Neurological Aspects of Pain

Neurological Aspects of Pain 1.1. Functional Properties of Nerve Fibres 1.1.1. Properties of Peripheral Somatic Nerves Peripheral somatic nerves consists generally of somatic-motor, autonomic-motor and sensible fibres. 1.1.1.1. Somatic-motor fibres for the striated musculature The cell bodys of somatomotor fibres for the striated musculature are always lying in the brainstem (12 pare cerebral nerves) or the fore horn of the whole spinal medulla. The stimulus runs from central to peripheral (efferent). The lateral cutaneous femoral nerve consists of sensible fibres and no motor fibres. The shiatic nerve consists of 20% motor fibres, 30% sensible, and 50% sympathetic fibres. The gluteal nerves consist of pure motor fibres, sympathetic fibres and no sensible fibres. 1,2 1.1.1.2. Autonomic-motor fibres for the smooth muscles of blood- and lymphatic vessels The autonomic-motor fibres for the smooth muscles of the blood and lymphatic vessels are of sympathetic origin. Venes are not innervated. They function by the musculare pump system and in some cases by valves. The cells bodies of the autonomic-motor fibres are situated in the lateral horn between C8-L2. They are termed: the centro-ganglionar neurons. All motor neurons, situated in the spinal medulla go via the fore horn to the peripheral nerve. It must be mentioned that all smooth muscles can contract without external innervation (for example: heart, gut). This is due to the intrinsic nerve system with is influenced by the sympathetic and parasympathetic nervous system. 3-5 1.1.1.3. Sensible fibres for somatic structures The sensible fibres for somatic structures originate from muscles, tendons, capsules, joints, ligaments and bones. Their cell bodies are lying in the spinal ganglions of the corresponding nerve (= afferent). 2,6 1.1.1.4. Sensible fibres for autonomic structures: blood- en lymphatic vessels The cell bodies of the sensible fibres for autonomic structures are situated in the spinal ganglions of the segments where the sympathetic neurons start (SI-joint: T11-L1). The peripheral autonomic nerve contains generally autonomic-motor and sensible fibres and serves for the innervation of organs. Glands are always dubble innervated (sympathetic and parasympathetic), except for the adrenals. 2 Examples: The femoral arterie contains sensible fibres which go to the spinal ganglions and arrive in the dorsal horn where connections exist, via intercalar neurons, with the origins of the sympathethic fibres of the levels T10-T11. Knee joint: is sensible innervated via the sciatic nerve (posterior side of the knee), but in the knee capsule, sensible fibres exist which connect via the femoral arterie the levels T10-T12. 1.1.2. Properties of Peripheral Autonomic Fibres Peripheral autonomic nerves consist of autonomic-motor and sensible fibres. They innervate organs and glands. 1.1.2.1. Viscero-sensible fibres The cell bodies of viscero-sensible nerve fibres are situated in the spinal ganglions of those segments from where the sympathetic and parasympathetic neurons start. Example: the pelvis organs: S2-S4 and/or TLJ (= thoracolumbar junction). The TLJ receives a lot of information. Some of those stimuli go via the nervous supply in the blood vessel wall. 2 1.1.2.2. Motor fibres for smooth muscles The parasympathetic primary cells are situated in the brain stem to the level of C2 and the lateral horn of S2-S4. The sympathetic origin is situated in the lateral horn of C8-L2. 2,7,8 1.1.3. Axoplasma Flow of the Axons Materials and substances are moved within the cytoplasm of all cells. In the axoplasm (= cytoplasm of neurons), structures such as the smooth endoplasmic reticulum, ribosomes, microtubules and neurofilaments likely take part of the axoplasmic transport mechanism. Perhaps the human movement plays a role in this intracellular motility 9. In the cytoplasm of nerve fibres nutrients and transmitters are moved. At the nerve ends vesicles are located, that continue the transport into the gap junction. The transport in the axoplasma is termed antidrome and orthodrome transport. Antidrome (antegrade) transport occurs from central to the periphery and orthodrome (retrograde) transport in the opposite direction.1,10,11 For the sciatic nerve the antidrome transport is rather fast (12 hours), the orthodrome transport is slower (48 hours). 1.1.3.1. Signal transfer of the peripheral nerve fibres Ion-channels and receptors play an important role in the signal transfer of the peripheral nerve fibres. The ion-channels are located on the extremities of the fibres. They make the transport for the neurotransmitters possible. Receptors are specified. Every cell has ÂÂ ± 1 million receptors. The gates of the ion-channels (mostly proteins) can be inhibitory or excitatory. The Swann-cells are spread over the axon and form de myelin sheet. The myelin sheets are interrupted by the knots of Ranvier. In the CNS they are termed glial cells. The glial cells have several functions. The myelin sheets have a certain thickness. Unmyelinated axons have Schwann-cells as well. In myelinated axons the stimulus progresses salutatory and in unmyelinated axons the stimulus progresses slowly. The signal transfer of the peripheral nerve fibres has 3 kinds of stimulus progress being chemical transport, electric stimuli progression and axoplasm flow. Chemical transport occurs at the nerve ends, and consists of neurotransmitters. The transport depends of the kind of ion-channel, the neurotransmitter and the receptor. Electric stimuli progress over the axon and occur by opening of the ion-channels stimulation the own nerve ends due to production of the neurotransmitters. The speed of transmission depends of the presence of a myelin sheet and the diameter of the fibres. The axoplasm flow of the neurotransmitter in axoplasma (= chemical) occurs in 2 directions. Sometimes the pain can occur 24 hours after injury! It can also be very slow (up to 48 hours) and be resposible for the delayed onset of pain. 1,11 1.1.3.2. Morphologic and functional classification of nerve fibres: Understanding pain phenomen the morphologic and functional properties of nerve fibres is important. In time several classification systems have been investigated and proposed. 1.1.3.3. Classifying axons according to their conduction velocity In the 1920s and 1930s, there was a virtual use of classifying axons according to their conduction velocity 13. Three main categories were discerned, called A, B and C fibres: C fibres are the smallest and slowest. Mechanoreceptors generally fall in category A. The A group is further broken down into subgroups designated: the a fibres: the fastest the b fibres the d fibres: the slowest The muscle afferents axons are usually classified into four additional groups: I: the fastest II, III and IV: the slowest, with subgroups designated by lower case roman letters. 1.1.3.4. Properties of the A-d, A-b sensors or type I en II fibres The A-a and A-b fibres have low threshold properties. They are low threshold afferents/efferents, they have a quick adaptation, are bi- or monosynaptic and unimodal (= mechanosensors: only sensible for mechanical stimuli). They cross the midline in the spinal medulla. The A-b provides information about normal pressure or strain tension and the A-a provides information about position changes of joints in space. They give information about the smooth touch and kinesaesthesis in the skin. 1.1.3.5. Properties of the A-d and C sensors or type III en IV fibres 1.1.3.5.1. The A-d sensors or type III fibres The A-d or type III fibres are selective and have a slightly higher threshold than the A-a and the A-b sensors. They have a longer adaptation time. After a pin prick the pain keeps going on for a time which is a specific property of the A-d sensors. They are multisynaptic and cross the midline in the spinal medulla. A-d sensors are polymodal. They provide information about mechanical stretch and pressure forces from normal to noxious. They give information about temperature from normal to noxious stimuli. From 36,5ÂÂ °C tot 42ÂÂ °C especially C-fibres are involved. From 36,5ÂÂ °C tot 38ÂÂ °C the A-d fibres are responsible. A quantity of those fibres is noxious. They are termed: nocisensors but not all. Some measure only normal temperatures and they become nocisensors in case of tissue injury. 11 1.1.3.5.2. The C sensors or type IV fibres The C or type IV fibres are selective and have a high till very high threshold. They are slow to very slow with a long adaptation time. They have tonic and continuous activity properties. They cross the midline in the medulla medulla and are polymodal. The C fibres measure the chemical consistence of tissues from normal to noxious. They measure temperature from normal till abnormal (= noxious). Some of those fibres are nocisensors but not all of them. Example: the sensibility of the knee consists of 80% normal sensibility sensors and 20% nocisensors. 11 1.1.3.5.3. Difference between nocisensor- stimulation and pain A nocisensor measures the damage of injured tissue. A nocisensor can but must not necessarily provoke pain. A part of the A-d and C-fibres are nocisensors. They measure the damage or the almost-damage (mechanic, temperature, chemical). Their noxious stimulation does not always lead to pain perception. Here fore the stimulus must attain the thalamus and cerebral cortex, otherwise there is no pain sensation. Not all nociceptory stimuli rise so high to the midbrain or cortex. A lot of stimuli extinguish in the spinal medulla, the ascending pathways or in the brainstem. The stimulus attains the pain centres when the intensity of one stimulus is sufficient or when summation occurs of several stimuli in parts of the dorsal horn. As well reflectory (unconscious) as cognitive (conscious) reactions occur and the nocisensors will provoke pain, in case of severe damage. Thus, not all nocisensors provoke pain but they can be considered as normal pain fibres. It is logic that if a nocisensor is s ufficiently stimulated it will provoke the sensation of pain. A-d en C fibres can give pain thats not only caused by the damage itself, but as a result of the damage as well. A pain feelin which is more intense than normally expected is termed hyperalgesia. For example, when ice is applied on the skin it hurts but ice applied on a burned skin does hurt even more. When punctuated stimuli are applied on the course of the sciatic nerve it normally hurts but in case of sciatica it hurts even more (= hyperalgesia). Hyperalgesia is hypersensitivity on a stimulus that normally hurts, due to over stimulation of the nocisensors. The A-a and A-b fibres normally do not give pain, because they are not nocisensors. They register only normal values. Under certain circumstances they provoke pain. This happens in case of injured tissues or nerves or when the nocisensors become active. When nocisensors already give pain as a result of a decreased threshold, then the A-a and A-b fibres become sensiti ve as well. A light pressure on the pain area will also be painful. A low pressure- or strain force on the skin, tendons or muscles normally provoke no pain, but in case of damage it will well provoke pain. This is termed allodynia. Allodynia is pain that is caused by a stimulus that normally doesnt hurt due to an increased sensitivity of the the A-a and A-b fibres. This phenomon gives an opportunity to test the pain perception of the nervous system by use of pricking or brushing tests on the painfull area. There is a difference between nocisensor stimulation and the pain interpretation. 11 Table 5: Difference between nocicensor stimulation and pain. By use of selective stimulation the A-a and A-b fibres can be stimulated without that the A-d and C-fibres become active. This is caused by the low threshold of the A-a and A-ÃÆ'Ã… ¸ fibres compared with the A-d and C-fibres. A-d en C-fibres cant be stimulated selectively by use of mechanical stimuli because at the moment those fibres are stimulated; already the A-a and A-ÃÆ'Ã… ¸ fibres are active. When those become active, all fibres were stimulated. Also in case of nociception all those fibres are active. Selective stimulation can be used during TENS application or during active en passive mobilisations applied under the pain threshold level. 11 1.1.4. Hierarchy of the Nervous System The information processing in the nervous system happens on 4 levels. As well as the peripheral nerve ends, the dorsal horn, the brainstem and sub cortical and cortical levels are involvend. 1,7,11 1.1.4.1. The peripheral nerve ends The peripheral nerve ends are responsible for the uptake of information. The receptors are modulated by the state of surrounding tissue and the condition of the peripheral nerve. 1.1.4.2. The dorsal horn of the spinal medulla The dorsal horn modulates the incoming signals and is influenced by the state of the dorsal horn and the quantity and kind of gathered stimuli. 1.1.4.3. The brainstem The brainstem provides the primary responses with autonomic and hormonal modulations as a response to stimulation. 1.1.4.4. Sub cortical and cortical levels The sub cortical and cortical area provides the conscious cognitive and psycho-emotional modulation. The processing of the information and response on stimulation depends on the hierarchic manner, but always occurs with a total integration of the whole nerve system. 1.1.4.5. The Archi-, Paleo- and Neo level of the nervous system The nervous system can be ordered depending on a hierarchic manner in an archi, paleo and a neo level. 7 1.1.4.5.1. The Archi level The archi level consists of the gray matter (dorsal horn) of the spinal medulla, the ascending multisynaptic pathways in and around the gray matter, the medial pathways of the anterolateral quadrant, the mid part of the cerebellum and the brainstem (reticular formation). It is responsible for the most automatic movements after Hughlings Jackson. 7 1.1.4.5.2. The Paleo level The paleo level consists of the ascending pathways of the anterolateral quadrant, the descending pathways in the ventro-lateral quadrant, the hormonal and vestibular nuclei in the brainstem, the hypothalamus, certain parts of the cerebellum and the limbic system. Humoral influences from the liquor can influence (endofins) the sensibility of the pain system. 7 1.1.4.5.3. The Neo level The neo level consists of the dorsal ascending pathways, the dorso-lateral and ventral descending pathways, the cerebellar cortex, the lateral thamalus nuclei and the cerebral cortex. It is responsible for the cognitive mental processes, accurate skills and least automatic functions. 7 1.1.4.6. Phylogenetic development of the nervous system The phylogenetic development of the nervous system differs in time for the different levels. The archi-system is the oldest and is identical to that of the lower vertebrates. It is completely developed when born. The paleo-system is younger than the archi-system. It is identical of that of the lower vertebrates but only half developed when born. The neo-system is het youngest system in the phylogenetic evolution. It is much more developed than that of the lower vertebrates and not developed when born. 7 1.1.4.7. Functional properties of the different hierarchic systems of the nervous system Specific properties can be indicated to the different hierarchic levels of the nervous system. 1.1.4.7.1. Functional properties of the Archi level The archi level consists of C and A-d fibres. It is a relatively slow and tonic (continuous) working system that stands for the basic needs of life e.g.: basic survival or most automatic movements and autonomic functions such as basic tonus regulation in the brainstem and medial cerebellum. It is responsible for primary pain modulation e.g.: redraw reflex and increased tonus. 1.1.4.7.2. Functional properties of the Paleo level The paleo level consists especially of A-d, A-b, and C-fibres as well. It is a relative quicker system but also has tonic activity properties. The paleo level supports the archi-level by use of hormonal adaptation and psycho-emotional adaptation. It takes part of the autonomic function (hormonal function), fight/flight reactions in case of stress and pain and posture regulation (static posture balance). 1.1.4.7.3. Functional properties of the Neo level The neo level consists especially of A-a and A-b fibres and is very quick with phasic responses on stimulation. It analyses the information of the archi- and paleosystem and is guided by use of cognitive responses. The least automatic movements are guided and conscious movements. It regulates the dynamic posture balance and automatisation of movements. It is responsible for the organ sense perception and dissociated movement. 1.1.4.7.4. Interaction and control of the different hierarchic systems in the nervous system General principles of interaction among the different hierarchic systems in the nervous system can be summarized as follows. The paleo-system controls the archi-system and guides it. The neo-level controls the archi- and paleo system and guides both. The neo-level surrounds literally the archi and paleo level. The grey matter is situated medially in the nervous system medial in spinal medulla, the white matter laterally. The neo-system keeps the paleo-level and archi-level in harness. The hierarchic construction of the nervous system can be seen as a gate control system that exists on all levels. 7 1.1.4.7.5. Gate-control in the peripheral nerve fibres Axo-axonal connections between lower and higher fibres exist. The A-a and A-b fibres give off collaterals in the dorsal horn. The A-a and A-b attain the spinal medulla faster and prepare it for the arrival of A-d and C-stimuli. Selective stimulation of higher fibres (A-a and A-b fibres) inhibits the working of the fibres of lower order (A-d and C-fibres). 1.1.4.7.6. Gate control in the dorsal horn At the level of the dorsal horn interaction and control mechanisms exist and this phenomen known as Gate-control in the dorsal horn is also known as the gate theory of Melzack en Wall. The outlets of the A-a en A-b neurons shunt on the outlets of the A-d and C-neurons and their neurotransmitters close the ion-channels of these. The descending pathways of the paleo- and neosystem do the same and work on the interneurons and inhibit the A-d and C-neurons. 11 1.1.4.7.7. Gate-control in the brain The cortical pathways control the sub cortical pathways. They inhibit the brainstem reflexes. Conscious movements and intentions inhibit unconscious tonic reflexes (Example: relaxation). The cortical and sub cortical pathways regulate a directed and conscious life. The brainstem provides the autonomic support. This is all controlled by neurotransmitters. The perception of nociceptive pain not only involves the sensation transmitted and regulated by peripheral and central neurons, but is also affected by higher brain functions. 11 1.1.4.7.8. The uptake of nociception information A-d and C-fibres are the only fibres that can registrate nociception. The A-d fibres are quicker and give epicritic pain when the stimulus is attaining the pain centres. Epicritic pain means precise localisation with immediate redraw reflexes. The kind of pain is described as stabbing, boring, tearing or pulling. The impulses of the C-fibres attain the pain centres much later. They give protopathic pain, which is a continuous pain. That pain is not precisely located. Protopathic pain is burning, booring of a kind and continues much longer. It goes together with autonomic reactions, for expample: oedema. 11 1.1.5. The dorsal horn of the spinal medulla 1.1.5.1. General survey of the classification of the grey matter of the spinal medulla The grey matter is divided in the 10 layers of Rexed. This system is named by Rexed who discovered that the neurons in the dorsal horn where organised in layers depending on their function. Every layer is present in different segments and forms rostro-caudal nuclear columns. The counting happens from the dorsal horn to the anterior horn. Every layer is in contact with another by interneurons and dendrites. Layer I and II: nocisensory outlets of both: musculo-skeletal and visceral structures Layer III: intersegmental ascending pathways (dorsal proprium tract) and outlets to the spinothalamic tract (anterolateral quadrant) Layer IV: exclusive nocisensors from the musculoskeletal system Layer V-VI: fibres arriving from the nocisensors of the skin and viscera Layer VII: lateral horn: interneurons and sympathetic neurons Layer VIII en IX: motoneurons for musculoskeletal system Layer X: hormonal neurons In all levels descending pathways arrive from diverse levels of the brain. 1.1.5.2. Somatotopic ordering of nocisensors in the dorsal horn In layer I-II the nocisensors of viscera and musculo-skeletal structures are laying next to each other. They are ordered in a sagittal way from medial to lateral. The medial structures project medial and lateral structures project laterally. In layer V the nocisensors of certain skin areas are lying next to the nocisensors of viscera. Those are ordered in horizontal layers. For example: the organ-nocisensors under the level of the diafragm are lying next to the skin sensors from Th7-Th10. 1.1.5.3. Segmental interactions in the dorsal horn Normal reactions in musculo-skeletal influence the nocisensoric function. Outlets of nocisensors stimulate interneurons. There exists interaction with the spinothalamic tract and interaction with motoric anterior horn cells (somato-somatic relation). Normal reactions in musculo-skeletal nocisensoric function and influence the outlets of nocisensors stimulate the interneurons causing interaction with spinothalamic tract and with the sympathetic lateral horn cells (viscero-visceral relation). 11 Abnormal reactions can occur when the outlets of nocisensors infect the other nocisensors. Those react in turn causing interaction between motoric and visceral responses. This results in a somato-visceral relation, a somato-sympathetic relation and a viscero-somatic relation. 1.1.5.4. The Importance of Wide Dynamic Range Neurons In layer III, wide dynamic range neurons (WDR-neurons) exist. 21 Those WDR-neurons are interneurons that connect all the A-d en C-fibres from the dorsal horn. They project on the spinothalamic tract (antero-lateral quadrant). The ventral pathways go to the reticular formation, medial thalamus and the medial limbic system. The lateral pathways go to the lateral thalamus and cortex. They connect all visceral and motoric stimuli (= summation) with as consequences that motoric and visceral stimuli are sent together to the brain. The brain receives segmental information and no individual information. The brain can project pain to segmental connected structures. This is termed referred pain. Examples are: the stomach ulcer can provoke inter scapular pain or cardiac complaints and can give ulnaris nerve pain. Pain does not always indicate the exact location and origine. Anamnesis, assessment and clinical reasoning are very important. 1.1.5.5. Inhibition and excitation of the dorsal horn Inhibition and excitation of impulses in the dorsal horn can be caused by outlets of peripheral nerves. For example the A-a and A-b can inhibit the A-d and C fibres (pre-synaptic inhibiton). The outlets of the descending pathways can influence the the nerve ends and the interneurons (postsynaptic inhibition/excitation). The interneurons themselves can cause pre- or postsynaptic inhibition/excitation. Summation of stimuli defines the state of the dorsal horn. If a segment is excited or inhibited depends on the som of stimuli. Nocisensory impulses of the peripheral nerves always excite the dorsal horn. Summation of exciting nocisensoric impulses is defined by spatial and temporal facilitation. Temporal facilitation means the timing; spatial facilitation, the diverse structures that are involved. Impulses of A-a and A-b neurons act generally inhibiting. The impulses from the descending pathways can act in both ways. They are also regulated by temporal and spatial factors. The sum of sti mulating and inhibiting stimuli defines the state of the dorsal horn. An excitated dorsal horn provokes a lot of irradiating pain. 1.2. Assessment of Primary and Secondary Hyperalgesia 1.2.1. Definition of primary hyperalgesia Changes in the local sensibility of the afferent neurons as a result of a lesion in the peripheral tissues are termed hyperalgesia. In case of an increased sensibility of the A-a and A-b fibres the primary hyperalgesia is termed allodynia. In case of an increased sensibility of the A-d and C fibres the primary hyperalgesia is termed hyperalgesia. The lesion in the peripheral tissue can be of inflammation or neurogenic origin. 22 1.2.1.1. Pathophysiology of primary hyperalgesia In case of tissue injury bradykinin and ATP is produced at the site of lesion. Those mediators stimulate the blood- and lymphatic vessels, the mast cells and nociceptors. In the circulation inflammatory mediators are released aswell as histamine, serotonin, NGF, leucocytes, trombocytes and others. C-fibres released neuropeptides such as SP and CGRP. Those modulate and stimulate the release of other inflammatory mediators aswell. All those mediators are termed the inflammatory soup. Those mediators also stimulate the C-fibres which causes a vicious circle. The sympathetic nerve terminals are stimulated by inflammation and release noradrenalin which also stimulates the C-fibres. The sympathetic coupling between C-fibres and sympathetic end neurons occurs. The presence of inflammatory mediators decreases the threshold of all types of endneurons with as a result local allodynia and hyperalgesia. The allodynia and hyperalgesia can spread in the surrounding tissue, by stimulating the surro unding neurons. This is termed the flair zone. 22,23 Figure 16: Consequences of tissue injury: the inflammatory soup. 14 1.2.1.2. Primary hyperalgesia and the dorsal horn The A-d mechanoreceptors and nociceptors, and C-nocisensors stimulate the dorsal horn of somatic connected segments. As a consequence a temporary wind-up can occur. A wind-up is an over stimulation that can hold on for 72 hours. A refectory muscular reaction occurs around the lesion aswell. As a result the stimulation via the ascending pathways (antero-lateral quadrant) to the brain increases. Protopatic pain (quick, stabbing pain) followed by epicritical pain (boring, continuous pain) occurs. The brainstem regulates the autonomic reactions further such as sympathetic, hormonal, and emotional. The C-nocisensors give stimuli to the sympathetic connected segments. As a result the sympathetic system stimulates the C-endneurons (= sympathetic coupling) and vasoconstriction on the arterioles and lymphatic vessels. 20,24 1.2.1.3. Primary hyperalgesia and nerve injury When compressed inflammation occurs as prescribed above. In case of long standing injury, an ectopic injury occurs. This can be located on different locations on the peripheral nerve with the result that hyperalgesia and allodynia occurs on the course of the nerve, the connected dermatomes and this from the nerve root! In the spinal ganglion of the nerve, the sympathetic endneurons grow round the nerve cells with the occurrence of basket formations as a result. Consequently sympathetic maintained pain (SMP) occurs, also termed causalgia. This phenomon can continue for 7 to 10 weeks after the lesion but can also continue afterwards. 10 25 To summarize we can state that inflammation provokes a local hyperalgesia and allodynia, which spreads over the flair zone. Locally a vicious circle between the inflammatory soup and C-fibres takes place and sympathetic coupling between sympathetic end-neurons and C-fibres occurs. This continues until the tissue heals. Normally the medulla reacts with a temporary wind-up and a normal stimulus-response reaction. In case of neurogenic injury, causalgia may occur and sensitisation of the dorsal horn is possible. 22 1.2.1.4. Clinical pain assessment in case of primary hyperalgesia During the pain assessment, in case of primary hyperalgesia, when brushing or by use of punctuate stimuli the following properties are local allodynia and hyperalgesia restricted to the flair zone. In case of a nerve injury the flair zone is restricted to the course of the nerve root. Local sympathetic reactions occur when inflamed but are restricted in time. In case of allodynia and hyperalgesia when brushing and applying punctuated stimuli on the course of the nerve or a part of it, sympathetic reactions in the dermatome of the nerve can occure aswell. 22 1.2.2. Definition of Secondary Hyperalgesia An increased sensibility of all types of nerve fibres that continues outside the flair zone of the original lesion, linked to the course of the hyperalgesia and allodynia around the tissue, is termed secondary hyperalgesia. 22 1.2.2.1. Pathophysiology of secondary hyperalgesia When tissue is injured, nociceptors stimulate the interneurons by use of neurotransmitters such as SP, CGRP, NO, Ca, etc. The A-a and A-b neurons provide inhibiting neurotransmitters and the descending pathways give exciting or inhibiting mediators. The WDR-neurons receive al those impulses and send them to the spino-thalamic tract. WDR-neuron receptors differ. Some open ion-channels using inhibiting neurotransmitters, others open ion-channels using exciting neurotransmitters depending on the kind of receptor. If the stimulus acts inhibiting or exciting depends on the quantity of the opened inhibiting- or exciting ion-channels. In case of secondary hyperalgesia, more excitatory stimuli exist and insufficient inhibiting ways are activated. The WDR-neurons will work exiciting as well because of the fact they do not only activate the spino-thalamic pathways but also on the incoming stimulating neurons. As a result a vicious circle occurs in the dorsal horn. This provokes a decreased thr eshold of the present neurons. The sensors are also stimulated by the dorsal horn and not only by the local lesion. They become sensitized over their whole course with the consequence that the central hyperalgesia is linked to the lesion. When the local lesion is healing, the central allodynia will also disappear. Hyperalgesia is not as much linked to the course of the lesion but can last longer. Its origin is mostly caused by temporal and spatial summation of exciting stimuli. 22 1.2.2.2. Clinical pain assessment in case of secondary hyperalgesia During the pain assessment, when touching (brushing) and applying punctuate stimuli local hyperalgesia en allodynia and extending hyperalgesia and allodynia can be observed. When the pain occurs outsite the spinal column area the touching (brushing) and applied punctuate stimuli starting from the lesion and over the dermatome near by. The application must be enlarged to the neighbouring dermatomes and also to the corresponding segments of the spine. Always compare with the opposite side. Differentiate allodynia and hyperalgesia. 22 In case of primary hyperalgia the allodynia and/or hyperalgesia is restricted to the lesion area and flair zone. The allodynia disappears before the hyperalges

Influence Change through Strategic Thinking Essay

Strategic Thinking can be defined as the learning process which entails many aspects of turning the innovative ideas into reality through team work, planning and organizing of resources. It includes the need to have problem solving abilities and critical analysis of situations. Strategic thinking can be used as a very effective tool to implement; manage and sustain the change in any organization and help organizations prosper under the scheme of change (Sanders, 1998). Why is Strategic thinking necessary? Strategic thinking when compared with strategic planning serves us with many differences. With an aerial view, both of ideas seem to be very similar, however, in actual organizational based scenarios, strategic thinking is quiet different from planning, and involves more rigorous activities. Strategic thinking only helps in shaping the future that is partial planning of the future. In the process, the ideas are not discreet and are interactive in nature. This helps to generate better outputs as the interaction gives other the chances to present their opinions. Strategic thinking provides lower level management to have their say in strategy making and development as it an interactive system of thinking. The involvement of the management at all levels is what gives it an edge over strategic planning. An organization is a system in which sub systems are present. These sub systems interact with each others and hence managers at all the levels come together to create a strategy viable for their organization. All the managers understand their positions and their roles in the organization know that they are correlated and are interdependent (Wootton & Horne, 2002). Strategic thinking has one important aspect i. e. , change. Change is inevitable when strategic thinking is in process. It is true that strategic thinking tackles the difficult part of implementing the change rather than sustaining and evaluating it. Change management is difficult and the toughest part of change management is implementing and managing change (Wootton & Horne, 2002). Strategic Thinking and Influencing Change However, strategic thinking assists in successful change implementation. Change management and transformation from one state to the other is involved with rigorous planning and with out planning, change management process would come out to be a failure. Hence, strategic thinks aids in making correct decisions as it an interactive system of thinking (Kotter, 1996). The important thing is to identify whether the change is at strategic, operational or functional level, and when change is identify, it must be made sure that in order to bring about the change a paradigm shift must come. The change that would come would bring a transformation current system and the way things are done in an organization. Innovative thinking and thinking that is out of the box clearly assists in planning and implementing a strategic change in an organization. Continuous improvements and evaluation is another critical success factor in implementing change with the aid of critical thinking. In order to bring about the change effectively, the mangers must challenge the current situation they are in. complacency should be avoided at all levels of change. All assumption must be confronted and must be checked against the current scenarios if they are applicable. All the assumptions must be checked against the evidences and must be characterized and prioritized (Kotter, 1996). The managers must make a clear distinction between their ends and the means they would achieve those ends. The ends must be clearly identified and the means and methods of achieving those ends must be done when ends are assessed and are understood. Change brings about resistance, and at this stage, managers must identify the means to handle the resistance and the consequences of the resistance (Kotter, 1996). All levels of the planning process must be utilized in strategic thinking when establishing change in any organization or at stage of organizational life. These levels are mega level, macro level and micro level. At all levels of organizational change and planning process a holistic approach should be employed and used. This would help the managers understand what change would consequently which part of the system and sub system. Interaction amongst those systems would clear away the hurdles that could come in the process of change, and better ideas come up to eradicate and overcome those barriers. Relationships should be established in strategic thinking to understand that the organization is not a stand alone entity but is well connected with the outside world (Sanders, 1998). Measurable objectives must be set so that they are evaluated at a later stage of change and when the change is needed to be sustained, the specific changes can be managed well if there is a slight disorder in them. Indistinguishable and ambiguous objectives should not be adhered to and should not be taken into account. Status quo must not be challenged but a change should be with in the status quo and achievable at all levels of the organization. The pros and cons must be measured. If the success of that particular change is made measurable then the failure and damages of that particular change should also be made measurable (Kotter, 1996). Ideal vision, even though difficult to achieve, always provides the possibilities that can be present to lead to that particular ideal vision. This is the basis of strategic thinking. Continuous improvement and incessant change is the key to organization’s success. Both amalgamated give a perfect strategy to come about a successful change action with minimized resistance and better results (Sanders, 1998).

Managing and Reducing Cardiovascular Risk in Type 2 Diabetes Mellitus Essay

Diabetes mellitus is a metabolic disorder in which the body’s capacity to make use of glucose, fat and protein is disturbed due to insulin deficiency or insulin resistance. It is a hormone secreted from pancreas that helps glucose from food to enter the body’s cells where it is transformed into energy required by muscles and tissues to function. Diabetes is caused either because the pancreas does not secrete adequate insulin, or because cells do not react to the insulin that is produced. Due to this reason, an individual with diabetes does not take up glucose appropriately and glucose continues circulating in the blood (hyperglycaemia) harming tissues over time. This damage leads to acute health complications. The classic symptoms of diabetes mellitus are, Polyuria ,Polydipsia ,Polyphagia ,lethargy and weight loss. There are many causes for high blood glucose levels in the body and so a number of types of diabetes exist. Diabetes mellitus occur throughout the world. Based on the study conducted by IDF, the number of diabetics on earth stands at 365 million nearly 8. 5% of the global population. It is more widespread in the more developed countries. The greatest raise in incidence is, however, expected to happen in Africa and Asia, where majority of the diabetes patients will most likely be found by 2030. Diabetes mellitus is categorised into four broad groups: Type 1, Type 2, Gestational diabetes & â€Å"other specific types†. Scientists in US have found a Type 3 diabetes, it is still continuing further study. Type 1 diabetes is absolute insulin deficiency usually affects children and young adults. Type 2 Diabetes is an insidious progressive disease that is often diagnosed late when complication are present. Dunning (2004) described it as a long term complication with neuropathy, cardiovascular disease and retinopathy. It is a universal metabolic disorder affecting more than 2 million people in the United Kingdom and up to 750,000 more are expected to have it without knowing they do. Studies conducted show that 80% of population affected by diabetes live in developing and underdeveloped countries and the majority of people with diabetes is between 40 to 59 years of age. It is also estimated that 183 million people (50%) with diabetes are undiagnosed. It is noticed that Diabetes caused 4. million deaths in 2011 and caused sharp increase in medical expenditure. I am a staff nurse working in the cardiac ward and we often receive patients with cardiac problems as a long term complication of type 2 diabetes. Cardiovascular disease is a major cause of hospital admission and mortality in people with diabetes. Most of them are not diagnosed until they are admitted. During the course of this study the medical history and care and treatment provided to a patient named Mr M Davies who was admitted in my ward is chosen to learn about managing and reducing cardiovascular disease among patients with type 2 diabetes. In 1998 UKPDS pointed out the importance of reducing lipids blood pressure and blood Glucose to reduce the risk of cardiovascular disease. Hypertension leads to thicker, less elastic blood vessel walls and increase the strain on the heart. Studies indicated that there is a linear correlation between the diastolic blood pressure and the eventual outcome of type 2 diabetes. Standl & Schnell (2000) pointed out that as a result of ischemia-induced remodelling subtle changes occur in the heart and the effects of hyperglycaemia on the endothelium of large blood vessels that causes heart to failure. Mr M Davies (Mr.  MD) is a 61-year-old pensioner with a 4 years history of type 2 diabetes. He was diagnosed in 2008 and he had symptoms of hyperglycaemia for 2 years before diagnosis. His fasting blood glucose records indicated values of 6–7 mmol/L, which were explained to him as symptomatic of â€Å"borderline diabetes. † During the preliminary diagnosis, he was advised to reduce weight (â€Å"at least 10 lb. †), but no further action was taken. Other medical problems include obesity and hypertension. He was admitted in the ward with recurrent chest pain. (Appendix 1) This assignment is about managing and reducing cardiovascular risk in type 2 diabetes mellitus. Heart disease is well acknowledged as a chronic problem of diabetes, and is the major reason of morbidity and mortality in patients from middle-age onwards. Type 2 diabetes is associated at the onset with risk factors for heart disease such as hypertension and obesity, raising the question of whether diabetes is the independent risk factor for heart disease. In 2001 Morrish et al pointed out that the majority of cardiovascular deaths are specifically due to heart disease and this is supported by Fisher, Miles, (2008) commenting that heart disease is the major cause of morbidity and mortality at young as well as older ages. Butler (1997) said that increased life expectancy has led to an increase in the number of people over 65 years of in both the developed and developing worlds. Marso (2003) pointed out that due to the clear association between age and the development diabetes, this increase in the number of older individuals in the population will inevitably contribute to the increased prevalence of diabetes. Watkins (2008) mentioned that Type 2 diabetes is a disease of relative prosperity, prosperity leads to overweight and physical indolence. Insulin resistance, increasing with obesity, associated with progressive failure of insulin secretion in relation to ageing underlies the development of diabetes. It is anticipated that by 2025 the number of people with type 2 diabetes will be around 380 million and people with impaired glucose tolerance will be around 418 million. Diabetes is the foremost global cause of premature mortality that is broadly underestimated, because only a few among the diabetic patients die from reasons uniquely related to the condition. Nearly one half of type 2 diabetes patients die prematurely of a cardiovascular reason and approximately 10% die of renal failure. Diabetes is a condition that required to be managed every day. The management of Diabetes can refer to dealing with short term measures like high and low blood sugar to regulating it over the long term for instance by attaining to grips with knowing the condition. All patients with Type 2 diabetes require active dietary management throughout their disease. Watkins (2008) pointed out that weight loss in the obese is extremely valuable but is separate from dietary manipulations to control blood glucose. Treatment typically includes diet control, exercise, monitoring blood sugar at home, and in some cases, oral medication and/or taking insulin. Based on the type diabetes medicines are classified into different groups and each category of diabetes pills functions differently. Commonly used medicines to control diabetes are Sulfonylureas, Thiazolidinediones, Biguanides, Alpha-glucosidase inhibitors, Meglitinides and, Dipeptidyl peptidase IV. Sulfonylureas reduce blood sugar by stimulating the pancreas to produce more insulin. Sulfonylureas medicines like Glimeperide, Gliclazide,. Biguanides improve insulin’s capacity to transfer sugar into cells particularly into the muscle cells. They also stop the liver from releasing stored sugar. Biguanides are not advised to be used in people who have heart failure or kidney damage. Biguanides medicines such as Metformin. Thiazolidinediones like Pioglitazone and Rosiglitazone enhances effectiveness of insulin in muscle and in fat tissue. Alpha-glucosidase inhibitors, such as Precose (acarbose) and Glyset (miglitol) prevent enzymes that help digest starches, reducing the rise in blood sugar. These medicines may cause diarrhea or gas. They can decrease hemoglobin A1c by 0. 5%-1%. Meglitinides, like Prandin (repaglinide) and Starlix (nateglinide) reduces blood sugar level by stimulating the pancreas to secreate more insulin. Dipeptidyl peptidase IV (DPP-IV) inhibitors, such as Januvia (sitagliptin), Onglyza (saxagliptin), and Tradjenta (linagliptin) lowers blood sugar level in patients with type 2 diabetes by accelerating insulin secretion from the pancreas and lowering sugar production. The case history of Mr. MD indicated that he was advised to manage blood sugar level by diet control and regular exercise. It was also advised to take metformin 1000mg twice a day when diet and exercise are not enough to manage blood sugar level. The history showed that Mr. MD was non-compliance with any of these. On admission his random blood sugar was 20 mmol/L. As he was unable to tolerate oral intake due to nausea and chest pain, GKI was commenced for a day to control his blood sugar. On second day his blood sugar level was controlled and he started eating and drinking normally. Mr MD was referred to diabetic specialist nurse and dietician . Diabetic specialist nurse advised to stop GKI and advised to start OHA. Mr. MD commenced on metformin 1000mg three times a day (Learning outcome 1). Metformin has long been accepted as a appropriate first-line choice of oral medicine for Type 2 diabetes as it is the only oral hypoglycaemic agent related with no weight gain or even weight reduction. They decrease hepatic gluconeogenesis, boost peripheral glucose uptake and also lower the absorption of carbohydrate from the gut lumen. Because metformin functions on insulin sensitivity and with only endogenous glucose stimulated insulin secretion, it virtually never causes hypoglycaemia on its own and patients using it with diet and exercise do not need routinely to self-monitor blood glucose. The UK Prospective Diabetes Study (UKPDS, 2002) demonstrated a significant survival advantage for Type 2 patients started on metformin as first-line therapy, with less cardiovascular mortality, although it should be noted that they only used the drug in obese patients. Obesity is a worldwide problem. Barnett (2009) pointed out that obesity and overweight are independent risk factors for cardiovascular morbidity and mortality. Various studies reveal that obesity is a major cardiovascular disease risk factor across world’s populations. Risk of morbidity and mortality begins to increase at body mass index (BMI) >25 kg/m 2 and the risk raises sharply at BMI >30 kg/m 2. Each kilogram of weight put on from the age of 18 years was linked with 3. 1% higher risk of cardiovascular disease. In 1998 Gunnell observed that over weight in adolescence is a forecaster of these dangers in adulthood . These finding were supported by Must in 1992,who explained that this increased risk extends to overweight children and adolescents, who may be at risk of premature cardiovascular morbidity and death. The mechanism by which obesity causes increased cardiovascular morbidity and mortality is attributed to associated co-morbidities and risk factors such as hypertension, dyslipidaemia, type 2 diabetes and insulin resistance. The co-occurrence of some or all of these risk factors along with obesity is termed the cardiometabolic syndrome. On examination it was noticed that Mr.  MD has a high BMI (30. 9). West (2007). Suggested that addressing obesity is an essential aspect of managing diabetes, because type2 diabetes and many other health problems coexist. However it is important to consider the individual’s specific nutritional needs rather than just providing them with a ‘weight loss plan,’ ‘diabetic diet,’ a ‘standard meal plan or information about healthy eating. ’ Mr. MD was referred to the dietician. Dietician gave dietary advice and educated about importance of weight management by diet and regular exercise. He was advised to avoid take-away foods, reduce alcohol consumption and taking balanced food to prevent hypo and hyper glycaemia (Learning outcome 1).. Hypertension-Prevention & Management is very important in the management of metabolic diseases. In 1985 Modan et al pointed out that there is a strong relationship between high blood pressure and insulin resistance. This findings is supported by Reaven, (1999) . He said that the prevalence of insulin resistance in hypertension has been estimated at 50%. Scheen, (2004) proposed several possible mechanisms for this. Coutinho et al. (1999) said that impaired fasting blood glucose is related with high cardiovascular risk particularly if accompanied by hypertension. Henry et al. , (2002) said that in people with diabetes, cardiovascular disease risk is increased two to fourfold compared with those with normal glucose tolerance. This was supported by the study conducted by Heffner et al. , (1998) who said that diabetic people without past history of myocardial infarction may have as high a risk of myocardial infarction as non-diabetic patients with a history of previous myocardial infarction. Non-pharmacological interventions are cheap than pharmacological interventions and have no known dangerous effects. A range of lifestyle changes reduce blood pressure and the occurrence of hypertension. Non-pharmacological interventions such as weight loss in the overweight, exercise programmes, limiting alcohol intake and a diet with increased fruit and vegetables and limited saturated fat content, minimising dietary sodium consumption and increased dietary potassium intake. From the medical history of Mr MD it is noticed that he was taking Ramipril 5 mg/day and bisoprolol2. mg/daily. It is established that where non-pharmacological interventions are not enough to achieve the objectives then Pharmacological interventions are required. Several drug treatments are of proven value in minimising cardiovascular risk in people with diabetes and hypertension. Low-dose aspirin is suggested in diabetes whether or not there is evidence of large vessel disease. Williams et al. , (2004) noticed that the British Hypertension Society recommends 75 mg of aspirin for all with hypertension and diabetes, unless contraindicated. Antihypertensive therapy diminishes the risk of macrovascular complications by around 20%. Reducing blood pressure reduces progression of retinopathy, albuminuria and progression to nephropathy. Staessen et al. , (1997) observed that clinical trials with ACE inhibitors, beta-blockers, diuretics, angiotensin receptor blockers and calcium channel blockers have demonstrated benefit of treatment of hypertension in type 2 diabetes (Learning outcome 1).. On admission blood pressure level of Mr MD was very high. He was recommended treatment with antihypertensive drugs. Consultant prescribed Losartan 100 mg/day and increased ACE inhibitor (ramipril 10 mg/day) and beta-blocker (bisoprolol 5 mg/dayl). Studies show that treatment with ramipril in addition to standard therapy minimised combined myocardial infarction, stroke and cardiovascular death by about 25% and stroke by 33% compared with placebo plus conventional methods. This was supported by Sowers and Haffner, (2002) saying that almost all patients with hypertension and diabetes require combinations of blood pressure reducing drugs to attain the recommended blood pressure targets. During the treatment Mr. MD was advised non-pharmacological methods of blood pressure management and importance of diet control and referred to cardiac rehabilitation for regular exercise. Management of high cholesterol plays an important role in the management of diabetes. Lipid abnormalities are common in type 2 diabetes and can be broadly categorized into two groups: those that are common to the general population, for example elevated total and LDL cholesterol; and additional diabetes-related abnormalities, for example elevated triglycerides and reduced HDL cholesterol. Current US and European guidelines emphasize reducing LDL-C level to less than 100 mg/dL (2. 59 mmol/L). To reduce the cholesterol Mr. MD was undergone intensive lipid-lowering treatment with atorvastatin 80 mg/day. Dietary therapy was also a part of the treatment which was found effective to lower Lipids. Interventions to stabilize lipids in order to decrease the risk of CVD are warranted in people with type 2 diabetes. Both Fibrates and Statins improve lipid profiles in people with diabetes. Many studies have established the safety and effectiveness of the fibrates (gemfibrozil, bezofibrate, fenofibrate) in diabetes. Fibrates stimulate the peroxisome proliferator-activated receptor-a, changing the expression of a number of enzymes that regulate lipid metabolism, including lipoprotein lipase. Statins inhibit hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is rate restrictive in cholesterol production. Another major strategy in the management diabetes is lifestyle interventions. Lifestyle interventions can progress lipid levels. Studies conducted on weight loss and lipids in type 2 diabetes have varied greatly as to the study diet, design and duration. A Meta-analysis of 89 studies and 1800 subjects with type 2 diabetes reported that a weight loss of 5% or greater reduced triglyceride levels by 10 ±40% and total cholesterol by 5 ±15%. These effects were greatest with very low-calorie diets, and the effects were seen in studies up to 6 months. A variety of diets can alter the lipid profile in people with type 2 diabetes. The organisation of diabetes care is very important in the long term management of diabetes care. Diabetes is the significant disease confronting the United Kingdom’s (UK) health care system. As a result, understanding how best to manage diabetes facilities is an important area if the health system is going to deal with the growth in both the demand for and cost of diabetes treatment. Care should be planed at reducing symptoms and minimizing the danger of long-term problems. It is pointed out that a proper balance of glucose and other cardiovascular risk factors such as smoking, hypertension, inactive lifestyle, dyslipidaemia and obesity is very crucial (UKPDS, 2002) in the organisation care of diabetes.

Gaius Mucius Scaevola

Gaius Mucius Scaevola is a legendary Roman hero and assassin, who is said to have saved Rome from conquest by the Etruscan king  Lars Porsena. Gaius Mucius earned the name ‘Scaevola’ when he lost his right hand to Lars Porsenas fire in a show of intimidating will power. He is said to have burned his own hand off in the fire to demonstrate his bravery. Since Gaius Mucius effectively lost his right hand to the fire, he became known as Scaevola, which means left-handed. Attempted Assassination of Lars Porsena Gaius Mucius Scaevola is said to have saved Rome from Lars Porsena, who was the Etruscan King. In about the 6th century B.C., the Etruscans, who were led by King Lars Porsena, were on a conquest and were trying to take Rome. Gaius Mucius supposedly volunteered to assassinate Porsena. However, before he was able to successfully complete his task he was captured and brought before the King. Gaius Mucius informed the king that although he might be executed, there were plenty of other Romans behind him who would try, and eventually succeed, in the assassination attempt. This angered Lars Porsena as he feared another attempt on his life, and thus he threatened to burn Gaius Mucius alive. In response to Porsena’s threat, Gaius Mucius stuck his hand directly in the burning fire to demonstrate that he did not fear it. This showing of bravery so impressed the King Porsena that he did not kill Gaius Mucius. Instead, he sent him back and made peace with Rome. When Gaius Mucius returned to Rome he was viewed as a hero, and was given the name Scaevola, as a result of his lost hand. He then became commonly known as Gaius Mucius Scaevola. Gaius Mucius Scaevola’s tale is described in the Encyclopedia Britannica: â€Å"Gaius Mucius Scaevola is a legendary Roman hero who is said to have saved Rome (c. 509 bc) from conquest by the Etruscan king Lars Porsena. According to the legend, Mucius volunteered to assassinate Porsena, who was besieging Rome, but killed his victim’s attendant by mistake. Brought before the Etruscan royal tribunal, he declared that he was one of 300 noble youths who had sworn to take the king’s life. He demonstrated his courage to his captors by thrusting his right hand into a blazing altar fire and holding it there until it was consumed. Deeply impressed and fearing another attempt on his life, Porsena ordered Mucius to be freed; he made peace with the Romans and withdrew his forces. According to the story, Mucius was rewarded with a grant of land beyond the Tiber and given the name Scaevola, meaning â€Å"left-handed.† The tale is presumably an attempt to explain the origin of Rome’s famed Scaevola family.†