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By: J. Curtis, M.B. B.CH., M.B.B.Ch., Ph.D.

Vice Chair, Columbia University Roy and Diana Vagelos College of Physicians and Surgeons

Slow pain is described as burning pain allergy medicine zyrtec or claritin best clarinex 5 mg, aching pain allergy symptoms and diarrhea discount clarinex 5 mg on-line, and throbbing pain and is produced when there is tissue destruction allergy induced asthma purchase discount clarinex, as for example, in the development of an abscess or in severe arthritis. Fast pain is experienced by mechanical or thermal types of stimuli, and slow pain may be elicited by mechanical, thermal, and chemical stimuli. Many chemical substances have been found in extracts from damaged tissue that will excite free nerve endings. These include serotonin; histamine; bradykinin; acids, such as lactic acid; and K ions. The threshold for pain endings can be lowered by prostaglandins and substance P, but they cannot stimulate the endings directly by themselves. The individual should be aware of the existence of stimuli that, if allowed to persist, will bring about tissue destruction; pain receptors have little or no adaptation. Functions of the Ascending Tracts 147 Conduction of Pain to the Central Nervous System Fast pain travels in peripheral nerves in large diameter A delta axons at velocities of between 6 and 30 msec. The fast pain impulses reach consciousness first to alert the individual to danger so that a suitable protective response may take place. Conduction of Pain in the Central Nervous System the afferent pain fibers enter the spinal cord, for example, in the posterior roots of a spinal nerve and terminate predominantly in the superficial layers of the posterior gray horn. The main excitatory neurotransmitter released by the A delta fibers and the C fibers is the amino acid glutamate. Whereas glutamate is a fast-acting localized neurotransmitter, substance P has a slow release and diffuses widely in the posterior horn and can influence many neurons. The initial sharp,pricking,fast-acting pain fibers stimulate the second-order neurons of the lateral spinothalamic tract. The axons immediately cross to the opposite side of the spinal cord and ascend to the thalamus where they are relayed to the sensory post central gyrus. The burning, aching, slow-acting pain fibers also stimulate the secondorder neurons of the lateral spinal thalamic tract in the posterior gray horn and ascend with the axons of the fast-acting pain fibers. It is now believed, however, that most of the incoming slow fibers to the spinal cord take part in additional relays involving several neurons in the posterior horn before ascending in the spinal cord. The repeated arrival of noxious stimuli through the C fibers in the posterior gray horn during severe injury results in an increased response of the second-order neurons. This winding up phenomenon is attributed to the release of the neurotransmitter glutamate from the C fibers. For example, if one hits the thumb with a hammer, there is no doubt where the injury has occurred. For example, in a patient with osteoarthritis of the hip joint,the individual can only vaguely localize the pain to the hip area and not to the specific site of the disease. This may be explained by the fact that fast pain fibers directly ascend the spinal cord in the lateral spinothalamic tract, whereas the slow pain fibers take part in multiple relays in the posterior gray horn before ascending to higher centers. As the result of research using the positron emission tomography scan,the postcentral gyrus,the cingulate gyrus of the limbic system, and the insular gyrus are sites concerned with the reception and interpretation of the nociceptor information. The postcentral gyrus is responsible for the interpretation of pain in relation to past experiences. The cingulate gyrus is involved with the interpretation of the emotional aspect of pain, whereas the insular gyrus is concerned with the interpretation of pain stimuli from the internal organs of the body and brings about an autonomic response. The reception of pain information by the central nervous system can be modulated first in the posterior gray horns of the spinal cord and at other sites at higher levels. Pain Control in the Central Nervous System the Gating Theory Massage and the application of liniments to painful areas in the body can relieve pain. The technique of acupuncture, which was discovered several thousand years ago in China, is also beneficial in relieving pain. Low-frequency electrical stimulation of the skin also relieves pain in certain cases. Although the precise mechanism for these phenomena is not understood, the gating theory was proposed some years ago.

Lateral to the sulcus limitans is the area vestibuli produced by the underlying vestibular nuclei allergy symptoms 1dp5dt buy clarinex canada. Groove for basilar artery Cerebral peduncle of midbrain Superficial transverse pontine fibers Motor root of trigeminal nerve Sensory root of trigeminal nerve Abducent nerve Roots of facial nerve Pons Vestibulocochlear nerve Middle cerebellar peduncle Glossopharyngeal nerve Cerebellum Roots of vagus nerve Olive Accessory nerve Pyramid Hypoglossal nerve Medulla oblongata Figure 5-17 Anterior surface of the brainstem showing the pons allergy medicine for diabetics effective 5 mg clarinex. Gross Appearance of the Pons 207 Substantia ferruginea Midbrain Trochlear nerve Median sulcus Superior cerebellar peduncle Medial eminence Sulcus limitans Vestibular area Facial colliculus Middle cerebellar peduncle Pons Striae medullares Inferior cerebellar peduncle Medulla oblongata Figure 5-18 Posterior surface of the brainstem showing the pons salicylate allergy symptoms uk purchase clarinex with amex. Cavity of fourth ventricle Medial longitudinal fasciculus Facial colliculus Vestibular nuclei Inferior cerebellar peduncle Reticular formation Middle cerebellar peduncle Spinal tract and nucleus of trigeminal nerve Superior medullary velum Superior cerebellar peduncle Nucleus of abducent nerve Motor nucleus of facial nerve Medial lemniscus Transverse pontine fibers Facial nerve Abducent nerve Trapezoid body Groove for basilar artery Bundles of corticospinal and corticonuclear fibers Pontine nuclei Figure 5-19 Transverse section through the caudal part of the pons at the level of the facial colliculus. The spinal nucleus of the trigeminal nerve and its tract lie on the anteromedial aspect of the inferior cerebellar peduncle. The trapezoid body is made up of fibers derived from the cochlear nuclei and the nuclei of the trapezoid body. The basilar part of the pons, at this level, contains small masses of nerve cells called pontine nuclei. The corticopontine fibers of the crus cerebri of the midbrain terminate in the pontine nuclei. The axons of these cells give origin to the transverse fibers of the pons, which cross the midline and intersect the corticospinal and corticonuclear tracts, breaking them up into small bundles. The transverse fibers of the pons enter the middle cerebellar peduncle and are distributed to the cerebellar hemisphere. This connection forms the main pathway linking the cerebral cortex to the cerebellum. The structure of the pons may be studied at two levels: (1) transverse section through the caudal part, passing through the facial colliculus, and (2) transverse section through the cranial part, passing through the trigeminal nuclei. See Table 5-3 for a comparison of the two levels of the pons and the major structures present at each level. Transverse Section Through the Caudal Part the medial lemniscus rotates as it passes from the medulla into the pons. It is situated in the most anterior part of the tegmentum, with its long axis running transversely. The fibers of the facial nerve wind around the nucleus of the abducent nerve, producing the facial colliculus. The fibers of the facial nerve then pass anteriorly between the facial nucleus and the superior end of the nucleus of the spinal tract of the trigeminal nerve. The medial longitudinal fasciculus is situated beneath the floor of the fourth ventricle on either side of the midline. The superior part of the lat- Transverse Section Through the Cranial Part the internal structure of the cranial part of the pons is similar to that seen at the caudal level. The motor nucleus of the trigeminal nerve is situated beneath the lateral part of the fourth ventricle within the reticular formation. The emerging motor fibers travel anteriorly through the substance of the pons and exit on its anterior surface. The principal sensory nucleus of the trigeminal nerve is situated on the lateral side of the motor nucleus. The entering sensory fibers travel through the substance of the pons and lie lateral to the motor fibers. Table 5-3 Level Comparison of the Different Levels of the Pons Showing the Major Structures at Each Levela Cavity Nuclei Motor Tracts Sensory Tracts Facial colliculus Fourth ventricle Trigeminal nuclei Fourth ventricle Facial nucleus, abducent nucleus, medial vestibular nucleus, spinal nucleus of cranial nerve V, pontine nuclei, trapezoid nuclei Main sensory and motor nucleus of cranial nerve V, pontine nuclei, trapezoid nuclei Corticospinal and corticonuclear tracts, transverse pontine fibers, medial longitudinal fasciculus Corticospinal and corticonuclear tracts, transverse pontine fibers, medial longitudinal fasciculus Spinal tract of cranial nerve V; lateral, spinal, and medial lemnisci Lateral, spinal, and medial lemnisci a Note that the reticular formation is present at all levels. Internal Structure of the Pons 209 Medial longitudinal fasciculus Reticular formation Superior medullary velum Superior cerebellar peduncle Cavity of fourth ventricle Motor nucleus of trigeminal nerve Main sensory nucleus of trigeminal nerve Pontine nuclei Middle cerebellar peduncle Sensory root of trigeminal nerve Spinal lemniscus Medial lemniscus Trapezoid body Motor root of trigeminal nerve Transverse pontine fibers Bundles of corticospinal and corticonuclear fibers Figure 5-20 nuclei. Transverse section through the pons at the level of the trigeminal Cavity of fourth ventricle Medial longitudinal fasciculus Cerebellum Superior medullary velum Superior cerebellar peduncle Main sensory nucleus of trigeminal nerve Motor nucleus of trigeminal nerve Middle cerebellar peduncle Medial lemniscus Transverse pontine fibers Bundles of corticospinal and corticonuclear fibers Pontine nuclei Figure 5-21 Photomicrograph of a transverse section of the pons at the level of the trigeminal nuclei. The superior cerebellar peduncle is situated posterolateral to the motor nucleus of the trigeminal nerve. The trapezoid body and the medial lemniscus are situated in the same position as they were in the previous section. The lateral and spinal lemnisci lie at the lateral extremity of the medial lemniscus. Its long axis inclines anteriorly as it ascends through the opening in the tentorium cerebelli.

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This correlation that greater the affinity of the corticosteroid to the receptor the more powerful its effects allergy symptoms virus order clarinex 5mg on line, bolsters the theory that corticosteroids need to bind to the glucocorticoid receptor to have physiological effects allergy zucchini symptoms order 5mg clarinex amex. The corticosteroid receptor complex causes numerous changes in the cell allergy medicine breastfeeding order 5 mg clarinex visa, both in the short term as well as long term. This theory was replicated in a study showing that dexamethasone inhibits vasculogenesis in a tumor through suppressing vascular endothelial growth factor A. Treatment of steroid along with mifepristone prevented this suppressive effect (Greenberger et al. A limit of the conclusion, however, is that both studies were done using the same corticosteroid dexamethasone, and therefore, After binding to the corticosteroid, the activated does not prove that other corticosteroids need to bind to glucocorticoid receptor complex is transported from the the glucocorticoid receptor to have an effect. In the United States, corticosteroids are dexamethasone induced promoter activity for the glucodivided in classes from one, the extremely potent, to sev- corticoid response elements and caused transcription of en, the least potent. In Europe, classes are numbered these genes beginning four hours after treatment of cells. These results indicate the influence of corticosteroids on transcription, which will subsequently affect proteins produced by the cell. Some of the genes contained within the glucocorticoid response elements code for proteins with antiinflammatory effects, such as interleukin 10. Leucine zipper protein and I kappa beta alpha (IkB) are proteins synthesized in a cell exposed to corticosteroid. They suppress an important proinflammatory transcription factor called nuclear factor kappa B (Barnes, 2006). Some genes are indirectly inhibited by corticosteroids through the suppression of nuclear factor kappa B (Maneechotesuwan et al. There are also genes directly inhibited by corticosteroids, and these genes are considered to be negative glucocorticoid response elements. Examples of these directly suppressed genes include genes that regulate osteocalcin and keratin (Barnes, 2006). The suppression of these proteins results in common side effects of corticosteroids, such as epidermal, and to a lesser extent, dermal thinning and increased risk of fractures. Corticosteroids inhibit proteins that have deleterious effects on specific pathologies. A study seeking to explain the function of corticosteroid therapy in the treatment of infantile hemangioma found that the medicinal property was due to a negative glucocorticoid response elements and a decrease in amount of a corresponding protein. This effect was replicated using different corticosteroids including dexamethasone, prednisone, prednisolone, methylprednisolone, and hydrocortisone (Greenberger et al. Other proangiogenic factors were suppressed in the hemangioma stem cells, in addition to vascular endothelial growth factor A. These factors included matrix met40 alloproteinase 1, interleukin-6, and monocyte chemoattractant protein 1. The latter two molecules are both involved with the immune system (Greenberger et al. Inhibition of metalloproteinase is also seen in corticosteroid treatment of arthritic diseases (Fubini et al. The expressed genes, as well as the repressed genes, have physiological effects on the cell, which are attributed to the corticosteroid. Numerous studies demonstrate that corticosteroids affect transcription, but this does not explain all of the physiological effects of corticosteroids. Corticosteroids inhibit cytokine production in T helper 2 cells, specifically interleukin 4, 5, and 13. The genes coding these interleukins are not fully regulated by nuclear factor kappa B and are not known to be part of the glucocorticoid response element (Maneechotesuwan et al. Additionally, effects of dexamethasone were seen in cells after only ten minutes, quite a short time for the transcription of glucocorticoid response element genes and translation of corresponding proteins. Furthermore, although the inhibitor of transcription actinomycin D blocked the promoter of the glucocorticoid response elements, overall the molecule did not inhibit the physiological changes of a cell exposed to dexamethasone (Hafezi-Moghdam et al. Based on these observations, the theory that corticosteroids binding to a receptor cause a cell to express certain genes and repress others is insufficient. Treating endothelial cells with dexamethasone stimulated endothelial nitric oxide synthase, an enzyme that has physiological effects on the cells. Activating the enzyme begins with the corticosteroid binding to the glucocorticoid receptor.

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The band of anesthesia and analgesia was caused by the destruction of the cord on the left side at the level of the 10th thoracic segment; all afferent nerve fibers entering the cord at that point were interrupted allergy symptoms pressure in head best 5mg clarinex. The loss of pain and thermal sensibilities and the loss of light touch below the level of the umbilicus on the right side were caused by the interruption of the lateral and anterior spinothalamic tracts on the left side of the cord allergy shots grass buy 5 mg clarinex overnight delivery. To comprehend what has happened to this patient allergy testing elizabethtown ky purchase clarinex 5 mg otc,a knowledge of the relationship between the spinal cord and its surrounding vertebral column must be understood. The various neurologic deficits will become easier to understand after the reader has learned how the nervous pathways pass up and down the spinal cord. The nervous system is composed basically of specialized cells, whose function is to receive sensory stimuli and to transmit them to effector organs,whether muscular or glandular. The sensory stimuli that arise either outside or inside the body are correlated within the nervous system, and the efferent impulses are coordinated so that the effector organs work harmoniously together for the well-being of the individual. In addition, the nervous system of higher species has the ability to store sensory information received during past experiences. This information,when appropriate,is integrated with other nervous impulses and channeled into the common efferent pathway. Autonomic Nervous System the autonomic nervous system is the part of the nervous system concerned with the innervation of involuntary structures, such as the heart, smooth muscle, and glands within the body. The autonomic system may be divided into two parts, the sympathetic and the parasympathetic, and in both parts, there are afferent and efferent nerve fibers. The activities of the sympathetic part of the autonomic system prepare the body for an emergency. The activities of the parasympathetic part of the autonomic system are aimed at conserving and restoring energy. In the central nervous system, the brain and spinal cord are the main centers where correlation and integration of nervous information occur. Both the brain and spinal cord are covered with a system of membranes,called meninges, and are suspended in the cerebrospinal fluid; they are further protected by the bones of the skull and the vertebral column. The central nervous system is composed of large numbers of excitable nerve cells and their processes,called neurons, which are supported by specialized tissue called neuroglia. The interior of the central nervous system is organized into gray and white matter. White matter consists of nerve fibers embedded in neuroglia; it has a white color due to the presence of lipid material in the myelin sheaths of many of the nerve fibers. In the peripheral nervous system,the cranial and spinal nerves, which consist of bundles of nerve fibers or axons, conduct information to and from the central nervous system. Spinal Cord the spinal cord is situated within the vertebral canal of the vertebral column and is surrounded by three meninges. Further protection is provided by the cerebrospinal fluid, which surrounds the spinal cord in the subarachnoid space. Below, the spinal cord tapers off into the conus medullaris, from the apex of which a prolongation of the pia mater, the filum terminale, descends to attach to the back of the coccyx. Along the entire length of the spinal cord are attached 31 pairs of spinal nerves by the anterior or motor roots and the posterior or sensory roots. Each root is attached to the cord by a series of rootlets, which Major Divisions of the Central Nervous System 3? Memory Sensory stimuli Afferent Correlation coordination Efferent Muscles, glands, etc. Figure 1-1 the relationship of afferent sensory stimuli to memory bank, correlation and coordinating centers, and common efferent pathway. Cerebrum Forebrain Brachial plexus Midbrain Pons Hindbrain Medulla oblongata Cerebellum Phrenic nerve Radial nerve Lumbar plexus Median nerve Cervical Ulnar nerve Sacral plexus Obturator nerve Sciatic nerve Spinal cord Thoracic Femoral nerve Lumbar Sacral Coccygeal A B Figure 1-2 A: the main divisions of the central nervous system. B: the parts of the peripheral nervous system (the cranial nerves have been omitted). These are, in ascending order from the spinal cord, the hindbrain, the midbrain, and the forebrain. The hindbrain may be subdivided into the medulla oblongata, the pons, and the cerebellum. The forebrain may also be subdivided into the diencephalon (between brain), which is the central part of the forebrain, and the cerebrum. The brainstem (a collective term for the medulla oblongata, pons, and midbrain) is that part of the brain that remains after the cerebral hemispheres and cerebellum are removed.

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