people who experience migraine are symptom-free following a migraine.

There are two main types of migraine [27]. These are:

Migraine with aura. This is commonly considered the classic migraine. This type of migraine often includes neurologic symptoms that present from 10 to 60 minutes before onset of headache. These neurologic symptoms generally do not last more than one hour. Visual disturbances are a hallmark of the migraine with aura. Individuals may experience partial or complete vision loss while having this kind of migraine. This can occur even without the presence of a headache. Individuals also frequently have trouble speaking, experience numbing or muscle weakness, and tingling in the face or hands.

Migraine without aura. This type of migraine is commonly considered a common migraine, as it occurs more frequently than does classic migraine. Individuals frequently have sudden headache pain occurring on one side of the head that comes on with no warning. Additional symptoms include nausea, blurry vision, mood changes and confusion, and increased sensitivity to light, noise or sound.

Migraines consist of four phases. Each phase or some combination of the four may be present. These phases are:

Prodromal phase, which can occur up to 24 hours prior to migraine development. Premonitory symptoms include unexplained food cravings and mood changes, fluid retention, uncontrollable yawning, and increased urination.

Aura phase. In this phase some people see bright or flashing lights or an “aura” of light. This occurs immediately prior to onset of a migraine or during a migraine.

Headache phase. This is the phase in which the migraine starts. The migraine may build in intensity in the headache phase. Some people experience migraine with no headache.

Postdromal phase. This is the phase following the migraine attack. Individuals are frequently very tired or confused post migraine. This phase can last up to one day.

There are a number of factors that increase the risk of migraine. These factors vary from individual to individual; however, these factors include sudden changes to environment or weather, too much or not enough sleep, exposure to strong fumes or odors, strong emotions, such as stress reactions, sudden noises, low blood sugar, and bright or flashing lights. In addition, medication that is overused or missed may cause sudden migraine headache. Also, certain foods or food ingredients can trigger migraine in up to 50% of those who suffer from migraine [25]. These foods include aspartame, wine, chocolate, certain cheeses, MSG, yeast, and caffeine (or withdrawal from caffeine). Individuals can help determine which foods trigger their own migraines by keeping a detailed food journal that includes indicating the onset of migraine.



  • Tension headache. This type of headache, also commonly known as a muscle contraction headache, is the most common of the headache types. Stress, as well as mental and emotional conflicts trigger pain that originates from muscle contractions that take place in the scalp, neck, jaw, or face. This type of headache may in addition be caused by the clenching of the jaw, depression or anxiety, intense and stressful work, or lack of sleep. Sleep apnea is also a known cause of tension headaches, particularly upon waking.

Tension headache pain is frequently felt on both sides of the head and the pain often resembles the feel of a vise around the head. Tension headaches often disappear once the period of stress that caused the headache has ended. Further, depression can bring on a tension headache as can certain postures that strain the muscles of the head and neck.

There are two types of tension headaches:

Episodic headaches, which present between 10 to 15 days a month, with each episode lasting from 30 minutes to several days in length.

Chronic headaches, which generally occur more than 15 days a month over 3 months. The pain from chronic tension headache can be constant over this time and cause soreness in the scalp.



  • Trigeminal Autonomic Cephalgia. This type of headache presents as severe pain that resides in or around the eye socket, generally on one side of the face and involuntary reaction of the same side of the face, for example, red or teary eyes, droopy eyelids, or runny nose. This type of headache is considered a pain disorder that comes in both episodic and chronic forms [28]. Episodic cephalgia may occur on a daily basis for weeks or even months per year with remissions that are pain free. Chronic cephalgia may occur on a daily basis for a year or even longer, with brief or no remission period.

  • Cluster Headache. A cluster headache is considered the most severe form of primary headache. This type of headache consists of sudden and extreme headaches that occur in “clusters”, generally around the same time of day or night for weeks at a time. Cluster headaches affect one side of the head and present either around or behind one eye. This type of headache may start with a migraine-type aura and nausea. The nose and the eye on the side of the face that is affected may become red, teary, or swollen. Cluster headache frequently wakes people from sleep. Cluster headache generally is of shorter duration and frequency than is migraine headache.

This type of headache most frequently begins between ages 20 and 50, but they can present at any age. Cluster headache is more frequent in men than in women. Alcohol and smoking in particular may prompt the onset of cluster headache.

  • Paroxysmal Hemicrania. This type of primary headache is rare and generally begins in adulthood. Pain and other symptoms are similar to those that present in cluster headache, but the pain and symptoms are usually shorter in duration. Pain from paroxysmal hemicrania can occur between 5 and 40 times per day, with each headache attack between 2 and 45 minutes in duration. Pain is felt as a severe throbbing or piercing pain on one side of the face, with pain located in, around, or behind the eye and sometimes extending to the back of the neck. Additional symptoms may include watery or red eyes, swollen or drooping eyelid, or nasal congestion. Some individuals also experience pain and soreness between headache attacks and may be sensitive to light.

There are two forms of paroxysmal hemicrania [29]:

Chronic paroxysmal hemicrania. Patients experience headache attacks on a daily basis, lasting a year or longer.

Episodic paroxysmal hemicrania. Patients experience headache attacks intermittently and may go months or years before experiencing a recurrence of headache pain.

Paroxysmal hemicrania occurs more frequently in women than it does in men.

SUNCT (Short lasting, Unilateral Neuralgiform headache with Conjunctival injection and Tearing). This type of primary headache is very rare and presents with small bursts of moderate or severe piercing or throbbing pain felt in the forehead, temple, or eye. Location is usually confined to one side of the head. Other symptoms include bloodshot or reddened eyes, watering of the eyes, nasal congestion, sweating on the face, puffiness in the eyes, and increased blood pressure. Pain may peak within a few seconds of headache onset and generally follows a pattern of increasing and decreasing intensity. Headache attacks usually occur during the day and can last between 5 seconds and 4 minutes [30]. Those who experience these attacks generally experience five or six attacks per hour and do not usually have pain between attacks.

SUNCT is more common in men than it is in women. Onset is usually after 50 years of age. SUNCT also has chronic and episodic forms.

Primary headaches may also be:

Chronic episodes that occur daily for at least 15 days per month over a 3 month period, characterized by constant yet moderate pain throughout the day that is confined to the top or sides of the head.

Stabbing, in which individuals feel intense and piercing pain that comes on without warning and lasts between 1 and 10 seconds. Stabbing headache is usually a spontaneous attack, but moving suddenly or looking into bright light can prompt stabbing headache.

Exertional, in which physical exertion such as coughing or sneezing or exercise prompts headache, characterized by pain that lasts between a few minutes and 2 days, and may include nausea or vomiting.

Hypnic, which is a type of headache that wakes people primarily during the night. This type of headache typically presents after 50 years of age, and can occur 15 or more times each month and last between 15 minutes and 3 hours after the individual has woken up. Pain is dispersed to both sides of the head. There is no known trigger of hypnic headache; however, researchers believe that these attacks may be a disorder that occurs during REM sleep.

Ice cream headache”. This type of headache occurs when the individual has inhaled or eaten something cold very fast. These attacks last for approximately 5 minutes and stop when the body adapts to the abrupt temperature change. “Ice cream headaches” are more common in those individuals who experience migraine.



  • Secondary headache. Secondary headaches occur as a symptom of some other medical condition [31]. Secondary headaches may occur as a result of conditions such as infection, high blood pressure, fever, medication overuse, stress or conflict, tumors, stroke, head trauma, or mental disorders. Some of these causes are more serious than others.

Serious causes of secondary headache include:

    • Brain tumor. Tumors in the brain can press against the nerves and blood vessel walls, which in turn disrupts communication and limits the supply of blood to the brain. Headache is intermittent and can develop or worsen, come or go, and become more frequent or infrequent at irregular periods. Headache pain generally worsens when performing certain exertional activities, such as coughing, or when changing physical position very suddenly. Brain tumors are rare among those who experience headache.

    • Stroke. Headache can cause a stroke or be the result of a stroke, where blood vessel activity is altered.

There are two types of stroke:

Hemorrhagic stroke. This form of stroke occurs when an artery bursts in the brain. Hemorrhagic stroke is generally associated with brain function that is disturbed and a sudden and extremely painful headache that worsens with such events as coughing or physical activity.



Ischemic stroke, in which an artery in the brain becomes blocked, which decreases or stops the flow of blood to the brain, leading to cell death. Headache commonly occurs in those individuals who have clotting in the brain’s veins, with pain occurring on the side of the head where the clot is blocking blood flow. Pain frequently radiates out to the eyes or on the side of the head.

    • Exposure to or withdrawal from certain substances. Headache can occur as a response to a toxic state, for example, drinking alcohol, being exposed to large doses of carbon monoxide, or from exposure to toxic chemicals found in cleaning products or pesticide. Headache response to a toxic state typically includes a pulsing and throbbing pain that increases with intensity the longer the individual is exposed to the substance. If left untreated, toxic exposure can cause permanent neurological damage as well as damage to organ systems within the body. Additionally, experiencing withdrawal from certain medications or from caffeine after heavy use can prompt headache.

    • Head injury. Headache frequently occurs post-trauma and can be a symptom of concussion or other types of head injury. Pain is generally felt close to the site of injury, with pain radiating out through the head. The cause of headache that results from a trauma is frequently unknown; however, causes may include hematoma.

    • An increase in intracranial pressure. Pressure changes in the brain may be caused by infections, hydrocephalus, or brain tumors that are increasing in size. These pressure changes frequently lead to headache with pain that is felt at the site of blood vessel compression or displacement, and radiates throughout the head.

    • Inflammation occurring as a result of meningitis or encephalitis. Inflammation from these types of infections may harm and destroy nerve cells. The result is headache pain that can range from dull to very severe. Other results include brain damage or stroke. These conditions require immediate medical attention. Additionally, headache can occur as a result of other infections, such as the flu or a bacterial infection. Inflammation of the sinuses in conditions such as the flu results in facial pain that becomes worse if the individual strains or makes certain movements of the head.

    • Seizure. Pain that is comparable to migraine can occur during or after seizure. The pain presents as moderate to severe, and lasts for a few hours. Pain can become worse if the individual moves their head suddenly or during physical exertion such as coughing. Symptoms also include nausea or vomiting, fatigue, and vision problems that can include sensitivity to light.

    • Leaking of spinal fluid. Individuals who undergo lumbar puncture may experience headache that results from leakage of the cerebrospinal fluid post-procedure. Headache pain only occurs when the individual is standing; therefore, it is necessary for the individual to lie down and let the headache run its course. Headache resulting from a spinal fluid leak can last from a few hours to a few days.

    • Abnormalities to the structure of the head, neck, or spine. Abnormalities of structure to the head, neck, or spine can cause headache. This frequently results from such abnormalities as a restriction of blood flow through the neck or irritation of nerves along the spinal pathway. This type of headache can also be the result of holding the head in a stressful or awkward position. Additionally, this headache can be the result of conditions such as chiari malformation or syringomyelia.

    • Trigeminal neuralgia. Headache pain is caused in this condition by pressure placed on the trigeminal nerve, which sends sensations to the brain from certain portions of the face and mouth [32]. This type of headache presents as shocking or stabbing pain that occurs suddenly and is typically only present on one side of the jaw. Muscle spasms of the face may also occur. Headache may occur spontaneously or be triggered when the cheek is touched through routine activities, such as washing the face. Additionally, pain can be triggered through activity of the mouth, such as that activity that occurs with eating, talking, or brushing teeth.

Individuals should see a doctor for headache under certain circumstances, as some types of headache can indicate the existence of serious medical conditions. Individuals should see a doctor immediately if they experience any of the following symptoms:

      • Headache with sudden and severe onset that is accompanied by stiffness in the neck.

      • Headache that includes nausea or vomiting or fever that can not be attributed to another illness.

      • First occurrence of headache that is accompanied by weakness or confusion, or lack of consciousness.

      • Headache that continually worsens as days or weeks passed, or headache that changes in pattern.

      • Headache that recurs in children.

      • Headache that occurs following injury to the head.

      • Headache that is accompanied by weakness or loss of sensation in the body. This can indicate stroke.

      • Headache that includes convulsions.

      • Headache that includes shortness of breath.

      • Headache that occurs two or more times per week.

      • Sudden and persistent headache in an individual who was previously without headaches, particularly if the individual is more than 50 years of age.

      • New headache in those individuals who have a history of HIV/AIDS or cancer.

C. Etiology- Burn pain and postherpetic neuralgia

Burn injuries can be extremely painful and disfiguring since they affect the largest organ in the body, the skin. These injuries, when major, can be disabling [33]. Approximately 45% of burn injury affects children and requires hospital admission [34]. Early pain management can significantly influence how the individual experiences pain resulting from burn injury later on.

Pain in burn injury is affected by how large and deep the injury goes. Additionally, pain may be exacerbated by conditions resulting from the injury, such as infections. Burn pain is frequently difficult to manage, and as a result may be undertreated.

When an individual feels the immediate pain following a burn injury, it is the result of stimulation of skin nociceptors whose job it is to respond to heat as well as both exogenous and endogenous stimuli. If the nerve endings are entirely destroyed by the injury they will not transmit pain signals, but undamaged nerve endings or others exposed to the injury will transmit pain over the course of treatment for the injury.

Additionally, complications arise through the emergence of primary hyperalgesia and secondary hyperalgesia [35]:


  • Primary hyperalgesia. A burn initiates a very powerful inflammatory response, and inflammatory mediators are released, which sensitizes the nociceptors at the injury site. This makes the area of injury as well as the skin immediately adjacent to the injury become sensitive to certain mechanical stimuli, including touching or rubbing as well as to certain chemical stimuli, including the application of antiseptics or topical ointments.

  • Secondary hyperalgesia. Continuous peripheral stimulation of nociceptors causes greater sensitivity to areas surrounding the area of injury. This sensitivity is exacerbated by certain mechanical stimulation, such as that which occurs from changing wound dressing frequently.

Burns differ in size and degree, which results in differing pain dependent on these factors. Conventionally, burns are classified by the total area of the body surface that was burned as well as depth of the burn. Simple observation may indicate that the larger or deeper the burn is, the more pain the person will feel. Realistically however, even deep burns consist of a combination of depth where the nerve endings were damaged as well as more shallow areas where some of the nerve endings are undamaged. Therefore, all burns elicit a pain response, and it is important that each instance be treated well and thoroughly. Additionally, psychological factors – such as anxiety over the new appearance of the area that was burned – also play an important role in how much pain the individual experiences.

There is also more than one type of pain seen in the burn recovery process:



  • Initial acute pain. Energy from the source of the burn leads to cell damage and the release of mediators. Individuals also experience reflex activity as a result of a burn, in which they attempt to remove the area that has been affected from the source to avoid further injury. However, this action is not always a possibility, and the individual ends up with a more severe injury. Additionally, sometimes the patient experiences stress-induced analgesia, in which the release of endorphins in the spinal cord results in there being either little or no pain immediately following the injury.

  • Pain following hospitalization. A patient may experience various pain classifications following a burn injury. One is procedural pain that is of short to medium duration. This pain can feel highly intense during or immediately following the cleaning of the affected area or when procedures such as skin grafting take place. A patient may also have resting pain, which presents as a dull pain that is of long duration. This type of pain frequently exists when the patient is between procedures. Finally, the patient may experience breakthrough pain. This type of pain is usually of short duration and is linked with resting pain.

Further, there is risk that the changes in damaged nerve fibers and surrounding tissues may lead to the development of chronic pain. In chronic pain syndromes, the sensation of pain continues for much longer than its expected duration. Chronic pain following burn injury can lead to other problems, such as difficulty sleeping, depression, and impairment of rehabilitation. The individual may experience hyperalgesia or allodynia. These issues may start very early in the post-injury course of recovery and can persist for a number of years following the initial injury. Chronic burn pain is extremely difficult to treat utilizing most analgesics unless there is inflammation or damage to tissues that is ongoing. Therefore, treatment of chronic burn pain frequently involves antidepressants, anticonvulsants, nerve blocks, or cognitive behavioural therapy.

Postherpetic neuralgia occurs as a complication of shingles, which is caused by the same virus that causes chicken pox. Once an individual has had chicken pox, the virus that caused the disease remains inside the body for the rest of the individual’s life [36]. However, as the individual ages, the virus may reactivate. A number of things can cause this reactivation, including physical stress, such as that which occurs when the body is battling an infection or if the individual is taking medication that suppresses the immune system. The resulting infection is shingles. The shingles rash occurs in the areas of skin that contain the nerve where the virus was reactivated. Shingles generally clears up within several weeks. However, if there is pain lasting long after shingles has disappeared, it is termed postherpetic neuralgia.

Postherpetic neuralgia affects the skin and the nerve fibers, and occurs if nerve fibers are damaged during a shingles outbreak. The damaged fibers are unable to send messages from the skin to the brain in a normal way, and instead sends confusing or exaggerated messages, which causes chronic – and frequently excruciating – pain that can last for months or years.

Pain presents as a burning sensation and can be so severe that it interferes with functions such as sleep and appetite. Those who are 60 years of age and older have the greatest risk of developing postherpetic neuralgia. Those who have shingles on the face are also at greater risk of developing postherpetic neuralgia as opposed to those who experience shingles on other parts of the body. There is currently no cure for the condition, but treatment options exist that can ease pain symptoms. For many, the condition improves as time passes.


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