Hypoalgesia or hypalgesia denotes a decreased sensitivity to painful stimuli. Hypoalgesia occurs when

nociceptive Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an org ...

(painful) stimuli are interrupted or decreased somewhere along the path between the input (

nociceptors A nociceptor ("pain receptor" from Latin ''nocere'' 'to harm or hurt') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sens ...

), and the places where they are processed and recognized as

pain Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

in the conscious mind. Hypoalgesic effects can be mild, such as massaging a stubbed toe to make it hurt less or taking aspirin to decrease a headache, or they can be severe, like being under strong anesthesia. Hypoalgesia can be caused by exogenous chemicals such as

opioids Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

, as well as by chemicals produced by the body in phenomena such as fear- and exercise- induced hypoalgesia. Hypoalgesia can also be associated with diseases, such as CIPA or in less severe cases with

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

or other diseases associated with

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

Chemical causes

Analgesics

Analgesics are a class of biochemicals that cause hypoalgesia. Analgesics can act on both the

peripheral A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by the ...

and

central Central is an adjective usually referring to being in the center of some place or (mathematical) object. Central may also refer to: Directions and generalised locations * Central Africa, a region in the centre of Africa continent, also known as ...

nervous systems to decrease pain. Certain analgesics also work to decrease the source of the pain by working to decrease swelling and inflammation, as in the case of NSAIDs.

Opioids

Opioids refers to a specific group of analgesics – including

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

, and

opium Opium (or poppy tears, scientific name: ''Lachryma papaveris'') is dried latex obtained from the seed capsules of the opium poppy ''Papaver somniferum''. Approximately 12 percent of opium is made up of the analgesic alkaloid morphine, which i ...

– that act on

opioid receptor Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin r ...

s, which are located mainly in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

. Endogenous opioids are types of opioids produced by the body specifically to modulate pain. They include

endorphins Endorphins (contracted from endogenous morphine) are chemical signals in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in an area of the brain known as the pituitary gland. Hist ...

enkephalins An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin ...

dynorphins Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, a ...

and

endomorphins Endomorphins are considered to be natural opioid neurotransmitters central to pain relief. The two known endomorphins, endomorphin-1 and endomorphin-2, are tetrapeptides, consisting of Tyr-Pro-Trp-Phe and Tyr-Pro-Phe-Phe amino acid sequences respe ...

. These peptides are especially important for modulating pain in response to the environment. These can be released in response to a number of things, including increased blood pressure, pain and danger. It has been found that endogenous opioids are at least partially responsible for phenomena like "

Runner's high The neurobiological effects of physical exercise are numerous and involve a wide range of interrelated effects on brain structure, brain function, and cognition. A large body of research in humans has demonstrated that consistent aerobic exerci ...

", hypoalgesia in the fight-or-flight response, and even for the analgesic effects of acupuncture therapy. In all these cases, there is a certain level of signal processing that occurs in the CNS which leads to the release of these chemicals.

Exercise-induced hypoalgesia

There has been a great deal of research examining the link between exercise and hypoalgesia. Many studies have shown the direct link between the two by subjecting patients to exercise and rating their pain responses, but despite the great deal of research, the mechanism of action is still poorly understood. It has been shown that the triggering mechanism for the hypoalgesic effects is caused by the increase in blood pressure that accompanies a good workout. The body senses the increased blood pressure, and it is hypothesized that in response, endogenous opioids are released. This hypothesis is well supported in human research, and it has been verified that it plays a part, but animal research implies that other mechanisms are also involved such as the endocannabinoid system.

Fear-induced hypoalgesia

Fear induced hypoalgesia is another example of a mechanism controlled by opioids. It is postulated that fear is a defense mechanism that has evolved over time to provide protection. In the case of hypoalgesia, a decreased response to pain would be very beneficial in a situation where an organism's life was at stake, since feeling pain would be a hindrance rather than a help. It has been well documented that fear does cause a decrease in pain response, however much like the exercise induced hypoalgesia, the exact mechanisms of action are not well understood. Studies have shown that opioids are definitely involved in the process, yet opiates alone do not completely explain the analgesic response. What the other mechanisms of action are is still unknown.

Diseases

It has been demonstrated that many diseases can cause hypoalgesia. Some diseases, like CIPA, are hereditary disorders where genes essential for the correct functioning of

no longer work. There are many diseases like this, and they all fall under the category of hereditary sensory autonomic neuropathies. Alternatively, some diseases affect other functions in the body, which can activate the pathways that cause hypoalgesia. This effect happens in people with

and other diseases associated with

Hereditary neuropathies

Hereditary sensory and autonomic neuropathies (HSAN), e.g. CIPA, are hereditary disorders that are characterized by malfunctioning or nonfunctioning pain receptors. Most of these diseases are also associated with decreased temperature sensation as well. In some cases, these diseases are also associated with other symptoms like intellectual impairment and diminished production of sweat and tears. Diseases like this can be very dangerous for the patients, because they are not able to judge what hurts, and therefore when they should stop doing something. A child with the disease might bite their finger clean off before they realized that what they were doing might harm them, or they might leave their hand on a hot stove without ever realizing it was on. These examples support the theory that pain is essential for life, more specifically, survival.

Hypoalgesia and hypertension

Some studies have shown that

in patients can cause hypoalgesia.Edwards, L., C. Ring, et al. (2007). "Nociceptive flexion reflex thresholds and pain during rest and computer game play in patients with hypertension and individuals at risk for hypertension." ''Biol Psychol'' 76(1-2): 72–82. Diseases like

, which are associated with hypertension are also associated with hypoalgesia, however this is due to

diabetic neuropathy Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...

. Just like in Exercise-Induced Hypoalgesia, the increased blood pressure of hypertension works as a signal to the body to release opioids and activate other pain modulation pathways. Also, although the area is not widely studied, there is evidence that this is not the only cause. Diseases may lead to activation of any of these mechanisms, just like diabetes causing hypertension. A full study of the pathways regulating pain is needed.

References

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