Pain

Pain is an unpleasant sensation that may be associated with actual or potential tissue damage and may contain physical and emotional components. Despite its unpleasantness, pain is a critical component of the human body's defense system. It is part of a rapid warning response instructing the motor neurons of the central nervous system to minimize perceived physical harm.

According to the International Association for the Study of Pain (IASP), pain and nociception are not the same. The term "pain" is a subjective experience that typically accompanies nociception, but can also arise without any stimulus, and thus it includes the emotional response. Nociception, on the other hand, is a neurophysiological term that denotes specific activity in nerve pathways. It is the transmission mechanism for physiological pain and does not describe psychological pain. These pathways transmit the nominally "painful" signals, though they are not always perceived as painful. Although pain can be associated with tissue damage or inflammation, this is not always the case.

Pain is a natural part of life and serves the important function of warning the individual organism to disengage from or address the harmful condition associated with the pain. Management of pain may be handled in various ways. Various drugs, such as acetaminophen or aspirin, can help dull or mask pain. There are many drug-free alternative medicines that have shown to be helpful in reducing pain as well, such as yoga, hypnosis, herbal remedies, and acupuncture. In some cases, a lifestyle change may be necessary to alleviate pain, as exemplified in a scenario wherein a headache was caused by some environmental or dietary factor, or was a poor response to stress.

In removing the warning sign of pain, it is important to identify and address the underlying cause rather than ignore it. Some causes of pain may be simple to diagnose like a scraped knee from a fall or a muscle ache from intense cardiovascular activity. Some pains may require a more comprehensive analysis, such as a pain in the side of the torso, which could be appendicitis, or an ache in the left shoulder, which could hint at a heart ailment.

Some individuals have the ability to control what and how they think when confronted with pain. Some practitioners of various religious disciplines have manifested a remarkable ability to control pain, or to replace pain with a sense of peace and tranquility.

Types of pain

Pain can be classified as acute or chronic.

Acute pain is defined as short-term pain or pain with an easily identifiable cause. It is the body's warning of disease or current damage to tissue. Acute pain often presents itself as fast and sharp and is usually followed by aching pain. Acute pain is centralized in one area before becoming somewhat spread out. This type of pain usually responds well to medications.

Chronic pain was originally defined as pain that lasts six months or longer. It is now defined as pain that persists longer than the normal course of time associated with a particular type of injury. This constant or intermittent pain has often outlived its purpose, as it does not help the body to prevent injury. It is often more difficult to treat than acute pain. Expert care is generally necessary to treat any pain that has become chronic. An anterior cingulectomy, neurosurgery that disconnects the anterior cingulate gyrus (part of the brain responsible for vocalizing the emotional and motoric functioning), can be used in extreme cases to treat chronic pain. As a result, patients still feel the sensation of pain minus the accompanying emotion post-surgery.

The experience of physiological pain can be grouped according to the source and related nociceptors, or pain detecting neurons.

Cutaneous pain is caused by injury to the skin or superficial tissues. Cutaneous tissue nociceptors terminate just below the skin, producing a well-defined, localized pain of short duration due to the high concentration of nerve endings. Examples of injuries that produce cutaneous pain include paper cuts, minor (first degree) burns, and lacerations (cuts).

Somatic pain originates from ligaments, tendons, bones, blood vessels, and even nerves themselves. It is detected with somatic nociceptors. The scarcity of pain receptors in these areas produces a dull, poorly-localized pain of longer duration than cutaneous pain. Examples of such pain include sprains and broken bones.

Visceral pain originates from the body's viscera, or organs. Visceral nociceptors are located within body organs and internal cavities. The even greater scarcity of nociceptors in these areas produces pain that is usually more aching and of a longer duration than somatic pain. Visceral pain is extremely difficult to localize, and several injuries to visceral tissue exhibit "referred" pain, where the sensation is localized to an area completely unrelated to the site of injury. Myocardial ischaemia, which is the loss of blood flow to a part of the heart muscle tissue, is possibly the best known example of referred pain. The sensation can occur in the upper chest as a restricted feeling or as an ache in the left shoulder, arm or even hand. Referred pain can be explained by the findings that pain receptors in the viscera also excite spinal cord neurons that are excited by cutaneous tissue. Since the brain normally associates firing of these spinal cord neurons with stimulation of somatic tissues in skin or muscle, pain signals arising from the viscera are interpreted by the brain as originating from the skin. The theory that visceral and somatic pain receptors converge and form synapses (junctions) on the same spinal cord pain-transmitting neurons is called Ruch's Hypothesis.

Phantom limb pain is the sensation of pain from a limb that has been lost or from which a person no longer receives physical signals. It is an experience almost universally reported by amputees and quadriplegics.

Neuropathic pain, or "neuralgia", can occur as a result of injury or disease to the nerve tissue itself. This can disrupt the ability of the sensory nerves to transmit correct information to the thalamus, and hence the brain interprets painful stimuli even though there is no obvious or known physiologic cause for the pain.

Physiology

Pain receptors

All pain receptors are free nerve endings, which means they are unspecialized nerve endings that bring information from the external environment to the central nervous system and brain.

Three types of pain receptors exist: mechanical, thermal and chemical. They are found in skin and on internal surfaces such as periosteum (tissue that covers bones) and joint surfaces. Deep internal surfaces are weakly supplied with pain receptors and will propagate sensations of chronic, aching pain if tissue damage in these areas is experienced.

Pain receptors do not adapt to stimulus. In some conditions, excitation of pain fibers becomes greater as the pain stimulus continues, leading to a condition called hyperalgesia.

Nociceptors are the free nerve endings of neurons that have their cell bodies outside the spinal column in the dorsal root ganglion and are named based upon their appearance at their sensory ends. These sensory endings look like the branches of small bushes.

Two main types of nociceptors, Aδ and C fibers, mediate fast and slow pain respectively. Thinly myelinated type Aδ fibers, which transmit signals at rates between six to thirty meters per second mediate fast pain. This type of pain is felt within a tenth of a second of application of the pain stimulus. It can be described as sharp, acute, pricking pain and includes mechanical and thermal pain. Slow pain, mediated by slower, unmyelinated ("bare") type C pain fibers that send signals at rates of between one-half to two meters per second, is an aching, throbbing, burning pain. Chemical pain is one example of slow pain.

Transmission of pain signals in the central nervous system

The perception of pain occurs when nociceptors are stimulated and transmit signals through sensory neurons in the spinal cord. These neurons release glutamate, a major excitory neurotransmitter that relays signals from one neuron to another. The signals are sent to the thalamus (part of brain), in which pain perception occurs. From the thalamus, the signal travels to the somatosensory cortex in the cerebrum, at which point the individual becomes fully aware of the pain. The cerebrum occupies most of the cranial cavity and is responsible for higher mental functions such as thought, emotion, reason, and memory. It also integrates sensory and motor functions.

There are two pathways for the transmission of pain in the central nervous system, or CNS. These are the neospinothalamic tract for fast pain and the paleospinothalamic tract for slow pain.

Fast pain travels via type Aδ fibers to terminate on lamina I (lamina marginalis) of the dorsal horn, which is part of the occipital division of the brain. Second order neurons of the neospinothalamic tract then take off and give rise to long fibers which cross the midline through the anterior commissure and pass upwards in the contralateral and anterolateral columns. These fibers then terminate on the ventrobasal complex (VBC) of the thalamus. From here, third order neurons communicate with the somatosensory cortex. The anterior commissure is a group of fibers that cross from one side of the brain to the other. Fast pain can be localized easily if Aδ fibers are stimulated together with tactile receptors.

Slow pain is transmitted via slower type C fibers to laminae II and III of the dorsal horn, together known as the substantia gelatinosa. Second order neurons take off and terminate in lamina V, also in the dorsal horn. Third order neurons then join fibers from the fast pathway, crossing to the opposite side via the anterior commissure, and travelling upwards through the anterolateral pathway. These neurons terminate widely in the brain stem, with one tenth of fibers stopping in the thalamus, and the rest stopping in the medulla, pons and mesencephalon (also known as the midbrain). Slow pain is poorly localized.

Analgesia

Analgesia is an absence of the sensation of pain while still being conscious. An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain and to achieve analgesia. Analgesic drugs act in various ways on the peripheral and central nervous system; they include acetaminophen (paracetamol), the nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and other salicylates, narcotic drugs such as morphine, synthetic drugs with narcotic properties such as tramadol, and various others.

The analgesia system is mediated by 3 major components: the periaquaductal grey matter (in the midbrain), the nucleus raphe magnus (in the medulla), and the pain inhibitory neurons within the dorsal horns of the spinal cord, which act to inhibit pain-transmitting neurons also located in the spinal dorsal horn.

The body has several different types of opioid receptors that are activated in response to the binding of the body's endogenous endorphins. The endogenous endorphins are dynorphins, endorphins, and enkephalins. These receptors, which exist in a variety of areas in the human body, inhibit firing of neurons that would otherwise be stimulated to do so by nociceptors.

The gate control theory of pain, proposed by Patrick Wall and Ron Melzack, postulates that pain is "gated" by non-painful stimuli such as vibration. Thus, rubbing a bumped knee seems to relieve pain by preventing its transmission to the brain. Pain is also "gated" by signals that descend from the brain to the spinal cord to suppress (and in other cases enhance) incoming pain information.

Survival Benefit

Despite its unpleasantness, pain is an important part of the existence of humans and other animals; in fact, it is vital to survival. Pain encourages an organism to disengage from the noxious stimulus associated with the pain. Preliminary pain can serve to indicate that an injury is imminent, such as the ache from a soon-to-be-broken bone. Pain may also promote the healing process, since most organisms will protect an injured region in order to avoid further pain. People born with congenital insensitivity to pain usually have short life spans and suffer numerous ailments, such as broken bones, bed sores, and chronic infection.

The study of pain has in recent years diverged into many different fields from pharmacology to psychology and neurobiology. It was even proposed that fruit flies may be used as an animal model for pharmacological pain research [1]. Pain is also of interest in the search for the neural correlates of consciousness, as pain has many subjective psychological aspects besides the physiological nociception.

Interestingly, the brain itself is devoid of nociceptive tissue and therefore cannot experience pain. Thus, a headache is not due to stimulation of pain fibers in the brain itself. Rather, the membrane surrounding the brain and spinal cord, called the dura mater, is innervated with pain receptors, and stimulation of these dural nociceptors (pain receptors) is thought to be involved to some extent in producing headache pain. Some evolutionary biologists have speculated that this lack of nociceptive tissue in the brain might occur as a result of any injury of sufficient magnitude to cause pain in the brain has a sufficiently high probability of being fatal and that development of nociceptive tissue would therefore have little to no survival benefit.

Since pain is defined as a signal of present or impending tissue damage affected by a harmful stimulus, the ability to experience pain or irritation is observable in most multicellular organisms. Even some plants have the ability to retract from a noxious stimulus. Whether this sensation of pain is equivalent to the human experience is debatable.

Chronic pain, in which the pain becomes pathological rather than beneficial, is an exception to the idea that pain is helpful to survival. Furthermore, it is not clear what the survival benefit of sometimes extreme forms of pain (e.g. toothache) might be. Thus, the intensity of some forms of pain (for example as a result of injury to fingernails or toenails) seem to be out of proportion with any survival benefits.

Sensitivity to pain

Sensitivity to pain varies among individuals (Skovlund et al. 2005; Coghill et al. 2003). Factors such as obesity and even hair color has been shown to correlate with pain sensitivity as well. Liem et al. (2005), for example, performed an experiment from which they deduced that redheads are more sensitive to thermal pain and are resistant to the analgesic effects of subcutaneous lidocaine.

Children have been proven to be markedly more sensitive to pain, but this fact is commonly dismissed as a fear reaction or a lack of coping abilities. Research has been carried out on how children can cope with pain due to increased sensitivity and it has been established that strategies that remove pain can help prevent long-term increases in sensitivity as the nervous system is still developing.

Pain and Alternative Medicine

A recent survey by the United States National Center for Complementary and Alternative Medicine, also known as NCCAM, found that pain was the most common reason people use complementary and alternative medicine (CAM). Among American adults who used CAM in 2002, 16.8 percent used CAM to treat back pain; 6.6 percent for neck pain; 4.9 percent for arthritis; 4.9 percent for joint pain; 3.1 percent for headaches; and 2.4 percent used CAM to treat recurring pain. Some survey respondents may have used CAM to treat more than one of these pain conditions.

One such alternative traditional Chinese medicine, views pain as a "qi blockage" equivalent to electrical resistance, or as "stagnation of blood"—theorized as dehydration inhibiting metabolism. Traditional Chinese treatments such as acupuncture are considered to be more effective for non-traumatic pain than traumatic pain.

References
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Coghill, R. C., J. G. McHaffie, and Y.-F. Yen. 2003. Neural correlates of interindividual differences in the subjective experience of pain. Proceedings of the National Academy of Sciences 100(14):8538-8542.
International Association for the Study of Pain. IASP pain glossary A sample list of frequently used terms from H. Merskey and N. Bogduk (Editors), IASP Task Force on Taxonomy. 1994. Classification of Chronic Pain, Second Edition. Seattle: IASP Press.
Liem, E. B. T. V. Joiner, K. Tsueda, and D. I. Sessler. 2005. Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads. Anesthesiology 102(3):509-14.
Reinberg, S. 2006. Obese People Might Be More Sensitive to Pain. Physical factors may combine to increase sensitivity, researchers say. Healthday, March 1. 2006.
Slovlund, E., M. Bretthauer, T. Grotmol, I. K. Larsen, and G. Hoff. 2005. Sensitivity of pain rating scales in an endoscopy trial. Clinical Journal of Pain 21 (4): 292-296.

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