Hyperalgesia can be experienced in focal, discrete areas, or as a more diffuse, body-wide form. Conditioning studies have established that it is possible to experience a learned hyperalgesia of the latter, diffuse form.

The focal form is typically associated with injury, and is divided into two subtypes:

- "Primary hyperalgesia" describes pain sensitivity that occurs directly in the damaged tissues.

- "Secondary hyperalgesia" describes pain sensitivity that occurs in surrounding undamaged tissues.

Opioid-induced hyperalgesia may develop as a result of long-term opioid use in the treatment of chronic pain. Various studies of humans and animals have demonstrated that primary or secondary hyperalgesia can develop in response to both chronic and acute exposure to opioids. This side effect can be severe enough to warrant discontinuation of opioid treatment.

Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves. Prostaglandins E and F are largely responsible for sensitizing the nociceptors. Temporary increased sensitivity to pain also occurs as part of sickness behavior, the evolved response to infection.

There are different kinds or types of allodynia:

- Mechanical allodynia (also known as tactile allodynia)

- Static mechanical allodynia – pain in response when touched

- Dynamic mechanical allodynia – pain in response to stroking lightly

- Thermal (hot or cold) allodynia – pain from normally mild skin temperatures in the affected area

- Movement allodynia – pain triggered by normal movement of joints or muscles

Allodynia (Ancient Greek "" "állos" "other" and "" "odúnē" "pain") refers to central pain sensitization (increased response of neurons) following normally non-painful, often repetitive, stimulation. Allodynia can lead to the triggering of a pain response from stimuli which do not normally provoke pain. Temperature or physical stimuli can provoke allodynia, which may feel like a burning sensation, and it often occurs after injury to a site. Allodynia is different from hyperalgesia, an extreme, exaggerated reaction to a stimulus which is normally painful.

Clinical features of CRPS have been found to be inflammation resulting from the release of certain pro-inflammatory chemical signals from the nerves, sensitized nerve receptors that send pain signals to the brain, dysfunction of the local blood vessels' ability to constrict and dilate appropriately, and maladaptive neuroplasticity.

The signs and symptoms of CRPS usually initially manifest near the site of a (typically minor) injury. The most common symptoms are pain sensations, including burning, stabbing, grinding, and throbbing. Moving or touching the limb is often intolerable. The patient may also experience muscle spasms; local swelling; extreme sensitivity to things such as wind and water, touch and vibrations; abnormally increased sweating; changes in skin temperature (usually hot but sometimes cold) and color (bright red or a reddish violet); softening and thinning of bones; joint tenderness or stiffness; changes in nail and hair growth and/or restricted or painful movement. Drop attacks (falls), almost fainting, and fainting spells are infrequently reported, as are visual problems. The symptoms of CRPS vary in severity and duration. Since CRPS is a systemic problem, potentially any organ can be affected.

The pain of CRPS is continuous although varies in severity. It is widely recognized that it can be heightened by emotional or physical stress.

Previously it was considered that CRPS had three stages; it is now believed that people affected by CRPS do not progress through these stages sequentially. These stages may not be time-constrained and could possibly be event-related, such as ground-level falls or re-injuries of previously damaged areas. Thus, rather than a progression of CRPS from bad to worse, it is now thought, instead, that such individuals are likely to have one of the three following types of disease progression:

1. "Stage" one is characterized by severe, burning pain at the site of the injury, muscle spasms, joint stiffness, restricted mobility, rapid hair and nail growth, and vasospasm. The vasospasm is that which causes the changes in the color and temperature of the skin. Some may experience hyperhydrosis (increased sweating). In mild cases this stage lasts a few weeks, in which it can subside spontaneously or respond rapidly to treatment (physical therapy, pain specialist).

2. "Stage" two is characterized by more intense pain. Swelling spreads, hair growth diminishes, nails become cracked, brittle, grooved and spotty, osteoporosis becomes severe and diffuse, joints thicken, and muscles atrophy.

3. "Stage" three is characterized by irreversible changes in the skin and bones, while the pain becomes unyielding and may involve the entire limb. There is marked muscle atrophy, severely limited mobility of the affected area, and flexor tendon contractions (contractions of the muscles and tendons that flex the joints). Occasionally the limb is displaced from its normal position, and marked bone softening and thinning is more dispersed.

Hyperpathia is a clinical symptom of certain neurological disorders wherein nociceptive stimuli evoke exaggerated levels of pain. This should not be confused with allodynia, where normally non-painful stimuli evoke pain.

Opioid-induced hyperalgesia or opioid-induced abnormal pain sensitivity, also called paradoxical hyperalgesia is a phenomenon associated with the long-term use of opioids such as morphine, hydrocodone, oxycodone, and methadone. Over time, individuals taking opioids can develop an increasing sensitivity to noxious stimuli, even evolving a painful response to previously non-noxious stimuli (allodynia). Some studies on animals have also demonstrated this effect occurring after only a single high dose of opioids.

Tolerance, another condition that can arise from prolonged exposure to opioids, can often be mistaken for opioid-induced hyperalgesia and vice-versa, as the clinical presentation can appear similar. Although tolerance and opioid-induced hyperalgesia both result in a similar need for dose escalation to receive the same level of effect to treat pain, they are nevertheless caused by two distinct mechanisms. The similar net effect makes the two phenomena difficult to distinguish in a clinical setting. Under chronic opioid treatment, a particular individual's requirement for dose escalation may be due to tolerance, opioid-induced hyperalgesia, or a combination of both. In tolerance, there is a lower sensitivity to opioids, which occurs via two major theories: decreased receptor activation (desensitization of antinociceptive mechanisms), and opioid receptor down-regulation (internalization of membrane receptors). In opioid-induced hyperalgesia, sensitization of pronociceptive mechanisms occurs, resulting in a decrease in the pain threshold, or allodyna. Identifying the development of hyperalgesia is of great clinical importance since patients receiving opioids to relieve pain may paradoxically experience more pain as a result of treatment. Whereas increasing the dose of opioid can be an effective way to overcome tolerance, doing so to compensate for opioid-induced hyperalgesia may worsen the patient's condition by increasing sensitivity to pain while escalating physical dependence.

The phenomenon is common among palliative care patients following a too rapid escalation of opioid dosage.

Hyperpathia describes the neuropathic pain which the pain threshold on one hand is elevated and the other hand is central hyperexcited whenever there is a loss of fibres. Hyperpathia is underlying the peripheral or central deafferentation when the afferent inputs are lost. Hyperpathia only occurs on neuropathic pain patients with the loss of fibres.

The International Association of the Study of Pain’s (IASP) definition of hyperpathia is that: "A painful syndrome characterized by an abnormally painful reaction to a stimulus, "especially a repetitive stimulus, as well as an increased threshold." The definition also complies with a note which is: "It may occur with allodynia, hyperesthesia, hyperalgesia, or dysesthesia. Faulty identification and localization of the stimulus, delay, radiating sensation, and after-sensation may be present, and the pain is often explosive in character. The changes in this note are the specification of allodynia and the inclusion of hyperalgesia explicitly. Previously hyperalgesia was implied, since hyperesthesia was mentioned in the previous note and hyperalgesia is a special case of hyperesthesia".

Complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy (RSD), is a long term pain syndrome that often worsens with time. It is characterized by severe pain out of proportion to the original injury and is often accompanied by sensitivity, swelling, and changes in the skin. It may initially affect one limb and then spread throughout the body; 35% of affected people report symptoms throughout their whole body.

The cause of CRPS is unknown though CRPS is associated with dysregulation of the central nervous system and autonomic nervous system resulting in abnormal temperature control and pain of the affected limb(s) resulting in functional impairment and disability. Precipitating factors include injury and surgery, although there are cases where no identifiable injury had occurred at the original site. CRPS is not caused by psychological factors, yet the constant pain and reduced quality of life are known to cause psychological problems (such as increased depression and anxiety). Although "research does not reveal support for specific personality or psychopathology predictors of the condition," CRPS is associated with psychosocial effects, including impaired social and occupational function. It is classified as an amplified musculoskeletal pain syndrome.

Treatment involves a multidisciplinary approach involving medications, physical and occupational therapy, psychological treatments, and neuromodulation. Despite this, the results are often unsatisfactory, especially if treatment is delayed.

Affected individuals typically experience limited relief from standard pain relieving medication, with the exception of some neuroleptic agents. Patients frequently experience 'pseudovisceral' phenomena or symptoms of altered autonomic nervous system function including nausea, bloating, abdominal swelling, loss of appetite with consecutively lowered body weight or an altered defecation process.

Pain is typically related to tensing the abdominal wall muscles, so any type of movement is prone to aggravate pain. Lying quietly can be the least painful position. Most patients report that they cannot sleep on the painful side.

Anterior cutaneous nerve entrapment syndrome (ACNES) is a nerve entrapment condition that causes chronic pain of the abdominal wall. It occurs when nerve endings of the lower thoracic intercostal nerves (7–12) are 'entrapped' in abdominal muscles, causing a severe localized nerve (neuropathic) pain that is usually experienced at the front of the abdomen.

ACNES syndrome is frequently overlooked and unrecognized, although the incidence is estimated to be 1:2000 patients.

The relative unfamiliarity with this condition often leads to significant diagnostic delays and misdiagnoses, often resulting in unnecessary diagnostic interventions and futile procedures. Physicians often misdiagnose ACNES as irritable bowel syndrome or "functional disorders", as symptoms of the condition are not dispositive.

Tension-type headache pain is often described as a constant pressure, as if the head were being squeezed in a vise. The pain is frequently present on both sides of the head at the same time. Tension-type headache pain is typically mild to moderate, but may be severe.

According to the third edition of the International Classification of Headache Disorders, the attacks must meet the following criteria:

- A duration of between 30 minutes and 7 days.

- At least two of the following four characteristics:

- bilateral location

- pressing or tightening (non-pulsating) quality

- mild or moderate intensity

- not aggravated by routine physical activity such as walking or climbing stairs

- Both of the following:

- no nausea or vomiting

- no more than one of photophobia (sensitivity to bright light) or phonophobia (sensitivity to loud sounds)

Tension-type headaches may be accompanied by tenderness of the scalp on manual pressure during an attack.

Based on frequency, tension-type headaches can be sub-classified as

- Infrequent episodic: occurring less than once per month on average, or less than 12 episodes a year;

- Frequent episodic: occurring between 1-14 times per month on average for at least 3 months;

- Chronic: occurring 15 times a month for at least 3 months (CTTH - "chronic tension-type headache").

In examining the published studies on opioid-induced hyperalgesia (OIH), Reznikov "et al" criticize the methodologies employed on both humans and animals as being far-removed from the typical regimen and dosages of pain patients in the real world. They also note that some OIH studies were performed on drug addicts in methadone rehabilitation programs, and that such results are very difficult to generalize and apply to medical patients in chronic pain. In contrast, a study of 224 chronic pain patients receiving 'commonly-used' doses of oral opioids, in more typical clinical scenarios, found that the opioid-treated patients actually experienced no difference in pain sensitivity when compared to patients on non-opioid treatments. The authors conclude that opioid-induced hyperalgesia may not be an issue of any significance for normal, medically-treated chronic pain patients at all.

Opioid-induced hyperalgesia has also been criticized as overdiagnosed among chronic pain patients, due to poor differential practice in distinguishing it from the much more common phenomenon of opioid tolerance. The misdiagnosis of common opioid tolerance (OT) as opioid-induced hyperalgesia (OIH) can be problematic as the clinical actions suggested by each condition can be contrary to each other. Patients misdiagnosed with OIH may have their opioid dose mistakenly decreased (in the attempt to counter OIH) at times when it is actually appropriate for their dose to be increased or rotated (as a counter to opioid tolerance).

The suggestion that chronic pain patients who are diagnosed as experiencing opioid-induced hyperalgesia ought to be completely withdrawn from opioid therapy has also been met with criticism. This is not only because of the uncertainties surrounding the diagnosis of OIH in the first place, but because of the viability of rotating the patient between different opioid analgesics over time. Opioid rotation is considered a valid alternative to the reduction or cessation of opioid therapy, and multiple studies demonstrate the rotation of opioids to be a safe and effective protocol.

Tension headache, also known as tension-type headache, is the most common type of primary headache. The pain can radiate from the lower back of the head, the neck, eyes, or other muscle groups in the body typically affecting both sides of the head. Tension-type headaches account for nearly 90% of all headaches.

Pain medication, such as aspirin and ibuprofen, are effective for the treatment of tension headache. Tricyclic antidepressants appear to be useful for prevention. Evidence is poor for SSRIs, propranolol, and muscle relaxants.

As of 2013 tension headaches affect about 1.6 billion people (20.8% of the population) and are more common in women than men (23% to 18% respectively).

Non-dental causes of toothache are much less common as compared with dental causes. In a toothache of neurovascular origin, pain is reported in the teeth in conjunction with a migraine. Local and distant structures (such as ear, brain, carotid artery, or heart) can also refer pain to the teeth. Other non-dental causes of toothache include myofascial pain (muscle pain) and angina pectoris (which classically refers pain to the lower jaw). Very rarely, toothache can be psychogenic in origin.

Disorders of the maxillary sinus can be referred to the upper back teeth. The posterior, middle and anterior superior alveolar nerves are all closely associated with the lining of the sinus. The bone between the floor of the maxillary sinus and the roots of the upper back teeth is very thin, and frequently the apices of these teeth disrupt the contour of the sinus floor. Consequently, acute or chronic maxillary sinusitis can be perceived as maxillary toothache, and neoplasms of the sinus (such as adenoid cystic carcinoma) can cause similarly perceived toothache if malignant invasion of the superior alveolar nerves occurs. Classically, sinusitis pain increases upon Valsalva maneuvers or tilting the head forward.

Painful conditions which do not originate from the teeth or their supporting structures may affect the oral mucosa of the gums and be interpreted by the individual as toothache. Examples include neoplasms of the gingival or alveolar mucosa (usually squamous cell carcinoma), conditions which cause gingivostomatitis and desquamative gingivitis. Various conditions may involve the alveolar bone, and cause non-odontogenic toothache, such as Burkitt's lymphoma, infarcts in the jaws caused by sickle cell disease, and osteomyelitis. Various conditions of the trigeminal nerve can masquerade as toothache, including trigeminal zoster (maxillary or mandibular division), trigeminal neuralgia, cluster headache, and trigeminal neuropathies. Very rarely, a brain tumor might cause toothache. Another chronic facial pain syndrome which can mimic toothache is temporomandibular disorder (temporomandibular joint pain-dysfunction syndrome), which is very common. Toothache which has no identifiable dental or medical cause is often termed atypical odontalgia, which, in turn, is usually considered a type of atypical facial pain (or persistent idiopathic facial pain). Atypical odontalgia may give very unusual symptoms, such as pain which migrates from one tooth to another and which crosses anatomical boundaries (such as from the left teeth to the right teeth).

Establishing a diagnosis of nondental toothache is initially done by careful questioning about the site, nature, aggravating and relieving factors, and referral of the pain, then ruling out any dental causes. There are no specific treatments for nondental pain (each treatment is directed at the cause of the pain, rather than the toothache itself), but a dentist can assist in offering potential sources of the pain and direct the patient to appropriate care. The most critical nondental source is the radiation of angina pectoris into the lower teeth and the potential need for urgent cardiac care.

Apical abscesses can spread to involve periodontal pockets around a tooth, and periodontal pockets cause eventual pulp necrosis via accessory canals or the apical foramen at the bottom of the tooth. Such lesions are termed periodontic-endodontic lesions, and they may be acutely painful, sharing similar signs and symptoms with a periodontal abscess, or they may cause mild pain or no pain at all if they are chronic and free-draining. Successful root canal therapy is required before periodonal treatment is attempted. Generally, the long-term prognosis of perio-endo lesions is poor.

The pain is sharp and sudden, in response to an external stimulus. The most common trigger is cold, with 75% of people with hypersensitivity reporting pain upon application of a cold stimulus. Other types of stimuli may also trigger pain in dentin hypersensitivity, including:

- Thermal – hot and cold drinks and foods, cold air, coolant water jet from a dental instrument.

- Electrical – electric pulp testers.

- Mechanical–tactile – dental probe during dental examination, periodontal scaling and root planing, toothbrushing.

- Osmotic – hypertonic solutions such as sugars.

- Evaporation – air blast from a dental instrument.

- Chemical – acids, e.g. dietary, gastric, acid etch during dental treatments.

The frequency and severity with which the pain occurs are variable.

CVAC sessions

Cyclic Variations in Adaptive Conditioning (CVAC) is a method of touch free cyclic hypobaric pneumatic compression for treatment of tissue edema and, therefore, edema-associated pain. As a pilot study, 10 participants with AD completed pain and quality of life questionnaires before and after 20–40 minutes of CVAC process daily for 5 days. After treatment, there was a significant decrease in pain as measured by the Pain Catastrophizing Scale and the Visual Analogue Scale, but there was no change in pain quality by the McGill Pain Questionnaire. However, there were no changes in the Pain Disability Index or Pittsburgh Sleep Quality Index. This study suggests a potential treatment role for CVAC, and the authors recommended randomized controlled clinical trials.

Dentin hypersensitivity (abbreviated to DH, or DHS, and also termed sensitive dentin, dentin sensitivity, cervical sensitivity, and cervical hypersensitivity) is dental pain which is sharp in character and of short duration, arising from exposed dentin surfaces in response to stimuli, typically thermal, evaporative, tactile, osmotic, chemical or electrical; and which cannot be ascribed to any other dental disease.

A degree of dentin sensitivity is normal, but pain is not usually experienced in everyday activities like drinking a cooled drink. Therefore, although the terms "dentin sensitivity" and "sensitive dentin" are used interchangeably to refer to dental hypersensitivity, the latter term is the most accurate.

Acute inflammation is a short-term process, usually appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus. It involves a coordinated and systemic mobilization response locally of various immune, endocrine and neurological mediators of acute inflammation. In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases. It is characterized by five cardinal signs:

An acronym that may be used to remember the key symptoms is "PRISH", for pain, redness, immobility (loss of function), swelling and heat.

The traditional names for signs of inflammation come from Latin:

- Dolor (pain)

- Calor (heat)

- Rubor (redness)

- Tumor (swelling)

- Functio laesa (loss of function)

The first four (classical signs) were described by Celsus (ca. 30 BC–38 AD), while "loss of function" was probably added later by Galen. However, the addition of this fifth sign has also been ascribed to Thomas Sydenham and Virchow.

Redness and heat are due to increased blood flow at body core temperature to the inflamed site; swelling is caused by accumulation of fluid; pain is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings. Loss of function has multiple causes.

Acute inflammation of the lung (usually caused in response to pneumonia) does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings.

Inflammation (from Latin "") is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.

The classical signs of inflammation are heat, pain, redness, swelling, and loss of function. Inflammation is a generic response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, which is specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer (e.g., gallbladder carcinoma). Inflammation is therefore normally closely regulated by the body.

Inflammation can be classified as either "acute" or "chronic". "Acute inflammation" is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes (especially granulocytes) from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within the injured tissue. Prolonged inflammation, known as "chronic inflammation", leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.

Inflammation is not a synonym for infection. Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response — the two components are considered together when discussing an infection, and the word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation on the other hand describes purely the body's immunovascular response, whatever the cause may be. But because of how often the two are correlated, words ending in the suffix "" (which refers to inflammation) are sometimes informally described as referring to infection. For example, the word "urethritis" strictly means only "urethral inflammation", but clinical health care providers usually discuss urethritis as a urethral infection because urethral microbial invasion is the most common cause of urethritis.

It is useful to differentiate inflammation and infection as there are many pathological situations where inflammation is not driven by microbial invasion – for example, atherosclerosis, type III hypersensitivity, trauma, ischaemia. There are also pathological situations where microbial invasion does not result in classic inflammatory response—for example, parasitosis, eosinophilia.

Four cardinal symptoms have sometimes been used as diagnostic criteria:

1. painful, fatty lipomas (benign fatty tumors) across anatomy

2. obesity, frequently in menopausal age

3. weakness and fatigue

4. emotional instability, depression, epilepsy, confusion, and dementia.

There are also potential signs of the disease which are identified as the following:

However, as it is unclear which symptoms are cardinal and which symptoms are minor signs in Dercum's disease, it is unclear which should be used as diagnostic criteria. Researchers have proposed a 'minimal definition' based on symptoms most often part of Dercum's disease: 1) Generalized overweight or obesity. 2) Chronic pain in the adipose tissue. The associated symptoms in Dercum's disease include obesity, fatty deposits, easy bruisability, sleep disturbances, impaired memory, depression, difficulty concentrating, anxiety, rapid heartbeat, shortness of breath, diabetes, bloating, constipation, fatigue, weakness and joint and muscle aches. Regarding the associated symptoms in Dercum's disease, only case reports have been published. No study involving medical examinations has been performed in a large group of patients.

The sensation of itch can be reduced by many painful sensations. Studies done in the last decade have shown that itch can be inhibited by many other forms of painful stimuli, such as noxious heat, physical rubbing/scratching, noxious chemicals, and electric shock.

Itch can originate in the peripheral nervous system (dermal or neuropathic) or in the central nervous system (neuropathic, neurogenic, or psychogenic).

Functional gastrointestinal disorders are very common. Globally, irritable bowel syndrome and functional dyspepsia alone may affect 16–26% of the population.