Pain

From birth to losing a loved one, the experience of pain is central to human life. Indeed, it may be argued that people expend most of their time and effort in trying to avoid the pain of hunger, physical injury or emotional hurt. From this perspective, the phenomenon of pain has been the engine for much of technological progress and the advancement of civilisation. This article is a general introduction to the cycle of Citizendium articles on our current understanding of the phenomenon of pain, what it means, how it works, and where humanity may be heading in trying to come to terms with this most basic of experiences.

Description

Pain may be quantified on a pain numeric rating scale (NRS) that ranges from 1-10 points; however, the accuracy of such as scale (using a cut point of 4 or more) for predicting pain that interferes with functioning is:

• sensitivity 64%
• specificity 83%

The meaning of pain

The experience of pain is universally and intuitively recognised, but its definition remains controversial. Most people would consider that, by saying that they "have pain", and by giving some indication of where and how severe the hurt is, they are making their experience clear to the listener. The idea that such a subjective communication is the only way we have of knowing what the person is experiencing presents difficulties for those who wish to study pain from either a physical scientific or a philosophical perspective. The scientist and philosopher would like to be able to define the experience of pain, so that it can be analysed, discussed, researched, and understood. Without such an agreed definition, a Tower of Babel like confusion could result.

The difficulty is because pain is an observation about something that arises inside the sufferer's own body. This is very different from external sense experiences such as vision, hearing or taste, where the stimulus is a clearly definable physical or chemical entity, correlated in a specific way with the word that we use for our perception of that event (e.g. blue, G-flat, or sweet). For pain, the only objective enidence that might correlate with the reported experience is injury to body tissue, yet although an injury may be obvious to an observer, the feeling of pain is not. Pain may be deduced from physical observations, but can be confirmed only by the sufferer.

The International Association for the Study of Pain (IASP) recognised these enigmatic qualities when, in 1994, its committee on taxonomy formulated the IASP definition of pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. This definition applies to pain in humans only, as science cannot evaluate the emotions of animals. There are other definitions of pain, and recent advances in imaging of the brain in pain (e.g. fMRI, SPECT), as well as the identification of biochemical markers of nociceptor nerve activity (e.g. C-fos) may allow more specific descriptions of the phenomenon of pain. At present there is no consistent explanation for how and why people perceive pain in different situations, and in different ways. The idea that some anaesthetists propound that the stress response, spinal metabolic changes and autonomic changes are sufficient to diagnose "pain", when the person is under general anaesthesia, indicates that even in scientific circles there is no consensus about the difference between nociception and pain.

Nociceptive pain

See main article Pain physiology.

"Nociception is the term introduced almost 100 years ago by the great physiologist Sherrington (1906) to make clear the distinction between detection of a noxious event or a potentially harmful event and the psychological and other responses to it."

Nociception is also known as nociperception and physiological pain.

Pain often has a physical cause, an injury to the body outside of the nervous system. In these cases, pain is initiated by mechanical, thermal or chemical changes in non-nervous tissues; this causes activation of specific nerves which relay to spinal centres concerned with the detection of injury, and thence to the thalamus and cortex, as well as to the reticular system. This hard-wired injury detection mode for pain is called "nociception", meaning detection of harm, while the nerves which detect the damage are called nociceptor nerves ("nociceptors" for short).

Common causes of nociceptive pain include traumatic injury (fractures, torn tissue and burns), degenerative conditions such as osteoarthritis, infections and inflammatory conditions such as abscesses or sunburn, and cancers causing tissue breakdown.

Nociceptors (Pain receptors)

All nociceptors are free nerve endings 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 microscopically like the branches of small bushes. There are mechanical, thermal, and chemical nociceptors. They are found in skin and on internal surfaces such as periosteum and joint surfaces. Deep internal surfaces are only weakly supplied with pain receptors and will propagate sensations of chronic, aching pain if tissue damage in these areas occurs.

Two main types of nociceptor, Aδ and C fibres, mediate fast and slow pain respectively. Thinly myelinated type Aδ fibres, which transmit signals at rates of between 6 to 30 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 between 0.5 and 2 meters per second, is an aching, throbbing, burning pain. Chemical pain is an example of slow pain. Nociceptors 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.

Transmission of nociception (pain) signals in the central nervous system

There are 2 pathways for transmission of nociception in the central nervous system. 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 of the spinal cord. Second order neurons of the neospinothalamic tract then take off and give rise to long fibres which cross the midline through the grey commissure and pass upwards in the contralateral anterolateral columns. These fibres then terminate on the reticular formation,Ventrobasal Complex (VBC) of the thalamus. From here, third order neurons communicate with the somatosensory cortex. Fast pain can be localised easily if Aδ fibres are stimulated together with tactile receptors.

• Slow pain is transmitted via slower type C fibres to laminae II and III of the dorsal horns, 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 grey commisure, and traveling upwards through the anterolateral pathway. These neurons terminate widely in the brain stem, with one tenth of fibres stopping in the thalamus, and the rest stopping in the medulla, pons and tectum of midbrain mesencephalon, periaqueductal grey. Slow pain is poorly localized.

Consequences of nociception

When the nociceptors are stimulated they transmit signals through sensory neurons in the spinal cord. These neurons release glutamate, a major exicitory neurotransmitter that relays signals from one neuron to another.

If the signals are sent to the reticular formation of brain stem, thalamus, then pain enters consciousness, but in a dull poorly localised manner. From the thalamus, the signal can travel to the somatosensory cortex in the cerebrum, when the pain is experienced as localised and having more specific qualities.

Feinstein and colleagues found that nociception could also, "activate generalized autonomic responses independently of the relay of pain to conscious levels" causing "pallor, sweating, bradycardia, a drop in blood pressure, subjective "faintness," nausea and syncope" .

Analgesia

The gate control theory of pain, proposed by Patrick Wall and Ron Melzack, postulates that nociception (pain) is "gated" by non-nociception 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 nociception (pain) information.

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 nociception (pain) inhibitory neurons within the dorsal horns of the spinal cord, which act to inhibit nociception(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 endorphins. These receptors, which exist in a variety of areas in the body, inhibit firing of neurons that would otherwise be stimulated to do so by nociceptors.

Neuropathic pain

A second physical origin for pain is damage to the nociceptor nerves themselves; this is important because it is very difficult to treat, tends to be long standing, and may not be diagnosed easily. In these cases there is no damaged tissue, and no heat, pressure, or release of pain nerve stimulating chemicals at the site where the brain perceives the pain to be coming from, i.e. there is no actual or potential tissue damage in "the area which hurts". It is the spontaneous activity of the damaged and dysfunctional nerves which convey impulses to the spinal cord nociceptor nerve structures, and thence to the higher centres. This mode of the experience of pain is called neuropathic, implying pathology or disease of the nerves themselves. Neuropathic pain may follow injury to a nerve, occurring at the same time as a more general tissue injury, so that nociceptive and neuropathic pain may initially co-exist, the combination often changing to more "pure" neuropathic pain as the tissue injury heals, but the nerves remain dysfunctional. A nerve may be traumatically injured in isolation, or a more generalised nerve injury may result from metabolic diseases such as diabetes, the effects of alcohol abuse, or neurotrophic (nerve) infections such as shingles (Herpes zoster). During its normal development, the brain " learns" to associate the activity of a specific set of pain nerves with injury to a specific body part, so neuropathic pain is felt in the area that would normally be innervated by the damaged nerve, i.e. the person does not perceive the nerve itself to be sore.

Central pain

The third type of pain is caused by damage to the central nervous system, including the spinal cord, structures at the base of the brain (notably the thalamus) and the brain itself. While this may correctly be called neuropathic (pathology of nerve tissue), the clinical and prognostic implications of these pain states has lead to the term "central pain" being applied to these very stubborn pain syndromes. Examples of such syndromes include "spinal cord injury pain" and "post-stroke pain". The central nervous system itself is insensitive to pain (it does not contain nociceptor nerve fibres) and the pain is felt by the sufferer to be located somewhere else in the body, as is the case with peripheral nerve injury.

Pain syndromes

Some pain conditions are best described as "pain syndromes"; people with a specific pain syndrome share a defined set of symptoms and signs, the causes of which are poorly understood. Typically, pain syndromes are chronic painful diseases where there is much speculation about the mechanisms and interactions between mind, neuropathology and peripheral tissue abnormalities, and they can have a considerable impact on the sufferer's quality of life. Such syndromes include fibromyalgia syndrome, myofascial pain syndrome, complex regional pain syndrome, failed back syndrome, and post-whiplash injury syndrome.

Psychogenic pain

There is no consensus that psychogenic (in the sense of imaginary) pain exists. If someone were to experience pain as a result of a purely psychiatric disturbance, then presumably the central pain localising and "pain as suffering" paths of the brain would be activated just as in cases of "real" pain, making the condition subjectively indistinguishable from "real physical disease" pain. On the other hand, there are psychological disturbances where persons may complain of pain, act as if in pain, expect others to respond to them as if they are suffering pain, and are not experiencing pain as such, but another feeling such as stiffness or itch. Such illusions of pain are very rare. Because pain is apparently alike in all humans, this semantic error seldom occurs, and the clinical picture tends to be sufficiently inconsistent that the diagnosis would not be difficult to make after a period of conversation about the experience. It should be noted that a person who suffers hallucinations of pain (as opposed to illusions), is really experiencing pain (just as hallucinations of voices are real to the person), so that the complaint would then be consistent, and would need appropriate treatment to reduce the pain.

Finally, the issue of pain complaints as "malingering" remains a social, medical and legal problem. In the cases where the suffering of pain would lead to real benefits for the person, whether psycho-social or financial, involved persons tend to make the diagnosis without necessarily observing the course of the condition adequately. In clinical practice, malingering for financial or personal secondary gain reveals itself (if the person who complains is followed up adequately), as a pattern of inconsistent, irreconcilable, and conflicting actions and complaints. The psychological diagnosis of a "pain disorder" usually presents as persistent and excessive complaints of pain, with no obvious benefits to the person, but often associated with gross, persistent and intractable complaints about painful conditions which most people would consider minor.

Pain in animals

It is important to consider pain in animals for two quite different reasons. The first is the rather utilitarian consideration that most research that is done in an effort to advance our understanding and treatment of pain in humans is done on experimental animals. If animals do not experience pain as humans do, then this work would not be very helpful, but it is generally considered that the basic mechanisms of pain have been well conserved in the evolution of mammals, and so the mechanisms of pain are likely to be similar in laboratory rodents as in humans. The same is true to some extent also for Cephalopoda, although the pain sensing and processing systems differ in some respects from those of vertebrates

The second reason is that very many people accept that the relief of suffering is an obligation which we have not only to our own kind, but to a varying extent to the animals with which we share this world. In this regard, experimental work on pain, which uses animals as subjects, carries with it the obligation of high ethical standards. This research is important for example for the development of better analagesics and anaesthetics, and to develop treatments for chronic pain. At the same time, however, what is learned about the manifestations and treatment of pain in animals can also be used to help fellow living creatures who suffer pain - the very same species which are used for these experiments.

Treatment

Medications

Narcotics

Narcotics are commonly prescribed, and their usage may be increasing. In emergency rooms, non-Hispanic white patients are more likely to receive narcotics than patients of other ethnicities.

Narcotics are effective for both short (1-16 weeks) and long-term (6-24 months) use.

Narcotics, with long-term use, 80% of patients may have an adverse drug reaction, most commonly gastrointestinal. In addition, substrance abuse and "aberrant medication-taking behaviors" may occur. Advice for the treatment of acute pain among patients on chronic methadone is available.

Antidepressants

Antidepressants, especially tricyclic antidepressents, can help neuropathic pain according to a meta-analysis of randomized controlled trials by the Cochrane Collaboration.

Comparative studies

Regarding the treatment of chronic neuropathic pain in persons with spinal cord injury, a randomized controlled trial found that amitriptyline was more effective than active placebo and possibly better than gabapentin among patients with symptoms of depression while neither gabapentin nor amitriptyline helped patients without depression although there was a statistically insignificant trend favoring amitriptyline.

In a randomized controlled trial of patients with diabetic neuropathy, amitriptyline was better than fluoxetine In this trial, amitriptyline was effective in patients regardless of whether they had depression, whereas fluoxetine was effective only in depressed patients.

In a randomized crossover trial of patients with diabetic neuropathy, amitriptyline provided moderate or greater pain relief in 67% of patients as compared to 52% with gabapentin. In this small study, this result was statistically insignificant.

Other treatments

Humorous distraction may increase ability to tolerate pain.

Articles on pain

The reader is referred to the articles listed below - and to their sub-articles - for information on the different aspects of pain touched upon in this essay.

• Acute pain
• Back pain
• Biological pain markers
• Cancer pain
• Central pain
• Chronic pain
• Congenital absence of pain
• Definition of pain
• Diseases characterised by pain
• Economics of pain
• Headache
• Invasive pain treatments
• Neuropathic pain
• Nociceptive pain
• Pain and complementary and alternative medicine
• Pain and emotional suffering
• Pain and gender
• Pain and religion
• Pain and substance abuse
• Pain and placebo
• Pain assessment
• Pain biochemistry
• Pain clinics
• Pain genetics
• Pain imaging
• Pain in animals
• Pain in art and literature
• Pain in metabolic disease
• Pain in the child and fetus
• Pain in the older population
• Pain in the viscera
• Pain measurement
• Pain medications
• Pain physical treatments
• Pain physiology
• Pain rehabilitation
• Pain syndromes
• Pain treatment
• Pain, the state and civilization
• Pain: culture and ethnic factors
• Pelvic pain
• Philosophy of pain
• Psychology of pain
• Referred pain

Please add as required. Some could be fully self-sufficient articles, others sub-articles, others sections in an article. That can be sorted out as we get there. At this stage one would like to know that there is not some important aspect left out.

External links

• American Pain Society
• American Pain Foundation
• American Academy of Pain Management
• American Academy of Pain Medicine
• The British Pain Society
• The Society for Pain Practice Management
• The American Board of Pain Medicine
• The Physiotherapy Pain Association
• American Society of Pain Educators
• The Oxford Pain Internet Site
• American Chronic Pain Association
• American Society for Action on Pain