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Inhibitory effects are achieved through the descending pathways, which reach from the conscious brain down to the gates in the subconscious brain and the spinal cord. The reason for this is that the gates are places where the flow of pain messages can be controlled or influenced (Wells & Nown 1998). By sending responses back to the periphery, the brain can ordered the release of chemicals that have analgesic effects, which can reduces or inhibit pain sensation. Pain generally starts with a physical event; a cut, burn, tear, or bump (Catalano, 1987). The sensation of pain usually depends on the activation of a set of neurons that includes primary afferent nociceptors, interneurons in the spinal cord, cells of the ascending tracts, thalamic neurons and neurons of the cerebral cortex. Hence, the pain system involves a set of ascending pathways that convey nociceptive information from peripheral nociceptors to higher levels of the central nervous system, as well as descending p athways that modulate that information (Bromm & Desmedth, 1995). The term nociception refers to the process by which pain information is carried from the periphery sense receptors in the skin and in the viscera to the cerebral cortex through network of neuronal relays (Karoly & Jensen 1987). Exteroceptors on the body surface and propioceptors within the body are specialized neurons that receive stimulation; mechanical (e.g. pressure), chemical, electrical, or thermal (i.e. hot -cold sensitive). The body is equipped with mechanical nociceptors at the periphery (so -called first-order neurons), which project to second -order neurons in the spinal cord and medulla, which then carries the sensory information (in the form of electrical impulse) to the thalamus, whe re it synapses with third-order neurons that transmit the impulse to the cortex. Second-order neurons sends their sensory inputs to the thalamus via two ascending pathways: the dorsal column medial -lemniscal system and the anterolateral system (includes the spinothalamic, spinoreticular, and spinotectal fibers). The former transmits impulse involving position sense, touch, and pressure. The latter pathway is involved in pain transmission (Karoly & Jensen 1987). The spinal cord is the central concourse alon g which all pain messages travels to and from the brain (Catalano, 1987). For example, when you stub your toe and your peripheral nerves register alarm, this acute pain is immediately relayed along the nerve fibers of your foot and leg to the substantia ge latinosa located within the dorsal horn of the spinal cord. The cells in the substantia gelatinosa relay this "fast pain" message along the neospinothalamic and terminating in the thalamus and the cortex (see diagram 4) (Catalano, 1987). The cortex is the region in which thoughts are processed. In contrast, chronic pain moves along a different and slower tract, called the paleospinothalamic tract. This "slow pain" is generally dull, aching, burning, and cramping (Catalano, 1987). Slow pain follows the same path as the fast pain through the spinal cord, but once in the brain, it separates and terminate in the hypothalamus and the limbic structures (Catalano, 1987). The hypothalamus is responsible for stimulating the release of stress hormones. The limbic structures are the places where emotions are processed. Just as there is an ascending pain pathway from the body to the brain, there is a descending pathway that allows the brain to modulate pain sensory. The brain uses this pathway to send chemical substances and nerve impulses back down to the cells in the spinal cord to act
Consultant. FRCS. such as the raphe nuclei. see Willis 1982. and various regions of the medullary reticular formation (for review. as well as sites in the hypothalamus. and sensorimotor cortex (Zimmerman 1984). 1983. Wells & Nown. descending inhibitory processes have been investigated in anesthetized animals (Zimmerman 1984).against the pain message sent up by the pain receptors. MD. Mokha 1983. orbital cortex. what their normal physiological functions are. Gebhart et al. For instance. . Disability Assessment Services. it has been extensively studied by scientists. Founder and at that time Head of the School of Anatomy. held in Waterloo 29/11/1996. Morton et al. Inc. It was found that the firing of dorsal horn neurons in response to noxious skin heating can be inhibited by stimulation in the periaqueductal gray (PAG) and the lateral reticular formation (LRF) in the mid brain. 1998). At the present it is not clear to what extent these different descending systems coo perate and interact. Anatomy of Pain This paper was presented at the Ontario Inter-Urban Pain Conference. inhibition of the spinal cord neurons can also be achieved by electrical stimulation in other regions of the brain. Hence. 1984). Descending inhibitory processes are of great interest in the research arena. This topic is updated from time to time. by Don Ranney. 1987. Orthopaedic Medicine and President. and how they can be activated other than by focal electrical stimulation. septum. In addition. Hence. the locus coeruleus. the primarily role of the descending pathway is to send chemical messages from the brain to close the gates in the spinal cord to ascending messages (Catalano. University of Waterloo.
I have found it helpful to think of pain as being peripheral or central in origin. Pain originating in the peripheral nerves. via trauma to the nerves. with the implication that much that hurts may be ignored. is neurogenic pain. Some of this may arise due to maladaptive thought processes. Pain is "an unpleasant sensory and emotional experience associated with actual or potential tissue damage. and primarily in the past half century. It involves sensitivity to chemical changes in the tissues and then interpretation that such changes are. By this I mean that its significance is determined by the cerebral cortex in the light of other activity there. whether or not harm has occurred or is occurring. a "primary" CNS dysfun tion.As the first presenter at a conference on The Interaction between Mind and Body. Pain may be classified in many ways. Cognition is involved in the formulation of this perception. This perception is real. Central pain arises from central nervous system pathology . But MOST of it is due to . true "psychogenic" pain. I must begin with a definition of pain and a brief discussion of types of pain. This is now known to be a false distinction.e. or in the peripheral nerves themselves. or described in terms of such damage" (Merskey. but still we hear today the concept of hurt being not the same thing as harm. and the Perception of Pain. The International Association for the Study of Pain has published the following definition of pain which reflects what has been learned about pain in the last four centuries. or may be harmful. From this definition we see that pain is a perception in the same way that vision and hearing are. tendons. i. etc. There are emotional consequences. and behavioral responses to the cognitive and emotional aspects of pain. What is Pain? Four centuries ago Descarte described pain in terms of an alarm bell ringing in a bell tower.. As a clinician dealing with soft tissue trauma. 1986). From this came the concept that there can be false alarms and we have therefore come to distinguish "psychogenic pain" from "real pain". Peripheral pain originates in muscles...
that distinguishes between normally functioning nerves and nerves whose function has been altered by pathology is as follows: y Nociceptive pain is pain in which normal nerves transmit information to the central nervous system about trauma to tissues (nocere = to injure.. multiple sclerosis. It travels to the spinal cord or brainstem as a train of electrical impulses in C fibres or A delta fibres of spinal or certain cranial nerves. signal passes once more electrically to higher CNS levels in Nociceptive Specific. We shall examine in turn peripheral nerve sensitivity. supraspinal modulation of the nociceptive signal. "Neuropathic" should not be confused with "neurogenic". The IASP defines central pain as "pain initiated or caused by a primary lesion or dysfunction in the central nervous system" (Merskey. y Neuropathic pain is pain in which there are structural and/or functional nervous system adaptations secondary to injury. may persist because of a Central Nervous System dysfunction. 1996). Much of what has previously been considered psychogenic pain is now better understood as neuropathic pain of central origin. 1994).structural changes in the CNS. 1996). dorsal horn pathophysiology. dorsal horn transmission. After crossing the synaptic junct ion through an extremely complex series of chemical interactions the. or less pain specific Wide Dynamic Range neurons. ascending . With this introduction we can now begin to follow the pathways by w hich information is transmitted centrally and is ultimately perceived as pain.g. Another classification. e. But this is a CNS dysfunction secondary to long continued peripheral pain. as well as in those with long continued pain for other reasons. Latin). that take place either centrally or peripherally (Jensen. stroke and epilepsy (Boivie. and Bogduk. The persistent pain often experienced in chronic work-related musculoskeletal injuries. spinal cord injury. a term used to describe pain resulting from injury to a peripheral nerve but without necessarily implying any "neuropathy".
and it is known to be produced on the other side of the synapse in addition to many other places. Vancouver. Peripheral Nerve Sensitivity Tissue damage results in a drop in pH and release of chemicals. calcitonin gene related peptide (CGRP). Fitzgerald and Woolf (1984) have hypothesized that C fibres are primarily chemical sensors. in addition to releasing substance P. histamines and bradykini.e. While doing so we should keep in mind an expression of Dr Ken Casey.82). thromboxane. although they do respond also to high level mechanical and thermal stimulation. nitric oxide (see Jensen. Neurotransmission is extremely complex involving: y y all six layers of the dorsal horn (primarily layers one. and a gas. Even chemical products of tissue breakdown may sometimes enter the neuron and be transported centrally to exert an effect at the dorsal horn synapse. Dorsal Horn Transmission At the dorsal horn. C fibres release other excitatory neurotransmitters: glutamate. August 1996). and five) influx of sodium and calcium ions from the interstitial spaces and outflow of potassium ions from within the nerve cell. "Nociception is born in the dorsal horn. This is referred to as peripheral sensitization in contrast to central sensitization which occurs at the dorsal horn.pathways. fig. The C fibres respond by generating an electrical impulse which travels along the nerve to the dorsal horn of the spinal cord. 1996. Substance P may also be released peripherally with resultant increase in peripheral vasodilation and further sensitization of the C fibre's peripheral ending. There is some confusion over nitric oxide.. to which small non-myelinated C fibres are sensitive.1. and leucotrienes in the damaged tissues. two. Its exact role remains to be fully defined. prostaglandins. but we don't call it pain till it reaches the brain" (IASP Conference. 5-hydroxy tryptamine). .g. aspartate. p. Both occur in chronic pain. and cortical reception areas involved in pain perception. e. Activity of the C fibres may be up -regulated peripherally by serotonin (i.
continue to view pain as Descarte did. spinothalamic or spinoreticular) neurons that arise in the dorsal horn. For further information see Jensen (1996). changes in expression of genes (e. p. This structural reorganization in the spinal cord's dorsal horn is one factor that can explain "abnormal" spread of pain that is still referred to as "psychogenic" by those who.g. These genetic changes affect the volume and type of enzymes and neuropeptides produced.y temporal summation. is the focus of much current research. the post-synaptic electrical discharge becomes more prolonged.c -fos and c-jun) occurs within the secondary (e. nearly four centuries later. with consequent increase in the severity of the pain.But many are structural in nature. the circumstances under which they occur. It is at this level that encephalin-producing descending fibres from the brain stem interact with both pre-synaptic and post-synaptic cells to inhibit transmission.This temporal summation is termed "windup". as well as how to prevent and even reverse them. To explore further the relationship be tween windup and central sensitization see Price (1999). and is given to stimulate further reading. Also at this level.g. at what has been called the "pain gate" by Melzack and Wall. Incoming fibres from a particular area are able to gain acces s to neurons ascending to conciousness that normally just carry information from areas some distance away. y Central sensitization is characteristic of chronic pain. incoming signals in the A beta fibres of a peripheral nerve can alter sensitivity of the post-synaptic cells to painful stimuli arriving in C and A delta fibres. involving . Dorsal Horn Pathophysiology Neuropathic changes can occur.. The following is by no means a complete description. Thereby they induce long term changes in these post-synaptic cells.90 -96. With long continued stimulation. If a stimulus arrives at the synapse in t he dorsal horn more frequently than once every 3 seconds. especially when pain persists. The nature of these. One of these changes is that nerve growth factor begins to be produced in sufficient quantities as to promote alteration in patterns of nerve connections in the dorsal horn of the spinal cord at or about the level of incoming pain fibres. there are physio logical changes. For example. y competition for opporunities to stimulate ascending pathways..
1996). So it should not surprise us that there are mechanisms to draw our attention to a source of pain. This mechanism may also be involved in the spread of pain perception beyond the area of injury. with consequent increase in inflammation. For example. but research continues daily to bring us more information. After a few days. y Volume transmission is the extrasynaptic spread of neuroactive molecules well beyond their target sites. These can increase or decrease the amount of pain. Yet pain is intended to tell us when something needs to be done about a damaged area. there is hyperalgesia well beyond this area. it also sends a retrograde electrical impulse which discharges substance P peripherally into the tissues. have shown similar effects when the sciatic nerve is stimulated after the gastrocnemius -soleus muscle in rats has become inflammed.different levels of the spinal cord (Jensen. y Dorsal ganglion reflexes may be generated. Much less is known about them than about lower level CNS changes. members of t he same team. as when fleeing from danger. y Several supraspinal pain modulating loops exist. and others to help us overlook it. but some may facilitate pain perception. This not only reinforces the incoming stimulus. even in the area supplied by the femoral nerve. The brain is supposed to help us sort out whether to pay attention to the painful area or ignore it. after crushing the sciatic nerve in rats there is initially hyperalgesia ( an exaggerated response to painful stimuli) in the skin supplied by the sciatic nerve. Supraspinal Modulating Loops Inhibition of pain is essential at times when safety is more important. Hoheisal et al (1994) and Mense et al (1997). y Other descending anatomical pathways exist that are primarily inhibitory. as a treatment of chronic pain. Cognitive Behavioral Therapy. Under certain conditions there can be reflex activation of the incoming sensory fibre. These substances may lead to long term potentiation of primary afferent neurotransmission and lasting changes in both neuronal excitability and gene expression. makes use of the following . These and the supraspinal modulating loops will now be briefly described.
There are pharmacological as well as anatomical distinctions between them. 4. many of which are called antinociceptive because they carry stimuli that inhibit pain perception.anatomical pathways. It is now known there are at least five on each side. Other Descending Pain Modulating Pathways These arise in the: y o o o y o o y o cerebral cortex and pass to the nucleus gracilis and cuneatus reticular formation thalamus periaqueductal grey matter and pass to the dorsal horn directly raphe nuclei of medulla. 2. and then to dorsal horn locus ceruleus and pass to the dorsal horn of spinal cord Spinocerebral Ascending Pathways . It was assumed there was one spinoreticular/reticulospinal loop on each side of the body. that these pass information in both directions. the dorsolateral pontine tegmentum the rostral ventral medulla the dorsal medulla the caudal medulla the lateral hypothalamus The effect of stimulating some of these centres can last from an hour to several days. It has been known for some time that the reticular formation of the brain stem is involved in either facilitation or inhibition of percep tion of pain under the influence of cortico-reticular signals. 5. and may be inhibitory or facilitatory. They connect the spinal cord to the following areas of the brainstem: 1. 3.
which in turn projects to the amygdala. . 1996 ).. This nucleus is subdivided for specific areas of the body. and feelings about it. Now this is known to be so (Hirshberg. or related to. 2. 1. lips. engages "the mind".g. we could say. This may be the same as. intracranial blood vessel tongue and cornea directly to the hypothalamus. The spinothalamic pathway crosses the midline and ascends on the opposite side of the spinal cord to the ventral posterolateral nucleus of the thalamus. and each area projects to its own section of the primary sensory cortex -. and other limbic system stuctures in the forebrain. 4.This discriminative pathway transmits to conciousness precise information about the location of pain. The spinoreticular pathway ascends on both sides of the spinal cord to the intralaminar nuclei of both the right and left thalamus. the amygdala ( memory a nd emotion ). hypothalamus. Clearly there is one pathway that is concerned with a discriminative analysis of pain. while the others involve the whole person.a thin band of cortex in the parietal lobe just posterior to the central sulcus. It carries information of emotional significance from the skin. 5. or earlier suggested and only recently accepted by all. and hypothalamus ( emotion and the vascular response to emotion ). 3. One.The first two have been well recognized for many years. sex organs. e. whose complexity makes them harder to define. but many others that concern our reactions to it. gastrointestinal tract. the anterior part of the cingulate gyrus ( emotion ). The spinomesencephalic tract has been described travelling with the spinotectal tract to the periacqueductal grey matter and superior colliculus of the midbrain. There may yet be others. The others have more recently been described. From there the next neuron in the chain takes the information to many areas of the brain. The dorsal column pathway has long been suspected of transmitting visceral nociception to the thalamus (as well as som atic touch and position sense). et al. The spinohypothalamic pathway is a very recently described route which does not synapse in the reticular formation. Unofficially I like to call it the "suffering" pathway. the pathway travelling to the parabrachial nucleus in the brainstem -.
.... sensory and motor cortex areas.. red nucleus......and in turn be affected by each and all of them.. 6....1996)..(14) occipital cortex..... amygdala......................(1 -4) premotor cortex ( for planning of movement )...Is there a "Cortical Pain Centre"? Unfortunately there is no discrete centre where pain is recognised.(6) other parts of the parietal cortex...... ......... But there is no one centre "in control"........ Therefore it is not surprising that PET scan data obtained during painful stimulation indicates activity in the following cortical areas.................... 1................(7 and 37 -40) other parts of the frontal cortex... movements and behaviour -.(19) Pain also projects to the following subcortical structures: thalamus.. Pain involves cognition................... putamen...... Pain is so important to survival that almost the whole brain is involved.........(8 -10 and 43-47) cingulate cortex..... hippocampus..... emotion.......................... 4.... Brodmann's tissue classification follows in brackets................ caudate nucleus....... affecting our thoughts and memories. attitutudes and emotions............. pulvinar...(24 and 32) insula... periaqueductal grey matter........... and vermis of the cerebellum (Wall........................... 7.......... Rather we see that pain can be all -pervasive....... and behaviour......... All of this supports Dennis Turk's claim that "the reign of pain is mainly in the brain".................... 5... hypothalamus....... 3......... 2..............
Salvage therapy is a form of treatment given after an ailment does not respond to standard treatment In oncology. or any treatment given after recurrence of a tumor. . a final treatment given after a tumor has not responded to other treatments.
 It is this part of the bone that grows during childhood. At roughly 18 to 25 years of age. as it grows. .The metaphysis is the wider portion of a long bone adjacent to the epiphyseal plate. it ossifies near the diaphysis and the epiphyses. the metaphysis stops growing altogether and completely ossifies into solid bone.
Xeroderma pigmentosum. the epiphysis is covered with articular cartilage. The diaphysis is the main or mid section (shaft) of a long bone. at its joint with adjacent bone(s).  If left . Between the epiphysis and diaphysis (the long midsection of the long bone) lies the metaphysis. The most common defect in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair (NER) enzymes are mutated. The epiphysis is filled with red bone marrow. which produces erythrocytes (red blood cells). no matter how small. It is made up of cortical bone and usually contains bone marrow and adipose tissue (fat). below that covering is a zone similar to the epiphyseal plate. Multiple basal cell carcinomas (basaliomas) and other skin malignancies frequently occur at a young age in those with XP. is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient. :574 In extreme cases all exposure to sunlight must be forbidden. At the joint.Epiphyseal plates ("growth plates") are located in the metaphysis and are responsible for growth in the length of the bone. or XP. In fact. leading to a reduction in or elimination of Nucleotide Excision Repair. The epiphysis is the rounded end of a long bone. known as subchondral bone (see Wiktionary:subchondral ). including the epiphyseal plate (growth plate). metastatic malignant melanoma and squamous cell carcinoma are the two most common causes of death in XP victims. XP is roughly six times more common in Japanese people than in other groups.
 . and skin cancers Eyes that are painfully sensitive to the sun and may easily become irritated. and ligase "seals" the transaction. namely CPDs (cyclobutane-pyrimidine-dimers) and 6-4PPs (pyrimidine-6-4-pyrimidone photoproducts). the result may be cancer. and clouded y y y y y y Blistering or freckling on minim um sun exposure Spidery blood vessels Oozing raw skin surface Limited growth of hair on chest and legs Scaly skin Irregular dark spots on the skin  Treatment The most obvious. In a healthy. such as basal cell carcinoma. Normally. bloodshot. the damage is first excised. DNA polymerase then repairs the missing sequence. normal human being. "cut out" by endonucleases. for this reason. Often occurring during a child's first exposure to sunlight. Keratoses can also be treated using cryotherapy or fluorouracil. Patients with XP are at a high risk for developing skin cancers. If tumour suppressor genes (e. damage caused by UV light can cause mutations in individual cells DNA. p53) or proto oncogenes are affected. This process is known as nucleotide excision repair Symptoms Some of the most common symptoms of XP include: y A severe sunburn when exposed to only small amounts of sunlight.g.unchecked. and often important part of treatment is avoiding exposure to sunlight. damage to DNA in epidermal cells occurs during exposure to UV light. y y y Development of many freckles at an early age Rough-surfaced growths (solar keratoses). The absorption of the high energy light leads to the formation of pyrimidine dimers.
malignancy develops in 2% Surgical pathology A proliferation of thin epithelium overlying papillary fibrovascular fronds.3¼4 of Pts also had HPV types 6 and 11 and upper respiratory tract lesions fibroepithelial papilloma a type containing extensive fibrous tissue. urethra or stratified cuboidal epithelium ² paranasal region. Prognosis Fewer than 40% of individuals with the disease survive beyond age 20 years. found in either transitional epithelium²renal pelvis. ureters. which recurs in ± 2¼3 of cases. . however inverted papilloma ENT An inverted or exophytic tumor of nasal cavity and paranasal sinuses. Some XP victims with less severe cases of the disease do manage to live well into their 40's. bladder.
y Others have them in many bones (polyostotic fibrous dysplasia). but not necessarily. often with a serous or bloody nipple discharge. . intraductal papilloma a tumor in a lactiferous duct. or multiple. y Many patients have lesions localized in only one bone ( monostotic fibrous dysplasia). In 3% of cases. The skull is often. affected. the three together constitute McCune-Albright syndrome.intracanalicular papilloma an arborizing nonmalignant growth within the ducts of certain glands. and any other bone(s) can be involved. particularly of the breast. affecting 70-80%. usually attached to the wall by a stalk. people suffering from fibrous dysplasia also have endocrine diseases and skin pigmentation. inverted papilloma one in which the proliferating epithelial cells invaginate into the underlying stroma. Especially when involving the skull or facial bones. the lesions can cause externally visible deformities. Presentation These lesions are tumor-like growths that consist of replacement of the medullary bone with fibrous tissue. causing the expansion and weakening of the areas of bone involved. it may be solitary.
Levels of the transcription factor C-fos are raised in fibrous dysplasia.  There are two types of fibrous dysplasia: 1.  Causes Fibrous dysplasia is very rare. leading to gene over-expression and tumour formation. Polyostotic (Involving many bones). often occurring as early as 6 years old. It is not hereditary. not much is known about it. and there is no known cure.These endocrine diseases include precocious (early) puberty. The most severe form of polystotic fibrous dysplasia is known as Albright Syndrome . Monostotic (Involving a single bone) 2.