Chronic Pain Management: An Insight Into Neuropathic Pain

Chronic Pain Management: An Insight Into Neuropathic Pain Many people suffer from chronic pain. In these patients, the most common wish is to be pain free. Even though modern Medicine has advanced at an unprecedented rate over the past century, approaches to chronic pain management is still not completely satisfactory. I have recently seen a patient who has been living with neuropathic pain for many years. Neuropathic pain is a type of chronic pain that is considered to be the most difficult to treat and manage, due to its complex nature in etiology and clinical manifestations. Despite the improvement in scientific understanding of pathogenesis of neuropathic pain, and utilization of newer pharmacological, surgical and cognitive approaches, diagnosing and treating neuropathic pain still poses a challenge clinically. This essay will be presenting a case history of a patient with neuropathic pain being treated at the Kent and Canterbury Hospital and this case will form the basis of discussion on the current understanding of neuropathic pain m echanisms and its management. Patient case Mrs L is a 58 years old medically retired office worker who has a 25-year history of multiple sclerosis. She has been coping well until 8yrs ago when her left foot suddenly experienced a shooting pain on weight bearing. At first, she was maintained on paracetamol and nurofen by her GP with limited pain relief and then referred to the podiatrist, where an ultrasound scan revealed the presence of Mortons neuroma (a benign swelling of the intermetatarsal plantar nerve causing neuropathic pain), which was causing intense pain with a severity 10/10 across her left forefoot. To help alleviate the pain, it was initially decided that surgically removing the neuroma could achieve adequate pain relief, but this was proven to be an unrealistic goal. During the surgical intervention period, she had altogether three neuromas removed on separate occasions, with additional shaving off the bones to reduce compression on the nerve and resultant inflammation. She was then referred to be managed at the pain clinic. While Mrs L has been under the care of the pain physicians, she was given local anaesthetics steroid infiltration into her forefoot, cryotherapy (ice cold packs applied to tibial nerve), guanethedine block, lumbar chemical sympathectomy (with midazolam fentanyl), acupuncture, lidocaine patches, capsaicin cream, duloxetine and co-codamol. Despite temporary pain relief provided by these therapies, there was not a long-lasting effect that allowed Mrs L to stay pain-free. Understandably, living with an excruciating pain chronically can severely damage an individuals psychological as well as physical health. She could no longer enjoy her hobbies, such as dancing and going to antic fairs; even daily activities such as shower would make her scream in pain. As a result, she became extremely depressed and suicidal. Currently, she is receiving a multidisciplinary input from her GP, the specialist pain physician, specialist pain nurse, clinical psychologist, and physiotherapists and is maintained on gabapentin and diclofenac for her neuropathic pain, citalopram for her slowly recovering depression and baclofen for controlling her ongoing multiple sclerosis symptoms. She is also regularly attending chronic pain management programs, through which she believes that she gains better appreciation for her condition and is in a better position to be in charge of her own symptoms. This case nicely demonstrates the difficulties encountered in clinical practice in treating chronic pain. First of all, neuropathic pain is exceptionally difficult to treat, with unpredictable outcomes; secondly, most methods of pain management can only provide symptomatic relieve of pain temporarily, rather than offering a permanent cure; thirdly, chronic pain is an extremely debilitating condition to live with and its psychological impact should not be underestimated; and finally, to enable the best pain management a multidisciplinary approach is evidently the most successful and gives the patient most control over their symptoms. What is pain? We are all familiar with the term pain. The International Association for the Study of Pain (IASP) defines pain as: An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. (IASP 2007). It is important to note that pain is a very subjective experience, which varies enormously from one individual to the next. To emphasize on the subjectivity of pain perception and the need for individualized approach to pain management, Margo McCaffery who specialized in pain management nursing in 1968 described pain as whatever the experiencing person says it is, existing whenever the experiencing person says it does (Rosdahl Kowalski, 2007). It is undeniable that psychology and physiology are interwoven in the perception of pain. To understand pain, it is helpful to know what causes pain; as mentioned above, normally our perception of pain is triggered by a specific stimulus, such as hot, cold, or sharp objects, which could cause potential tissue irritation or injury. It is obviously advantageous in evolutionary terms to be able to sense the potential cause of injury and act via spinal reflexes to achieve self-protection, e.g. withdrawal of fingers from hot pan. This form of pain is called nociceptive pain, where the stimulus is known to be harmful in nature. This type of pain warns us of impending damage; therefore, it is regarded as the good type of pain. Of course, most of the long-term pains are certainly not good or friendly. What distinguishes between friend and foe in the field of pain is determined by the time-course, the intensity, the cause of and the social and economic consequences of the pain. An excellent example of a bad pain is neuropathic pain (Figure 1): Figure 1. Diagram showing the mechanisms behind the processing and perception of three different types of pain. Phase 1= nociceptive pain; Phase 2= inflammatory pain; Phase 3= neuropathic pain. (Cervero F, 2009) Neuropathic pains are resulted from disease or trauma to the central or peripheral nervous system; common causes include stroke, spinal cord injury, multiple sclerosis, surgery, diabetic neuropathy, and herpes zoster virus (Jensen et al., 2007). The Neuropathic Pain Special Interest Group (NeuPSIG) of the IASP has recently redefined neuropathic pain as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system (Treede et al., 2008). As a result, neuropathic pain produces very unusual pain sensations beyond the range produced by the normal nociceptive system; these include spontaneous pain, reduced pain thresholds, and mechanical allodynia (Cervero F, 2009). As illustrated in figure 1, abnormal sensory processing is one of the landmarks for diagnosing neuropathic pains; patients often experience pain in the absence of any noxious stimuli (allodynia) and additionally produces an abnormally heightened sensory input, changing a non-noxious stimulus int o a painful stimulus, producing a state called hyperalgesia. Therefore, the main characteristic is the nearly complete lack of correlation between peripheral noxious stimuli and pain sensations perceived. There are many types of neuropathic pain (Table 1), which can be broadly classified into four groups based on their aetiology and anatomy: peripheral nervous system focal and multifocal lesions, peripheral nervous system generalized polyneuropathies, central nervous system lesions, and complex neuropathic disorders (Freynhagen Bennett, 2009). It is outside the scope of this essay to discuss these different types of neuropathic pain in further detail; rather, neuropathic pain as a distinct group of pain will be explored. Table 1. Examples of neuropathic pain syndromes (Freynhagen Bennett, 2009). How is neuropathic pain diagnosed? Despite its frequent occurrence, neuropathic pain still constitutes as a major diagnostic problem in clinical practice because it can present with a variety of signs and symptoms, which vary greatly even within one particular disease entity (e.g. in postherpetic neuralgia) (Geber et al, 2009). Clinical examination and expert judgment is still the best way to make a clinical diagnosis of neuropathic pain, despite the recent development of various screening tools, such as the LANSS questionnaire (Bennette, 2001) and the Neuropathic Pain Scale (Galer and Jensen, 1997) that assist in making a diagnosis. Bedside examinations for hyperalgesia and dysthesia include assessing the effect of the same stimuli on painful areas compared to the contralateral side or an unaffected site. Allodynia is demonstrated by the experience of pain when performing light touch with cotton wool; exaggerated painful response to pin prick suggests hyperalgesia, therefore lowered pin-prick threshold. These are the typical components that define a pain as neuropathic type. Patients are most likely to present with a mixture of pain types with a neuropathic component to it. It is important to identify the presence of such a component as the treatment recommendations are different for these. With the introduction of the new grading system for neuropathic pain by NeuPSIG group (Treede et al 2008), it is becoming increasingly recognized that chronic pain is often presented as a combination of different types of pains, rather than a clear-cut nociceptive or neuropathic type of pain. In Treede and colleagues new recommendation for the diagnosis of neuropathic pain, options of definite, probable or possible are available for the diagnosis of a component of neuropathic pain in the disease presentations in the clinical setting, which aims to aid more accurate diagnosis of neuropathic pain (Figure 2). Figure 2. Flow chart of grading system for neuropathic pain. The grading system is based on four criteria: pain distribution (criterion 1), the link between pain distribution and the patients history (criterion 2), confirmatory tests of neurologic status demonstrating positive or negative sensory signs confined to the innervation territory of the lesioned nervous structure (criterion 3), and further confirmatory diagnostic tests to identify the lesion or disease entity underlying the neuropathic pain (criterion 4). Criteria 1 and 2 must be met to initiate the working hypothesis of possible neuropathic pain. *Patient requires follow-up and/or additional confirmatory tests. à ¢Ã¢â€š ¬Ã‚  The point at which the diagnosis of possible neuropathic pain should be abandoned has not been defined (Treede et al 2008). Mechanisms of neuropathic pain Broadly speaking, neuropathic pain arises from the peripheral nervous system (ectopic impulse generation due to abnormal sodium channel expression), or from the central nervous system (central sensitization, disinhibition and plasticity) (Scadding, 2003). The key behind the generation of neuropathic pain is the abnormal neurological changes to the sensory system resulting in an abnormal hyperalgesic state, achieved through three processes: 1) the activation and sensitization of peripheral nociceptors, which are responsible for sensing peripheral noxious stimuli; 2) the abnormal amplification, rather than the suppression as in the normal states, of the central nervous system, known as central sensitization, caused by the strengthening of the synaptic connections between the peripheral and central nervous systems, producing a persistent pain state; 3) the change in the central actions of the undamaged afferents, so that a non-noxious tactile stimulus sensed by these receptors are converted into nociceptive information and processed as pain, rather than a light touch (Cervero F, 2009). This also further leads to secondary hyperalgesia, which means that instead of relieving the nociceptive pain by rubbing on the painful area (tactile stim ulus), the tactile movement of rubbing will actually produce the opposite effect of enhancing the existing pain. Figure 3. The pain signaling and modulation pathways. F Cx: frontal cortex; SS Cx: somatosensory cortex; Hyo: hypothalamus. (Ro Chang, 2005) As shown in Figure 3, the physiological pain mechanisms include the pain signaling pathway from nociceptors to peripheral nervous system to spinal dorsal horn cells to thalamus and finally to the cortex, and the pain control system from the cortext to periaqueductal grey to raphe nucleus to spinal dorsal horn (Ro Chang, 2005). In normal circumstances, there is a balance between signal transduction and pain modulation, therefore the individual recovers from that episode of pain. However, when this balance is disturbed, i.e. when there is a lesion within the primary somatosensory system, then the individual experiences neuropathic pain. The lesion may occur anywhere along the pathways of the somatosensory system, and it could be as a result of compression, inflammation, ischaemia, trauma, tumour invasion, nutritional deficits, or degenerative processes to the neurons (Ro Chang, 2005). Some of these important mechanisms will be discussed individually below. Local nerve injuries After the occurance of local nerve damage, in an attempt to repair, a neuroma forms at the proximal stump of the damaged nerve. A neuroma is a tangled mass of regenerating axons embedded in connective tissues. The axons within a neuroma not only fail to regenerate properly, but also develop abnormal electrical activities (England et al, 1996). This neuroma sprout then begins to fire abnormal signals with a heightened excitability, which stimulates regenerating C-fibers. After a period in the growth of these fibers, erratic impulse generator will develop, which sends abnormal signals into the central nervous system, perceived as dysthesia, parasthesia, itching or electrifying sensations (Liu et al, 2002). Sodium channel accumulation Sodium channel density is increased in areas of axons proximal to the injury site, as shown by England et al (1996) when the excised neuromas were studied from patients who suffered from painful traumatic neuromas (Figure 4). This specific type of sodium channel accumulated have a faster recovery time after inactivation, therefore, they are able to conduct ectopic impulses in neuropathic states. The ectopic activity then maintains the central sensitization process, resulting in great amplification of peripheral afferent signals. In neuropathic pain, there is a change in ionic channels composition and functions, such an accumulation of sodium channels which leads to hyperexcitability of these nerve terminals. These are found to be accumulating in neuropathic damaged areas of the nerve, such as in neuromas and demyelinated areas (Devor, 2006). In a normal axon, the transportation of sodium ion channels is preprogrammed via endoplasmic vesicles along the axons to be distributed in the n odes of Ranvier and peripheral sensory endings; there is a low density of sodium channels on the myelinated axonlemma. However, as a consequence to neuropathic damage, the set program of ionic channel settlement is disturbed, and these ion channels end up being located at a high concentration at the areas of neuromas, demyelination and sprouting (Aurilio et al, 2008). Such important roles played by sodium channels means that by blocking these channels, neuropathic pains could be reduced. Indeed, sodium channel blockers open up a major therapeutic channel for neuropathic pain treatment. Figure 4. Sodium channel immunocytochemistry of neuromas. (a, b, c) Sodium channel-specific immunoreactivity is present throughout the axons of th these neuromas. (d) Control showing the nonspecific immunofluorescence. Scale bar = 10 micrometer (England et al, 1996). Calcium channels and signaling in injury Calcium channels are also involved in contributing to neuropathic pains, as intracellular calcium determines the phosphorylation of the membrane proteins (Aurilio et al, 2008). The inflammatory neuropeptides, calcitonin gene-related peptides (CGRP), are released from injured nerve endings. They have a role in acting as co-transmitters in the spinal cord, therefore are involved in the central sensitization and hyperalgesic states found in neuropathic pain. An in vitro study identified that the release of CGRP entirely depended on the presence of extracellular calcium ions; this process involves particularly the N- and L-type calcium channels (Kress et al, 2001). Selective calcium channel blockers, such as gabapentin and lamotrigine may have significant potential in treating neuropathic pain. Cytokines in neuropathic pain Cytokines such as interleukins and tumour necrosis factors are well known mediators of inflammatory responses. Additionally, they are involved in neurogenic inflammations and are thought to play a role in the generation of neuropathic pains. In an established experimental model of neurogenic hyperalgesia and allodynia, mice with chronic constrictive injury to one sciatic nerve, the usage of interleukin-1 antagonist has been found to significantly yield in a reduction in the pain responses (Sommer et al, 1999) (Figure 5). Since TNF- Ã‚ ¡ immunoreactivitiy is found to be higher in nerve biopsies from patients with neuropathic pain, directing treatments to reducing the level of cytokines in the nervous system may also be helpful in relieving neuropathic pains (Empl et al, 2001). Indeed, combined neutralizing therapies against IL-1 and TNF- Ã‚ ¡ produced additive effects in experimental models (Schafers et al, 2001). Figure 5. Hyperalgesia to thermal stimuli following unilateral sciatic nerve injury in six groups of mice. a negative difference score is an indicator of hyperalgesia in the experimental/treatment limb. Hyperalgesia is present throughout the experimental period in the sham-treated group of mice. Treatment with anti-IL1 reduces hyperalgesia in a dose dependent manner (Sommer et al, 1999). Central inhibition inefficiency and sensitization The pain transmission system is under continuous inhibitory control from the brainstem centers, such as periaqueductal grey and locus coeruleus. Many studies have been conducted in laboratory animals for studying the pain mechanisms in neuropathic pain. It is found that in animals with neuropathic pain their central descending inhibition is nearly 50% lower than normal (Zimmermann 2001). Additionally, there is a hypersensitized central nervous system in neuropathic pain. Normally central sensitisation process would return back to baseline level when the tissue heals and inflammation subsides (Dworkin et al, 2003), but in neuropathic pain states this is not the case. The plasticity and sensitisation following peripheral nerve injury was thought to be caused by the long-term potentiation mechanism (Liu Sandkuhler, 1995). It is thought that after local nerve damage peripherally, growth factors such as nerve growth factors (NGF) can no longer be taken up into the dorsal ganglion neurons; this alters the nervous system at the transcription and protein synthesis level. NGF is a trophic molecule essential in the development maturation of the nervous system, and it is found to be elevated in conditions which pain is a predominant feature. This change to the composition to the nervous system also results in changes in the activities of aspartate and NMDA, which leads to an i nflux of calcium ions that indirectly contributes to the sensitisation and hyperalgesia of the spinal cord dorsal ganglion cells (Ro Chang, 2005). Peripheral inhibition inefficiency In addition, there also is a reduction in the response to endorphin molecules in patients with neuropathic pain than other pain mechanisms (Terenius 1979); therefore, there is a reduction in the sensation of pain relief centrally. Peripheral nerve lesion was simulated in rats by rhizotomy, a technique which severs the spinal roots, and this has demonstrated a decreased opioid receptor binding in the spinal cord (Zajac et al, 1989). Living with neuropathic pain From a patents perspective, pain is something they have to learn to live with, however bad it is. Patients who suffer from chronic pain not only have to go through the physical anguish exerted by the pain, but being in pain also hinders them from normal day to day functioning; from not being able to stay independent or taking care of themselves, to losing jobs, family and friends, lack of support and results in social isolation. A patient has once told me that: because what Im going through (pain) is not readily recognized by others, the way other people acted towards me put me under lots of frustration and made me socially unaccepted. It is crucial to bear in mind the wider impact of living with neuropathic pain when formulating a management plan for that individual. Not surprisingly, neuropathic pain is linked to significant reduction in the patients health-related quality of life (HRQoL) as well as creating substantial costs to the health service. It is reported that generally, patients with neuropathic pain have higher pain rating scores and lower HRQoL (Jenson et al, 2007). In a cross-sectional evaluation of the impact of neuropathic pain on patients and their quality of life conducted in the Spanish population, it was found that pain substantially interfered with work and family life in these patients. Over 95% of the 1519 patients recruited for this study had either neuropathic pain or a mixed neuropathic and nociceptive pain. Younger patients tend to report a lower quality of life than that of the elderly population in both the physical and mental components of life (Figures 6a 6b); possibly due to having fewer comorbidities in younger patients helps to exaggerate the perceived deleterious effects of neuropathic pain on their daily functioning. Using the Sheehans disability scale, the younger patients are also shown to have generally a higher perceived stress compared to the older patients (Galvez et al, 2007). It is important to analyse the effects that neuropathic pain exerts upon its sufferer, not only because we start to appreciate the level of impairment on the quality of life this chronic illness can cause to the patients, but also to further explore areas that could be perhaps better dealt with in terms of treatment (Jenson et al, 2007). As was reflected by the outcome of the Spanish study, 43% of patient had extreme disability; these included disability for work (51%), 47% for social life, 42% for family life. 38% of the patients also reported extreme stress and 19% perceived that they received little or no social support (Galvez et al, 2007). This shows that living with neuropathic pain is not just leading to physical disability, but also psychological and social dysfunctioning. Having known this nature of neuropathic pain, it important to consider both a pharmacological and psychosocial approach when prescribing treatment and formulating management plans. Figure 6. Scatter graph showing the linear relationship between age (years) and quality of life of the patient; physical (6a) and mental (6b) components, given as a standardised score relative to the reference Spanish population (SDS). SDS score is shown for each patient adjusted for type of neuropathic pain, center, and present pain intensity, age, and sex. SD, standard deviation; 95% CI, 95% confidence interval. (Galvez et al, 2007) b. a. Management of neuropathic pain The management of neuropathic pain involves a number of well-established pharmacological therapies, as well as utilizing the psychosocial aspects of the neuropathic pain nature fully to best control the patients pain symptoms. Non-Pharmacological approaches As the symptoms of pain are not just derived purely from a physical entity, psychotherapy should be considered as part of the management program for neuropathic pain. At an early stage, patients should be educated on the nature of the condition and to have realistic expectations with regards to treatment options; especially the current management for neuropathic pain is still mainly palliative in nature, with main aims to reduce symptomatic complaints of pain, but not a curative fix. To be able to alleviate the pain and achieve symptomatic relieve, even if only temporarily, may be the only attainable goal (CREST, 2008). Since non-pharmacological treatments have the lowest risks of adverse side effects these must be offered early. These include a combination of physiotherapy, occupational therapy, psychotherapy and pain management programs that are adjusted to the individuals psychological and physical needs. The main aims for physiotherapy is to provide pain relieve wherever possible, but also focuses on the restoration of normal functioning and helping the patient to return to normal physical activities, such as going back employment (Serpell et al, 2008). The low risk physiotherapy modalities include TENS (transcutaneous electrical nerve stimulation) and acupuncture are offered, along with appropriate education, advice and exercise. Functional difficulties in areas of personal care, work and leisure could be managed best by the input of occupational therapists, who may work around the needs of the individual in adjusting the arrangements at home/work to best allow the patient to function despite t he pain. In Mrs Ls case, she had shower rails and hand-held tools to pick up distant objects without exerting strain on her back/affected limbs; these were extremely helpful to her. Of course, to maximize the outcome of pharmacological treatment, psychological therapy is essential in addressing the disability, emotional impacts and general life interruptions that are consequences of neuropathic pain. Apart from pharmacotherapy, psychotherapy is the best evidence-based therapy for the treatment of chronic pains like neuropathic pain (Morley et al, 2000). Additionally, patients living with chronic pain often suffer from other comorbidities. Frequently these are not treated alongside the treatment for the chronic pain, therefore, a limited effect of the pain treatment may be observed. Behavioral and psychiatric conditions are especially common in patients with neuropathic pain; recognizing and treating these will aid in improved quality of life and better pain relief overall (Fishbain, 1999). An recent eight-week study of the effects of cognitive behavioural therapy (CBT) on chronic pain-induced insomnia has found that patients who received CBT exhibited significant reductions in sleep latency, number of awakenings during sleep and overall quality of sleep (Jungquist et al, 2010). This offers further hope for patients who suffer from pain-related insomnias. Finally, the Pain Management Program is a multi-disciplinary approach to pain control that is tailored to each patients individual needs. Patients are typically referred to this program if they have been living with chronic pain for a number of years and suffer from significant physical, social and psychological functional difficulties. Many have become dependent on medications and acquired a number of side effects from these medications which are slowly eroding the quality of their lives. In the pain management programs, the goals are to reduce the subjective experience of pain, learning new coping strategies to control pain and improve physical and emotional functioning. Indeed, the pain management programs have been found to achieve a reduction in medication and enhanced rates of returning to work (CREST 2008 NRH 2009). Pharmacological therapies for neuropathic pain In most cases, patients with neuropathic pain will need to be started on analgesic medication after failure to respond to non-pharmacological treatments. Although opioid and non-opioid analgesics, such as codeine and diclofenac respectively, have a role in dampening pain transmission in within the CNS in neuropathic pain states, it is far more effective to target the sodium, calcium and NMDA receptors, which are altered during nerve injury. Generally speaking, the clinical effectiveness of these drugs is limited by their narrow therapeutic indexes, i.e. the difference between the number needed to treat (NNT) and the number needed to harm (NNH) is very small (Rice Hill, 2006). Neuropathic pain is appreciably a very complex condition and treatment for this can be a real challenge, as most patients do not respond to conventional analgesics. The main problems lie within the inadequate diagnosis, lack of understanding of the pain mechanisms, inappropriate selection of therapies, and insufficient management of comorbidities that could delay the response to neuropathic pain therapies (Ro Chang, 2005). Recently a review of the guidelines by OConnior Dworkin has resulted in the formulation of a stepwise approach to neuropathic pain management in primary care (Table 2). It is important to highlight that the first step of the management plan includes the identification of comorbidities, and relevant patient education as discussed above in the non-pharmacological managements of neuropathic pain to fully prepare the patient for adequate treatment. Table 2. Stepwise pharmacologic management of neuropathic pain (OConnor Dworkin, 2009) According to a recent review and recommendation by Dworkin et al, three lines of pharmacological treatment have been advised for neuropathic pain treatment. The first line treatments include tricyclic antidepressants (TCA), selective serotonin noradrenaline reuptake inhibitors (SSNRI), Ca2+ channel ligands (e.g. gabapentin pregabalin) and topically applied 5% lidocaine; second line treatments including opioid analgesics tramadol; and third line treatments are the other antiepileptics (e.g. Carbamazepine, lamortigine), other antidepressants (e.g. citalopram), N-methyl-D-aspartate (NMDA) antagonists and topically applied capsaicin (Dworkin et al, 2007 and OConnor Dworkin, 2009). TCAs The administration of TCAs such as amytriptyline and nortriptyline will benefit patients with neuropathic pain as TCAs have been shown consistently to be more efficacious than placebos in a number of randomized controlled trials (Saarto Wiffen 2007), and especially beneficial for patients who have a comorbidity of depression. They act via histaminic, muscarinic and serotoninergic receptors both peripherally and centrally. However, one should note that the possibility of cardiac toxicity hinders its administration in patients with pre-existing cardiac conditions, especially arrhythmias; they should also be avoided in patients who have suicide risk or poor impulse control (Serpell et al, 2008). A large, retrospective cohort study reported that there was an increased risk to sudden cardiac death at dosages higher than 100mg/day (Ray et al, 2004). Because the recommended dose of TCA can range from 25mg at the starting dose to 150mg/day as the maximum dose (Dworkin et al, 2007), administ ering TCA should be a cautious exercise. In general, TCAs should be started at low dosages, administered at night to minimize sedative effects, and titrated up slowly to be continued for 6-8 weeks to allow analgesic effects (OConnor Dworkin, 2009). SSRNIs SSNRIs such as duloxetine and venlafaxin are less effective than TCAs, but have a better safety profile. Duloxetine has consistently demonstrated efficiency in treating painful diabetic peripheral neuropathy (Dworkin et al, 2007), although its effects in other types of neuropathic pain have not been studies extensively, therefore its efficacy in those types of pain are still uncertain. Calcium channel ligands Calcium channel ligands, e.g. gabapentin and pregabalin, bind to the voltage-gated calcium channels at the ÃŽÂ ±2- Ã‚ ¤ subunit to modulate neurotransmitter release from presynaptic nerve terminals (Figure 7). Both drugs have been shown to be efficacious South Africa: Language and Culture South Africa: Language and Culture What is South African Culture? South Africa is known as the rainbow nation as it has complex and diverse cultures. (South African Languages and Cultures. It is a melting pot of culture; here are a few cultural aspects to admire about South Africa: Mapungubwe, Limpopo Province, is one of the richest archaeological sites in Africa. Two globally important battles namely, The Anglo Boer War and the Anglo Zulu War were both fought on South African soil. Since the freedom from Apartheid, dance has become a prime means of artistic expression. The Magaliesberg mountain range is said to be the oldest mountain range on earth. The Drakensberg mountain range runs the length of the country and is a Unesco World Heritage site. The Vredefort Dome is the oldest and largest visible meteorite impact site in the world. South Africa has a celebration for every event, place, art form, food, drink and agricultural commodity. South Africa has a wide variety of arts and crafts, as well as a wide range of craftwork styles; tribal designs, Afro-French wirework, wood carvings, world-class pottery and bronze casting, stained glass, basket weaving, clay and stone sculpting, dung paper and waste ornaments. The Drakensberg mountain range is the worlds largest art gallery and is a monument to the San Bushmen. Jukskei, a game which involves a player throwing a wooden pin at a peg in the ground. It has been identified as one of the seven indigenous games that should be encouraged and developed. After the Apartheid era, the youth of South Africa started to find their own voice in a style of music called Kwaito. Nguni cattle, they are indigenous to South Africa and might possibly be the most beautiful cattle in the world with their variously patterned and multicoloured hides. The Owl House, Nieu Bethesda, is a fascinating world of sculptures made from concrete and glass. The Cradle of Humankind has one of the worlds richest concentrations of hominid fossils. The Quagga, was extinct but has been rebred. It is a zebra-like animal but only has stripes on the front half of its body. Mark Shuttleworth was the first African in space. South Africa is home to seven Unesco World Heritage sites. South African cultural villages allow visitor to experience firsthand the cultures and traditions of our country, including food, drink and accommodation. South Africa produces 3.1% of the worlds wine and ranks number nine in overall volume production. The above text was referenced from: The A to Z of South African Culture 2010:1 During the Apartheid era, the government divided this diverse country into four population groups, namely white, black, coloured and Asian. (South African culture is impossible to capture in a nutshell, as the country is home to a rich variety of cultural groups of diverse ethnic and national origins. [sa]) These population groups were grouped as follows: White: English, Afrikaans, Jewish, Portuguese, Greek and Lebanese. Black: tribal groups, namely Xhosa, Zulu, Ndebele, Swazi, Tswana and Sotho. Coloured: people of mixed origin, mainly Afrikaans speaking and also a lot closer to the white cultural trends. Asian: people of Indian decent. The above text was referenced from: South African culture is impossible to capture in a nutshell, as the country is home to a rich variety of cultural groups of diverse ethnic and national origins. [sa] South Africa has eleven official languages, namely English, Afrikaans, Tsonga, Zulu, Tswana, Xhosa, Venda, Swazi, Southern Sotho, Ndebele and Sepedi. (South African Languages and Cultures [sa]) South Africas language distribution is as follows: Figure: Language distribution chart (South Africa Info) Xhosa Language: The word Xhosa is derived from the Khoisan language, which means angry men. South African Languages and Cultures [sa] There are about eighteen percent of Xhosa speaking people in South Africa, and are mainly found in the Eastern Cape. (South African Languages and Cultures [sa]) This makes Xhosa the second most spoken language in South Africa. (Languages of South Africa 2010:1) There are nine Xhosa speaking groups, some chiefdoms are larger than others, but there is conformity among them, the conformity can be seen in the homestead layouts. (Magubane 1998:10) Culture: The Xhosa speaking people were one of the first chiefdoms to be exposed to European explorers, hunters, traders, missionaries, soldiers and colonial administrators. (Magubane 1998:12) This exposure therefore altered the culture of the Xhosa people. Xhosa marriage is a polygynous affair as the chiefs and wealthy men, who had lots of cattle married more than one woman and in some instanced has as many as four wives. (Magubane 1998:20) These wives were distinguished in rank according to different houses. (Magubane 1998:20) The Great Wife was responsible in bearing a son, and of course heir who would eventually take over his fathers possessions, i.e. cattle. (Magubane 1998:24) Labola is a big part of the Xhosa culture, labola also meant that different groups could forge alliances as marriage within a clan is prohibited. (Magubane 1998:28) In a modern day Xhosa marriage negotiation it is common that money instead of cattle will be accepted. (Magubane 1998:25) Traditional rituals are performed throughout the life-cycle of the Xhosa people, from birth to puberty, marriage to menopause and filly to death. (Magubane 1998:32) One of these rituals is that of male initiation through circumcision. This ritual came about as men had to be circumcised to become a warrior, and had to be a warrior before he could marry. (Magubane 1998:33) Architecture: Dwellings consisted of a circular frame of poles and saplings, which were bent and bound in the shape of a beehive and thatched from top to bottom with grass. (Magubane 1998:18) this structure was then plastered with a mixture of mud and dug to provide adequate insulation. (Magubane 1998:18) screened off cooking areas, had an earthen oven for baking. (Magubane 1998:18) Zulu Language: Zulu people form the largest ethnic group in South Africa (Languages of South Africa 2010:1) and therefore Zulu is one of the most spoken languages in South Africa and is also understood by half of the South African inhabitants. (South African Languages and Cultures [sa]) South African English has adapted and was also inspired by many of the Zulu words, and therefore incorporate it into the English language. (South African Languages and Cultures [sa]) Culture: The Zulu nation arose in the 16th century; the Zulu warrior Shaka raised the nation to prominence in the 19th century. (Languages of South Africa 2010:1) The classic novel Chaka, by Thomas Mofolo, reinvents king Shaka into a heroic figure. (Languages of South Africa 2010:1) The current monarch is King Goodwill Zwelithini. (Languages of South Africa 2010:1) the present kings powers are essentially symboliche carries a sacred axe on important state occasions and he presides over key rituals, (Magubane 1998:37) Zulu children are exposed to nature at an early age which encompasses a deep understanding and empathy for the environment they live in. (Magubane 1998:45) Traditional foods include amasi (curds of milk) which is eaten either with maize meal or vegetables. Maize meal is either boiled into a thick porridge or eaten with vegetables. Meat was only eaten on special occasions, such as a wedding. (Magubane 1998:47) The Zulus are very crafty. The women are responsible for mat-making, beadwork and pottery. The men do woodwork and specialise in spoons, meat trays and milk pails which are crafted out of one piece of wood. (Magubane 1998:47) Traditional medicines in the Zulu culture are ancient, these medicines are divided into two parts, the Traditional Herbalist who administers medicine made from plants and animals, and the Diviner who smells out the complaints using bones, shells, seeds or other artefacts. (Magubane 1998:61) A category in the Diviners is the isangoma, who is a medium that makes contact with the ancestral spirits and prescribes medicine according to their dictates. (Magubane 1998:62) Music, song and dance have always been important in Zulu culture as it helps maintain a sense of group solidity especially in times of strees, joy and change. (Magubane 1998:62) The Zulu society had many stringed instruments, such as the uGubu which stringed bow with a calabash attached to the end. (Magubane 1998:62) Architecture: The extended homestead was roughly circular in form and was build on sloping ground facing east wherever possible, with the slope falling away to the main entrance, so that the chief dwelling would be on the highest ground. (Magubane 1998:40) In the centre of this homestead would be the cattle byre which is also linked to the temple, which is where traditional rituals would take place. (Magubane 1998:40) The building of these dwellings were the mens job and would often be a social event where the women would brew beer and neighbours, even passers-by, would come and lend a hand in erecting these dwellings. (Magubane 1998:43) The dwellings were either beehive or dome shaped. Saplings would be embedded into a circular dug trench; the saplings were then bent over and tied down to create framework which would then be tightly thatched. (Magubane 1998:43) There were no windows but the door was very low, people had to entre on their hands and knees. This door was then closed at night by means of a wicker door that was fastened with a cross-stick. (Magubane 1998:43) Afrikaans Language: Afrikaans is spoken by a majority of South Africans, either as a first or second language. Afrikaans is a rich cultural languages with much heritage from the Dutch, Afrikaans even means Africa in Dutch. (South African Languages and Cultures [sa]) Afrikaans is mainly spoken by white Afrikaners, coloured South Africans and a section of the black population. (Languages of South Africa 2010:1) Venda Language: Venda is also known as Luvenda or Tshivenda and is mostly spoken in the Northern parts of South Africa. (South African Languages and Cultures [sa]) The people who speak Venda have a Royal Family and show women great respect, therefore women are allowed to become Queens and Chiefs of their own tribes (South African Languages and Cultures [sa]) Culture: For a Venda person, music is one of the most important aspects to their culture, especially drum beats. (South African Languages and Cultures [sa]) They are hard working people but after working all day on a field, there is always music, a few drinks and dancing. (South African Languages and Cultures [sa]) A drum, named Ngoma Lungundu, is the centural feature in Venda culture. (Magubane 1998:82) Status and power are expressed through music, dance, and song. (Magubane 1998:87) Venda people use many musical instruments, even instruments that have vanished from other cultures in Africa; they use xylophones, thumb pianos, reed flutes, and three different types of drums. (Magubane 1998:87) The Venda pottery style was established in the 14th and 15th Century. (Magubane 1998:82) The young Venda men and old Venda men were highly regarded, as the Venda people believe that the young men are still close to the ancestors, while the old men are about to rejoin the ancestors. (Magubane 1998:84) Initiation played a big role in Venda culture, as with most South African cultures. (Magubane 1998:84) Initiation ceremonies were held for the many stages in life and would be made possible through external forces such as the ancestors, good and bad spirits, as well as witches. (Magubane 1998:84) A python, in Venda culture, is associated with fertility and the movements of a baby in the womb. (Magubane 1998:87) Venda women were held in much regard, unlike most African women. (Magubane 1998:89) venda women were in absolute control if in her courtyard, and elderly women played an important role in Venda society by telling the children traditional stories. (Magubane 1998:89) Venda women are able to own property and can become ruler of a clan if there was no male heir. (Magubane 1998:89) Architecture: Traditional Venda villages are surrounded by stone walls, which can still be seen near/under cliffs. (Magubane 1998:84) These villages are laid out so that the King is on the highest part of the land, with his wives and children around him, who are then surrounded by the rest of the inhabitants, who will protect the King and his family if there were to be a threat. (Magubane 1998:84) Ndebele Language: Ndebele language is split into two chief dialects namely, Southern Ndebele and Northern Ndebele, but the more common spoken dialect is Southern Ndebele. (South African Languages and Cultures [sa]) Ndebele is only spoken at home, and therefore only moves through generations, therefore it is thought to be a vanishing language. (South African Languages and Cultures [sa]) Culture: To tourists, the Ndebele culture is best known for their vibrant geometric patterns which decorate their houses, clothes and can also be seen in their beadwork. (Languages of South Africa 2010:1) These vibrant patterns embrace a variety of forms and symbols, such as natural objects, geometric forms and now days letters of the alphabet, numbers, representations of urban buildins, windmills and aeroplanes. (Magubane 1998:76) Ndebele life is characterized, life many other African groups, by the spirit world. (Magubane 1998:67) The spirit world is made up of the Ndebele ancestors who require constant sacrificing to keep them placid. (Magubane 1998:67) The Ndebele society is patriarchal; this was intensified by the white farmers who looked to Ndebele family labour where the men had to work for the white farmer. (Magubane 1998:70) The Ndebele man then moved away from the white farms and started their own businesses as taxi drivers or builders. (Magubane 1998:70) The Ndebele women would work as domestic servants in Pretoria but always returned home to look after the children and set up the homestead. (Magubane 1998:70) While the women were at the homestead, they would be supported by their husbands as well as making and selling beadwork, mats and dolls. (Magubane 1998:70) There is much deliberation on if the adornments worn by the Ndebele women are strictly for their own sensuality or whether their husbands want their wealth to be shown on their wives. (Magubane 1998:76) The most popular adornemnts worn by Ndebele women are the beaded wire hoops and/or copper or brass rings that they wear around their necks, arms, legs and stomach. (Magubane 1998:77) Sepedi Language: Sepedi is also known as Sesotho or Northern Sotho. (South African Languages and Cultures [sa]) But this language is best known for their wedding ceremonies. (South African Languages and Cultures [sa]) Culture: In the Sepedi culture, it is well known that the brides father ask the groom for lebola. Lebola is item/s exchanged for their daughter, for example money or livestock. (South African Languages and Cultures [sa]) The wedding is held at the brides or grooms home, but before the ceremony, the bride (dressed in a cows hide dress) has to go down to the river and collect water and wood for the ceremony. (South African Languages and Cultures [sa]) Once the ceremony is done, a sheep is then slaughtered in the back yard and the meat is equally divided between both families. (South African Languages and Cultures [sa]) Setswana Language: Setswana is commonly known as Tswana, which is related to the other Sotho languages. (South African Languages and Cultures [sa]) Setswana was mostly spoken in Botswana, but migrated into North Western South Africa. (Languages of South Africa 2010:1) Dr. Robert Moffat built the first school in Botswana and realised that he needed to use and write Setswana in his teachings, therefore Setswana was the first Sotho language to be in a written format. (Languages of South Africa 2010:1) Culture: Setswana is part of the Sotho-Tswana division, which use totems to contact their ancestors and these totems symbolise the sacred creature which is not to be hunted, the Setswana totem is a fish. (Magubane 1998:11) In the Setswana culture, wealth is measured by how many cattle they have in their possession; this is then ranked and put into a document called the Setswana Forbes, which lists all the names of the wealthy Setswana people. (South African Languages and Cultures [sa]) Setswana culture is also widely known for their Traditional healers, or sangomas, which play an important role in their culture. (South African Languages and Cultures [sa]) Southern Sesotho Language: Southern Sotho is spoken by more than five million South African inhabitants. (South African Languages and Cultures [sa]) It is a very complicated language, but once you get to understand it, it is a beautiful language. (South African Languages and Cultures [sa]) Sesotho originally was spoken in Lesotho, but moved into South Africa. It was also one of the first African languages, along with Setswana and Zulu, to be put into a written form as well as into literature. (Languages of South Africa 2010:1) Culture: Southern Sotho is part of the Sotho-Tswana division, which use totems to contact their ancestors and these totems symbolise the sacred creature which is not to be hunted, the Southern Sotho totem is a crocodile. (Magubane 1998:10-11) The Southern Sotho culture is one that believes strongly that Children benefit from serving their elders. (South African Languages and Cultures [sa]) Marriages are more often than not pre-arranged but in todays day and age, this has become less of normality as they are now able to pick their life partners. (South African Languages and Cultures [sa]) Swati Language: The Swati language is also known as the Swazi language. (South African Languages and Cultures [sa]) It is a very similar language to the Ndebele, Xhosa and Zulu language, and often gets confused with these languages. (South African Languages and Cultures [sa]) The language and culture of the Swati was highly influenced by the Zulus. (South African Languages and Cultures [sa]) Culture: The Swatis have many traditional events and the culture is one of colourful outfits with red feathers, carrying shields and wearing multicoloured necklaces. (South African Languages and Cultures [sa]) The Reed dance festival is one of their great festivals. (South African Languages and Cultures [sa]) The ceremony is held for eight days which runs through the end of August till the beginning of September. (South African Languages and Cultures [sa]) This ceremony is for all unmarried women and is to protect the womens chastity (South African Languages and Cultures [sa]) Tsonga Language: The Tsonga language is spoken throughout southern Africa. (South African Languages and Cultures [sa]) Tsonga is a language that does not use the English alphabet, but instead the Latin alphabet. (South African Languages and Cultures [sa]) Therefore it is a difficult language to learn or understand. Culture: The first Tsonga speaking people were traders of cloth and beads for ivory, copper and salt that was eventually joined by co-linguists pushed from the coast by Nguni raiders. Magubane 1998:90 The birth of a child is a great time for all Tsonga speaking people. (Magubane 1998:95) Babies are doctored with medicines and decorated with charms and beaded bangles. Magubane 1998:95 A Tsonga marriage is not just a relationship of two individuals, but an agreement and new relationship between the two families. (Magubane 1998:96) There is a sacrifice before the bride leaves her family and her ancestors to join her new family, her new family will now take her in as one of them and she will have to learn their etiquette and rules of behaviour. (Magubane 1998:96) Most of the agricultural work was done by women, but the harvesting was done in collaboration with the surrounding communities, with the owner/host of the land providing beer and refreshments therefore making it a festive occasion. (Magubane 1998:98) Venison was a vital part in Tsonga diet, so was fish as fishing was an important community activity. (Magubane 1998:98) Tsonga men have through the ages started working in the South African mines and send money home to their families. (Magubane 1998:99) They have to spend copious amounts of time on busses and trains, and have to live in hostels near to the mining towns. (Magubane 1998:99) The Tsonga people are able to play wind, stringed and percussion instruments, the string instruments being the most important. (Magubane 1998:99) The two other instruments they are able to play, but fall out of the mentioned catagories is the hand piano and the xylophone. (Magubane 1998:99) The stringed instruments they are able to play: Vibrating Bow Stringed bow attached to a calabash Hollow reed bow Wire stringed bow with a thickened handle plucked with a flat piece of wire The above text was reference from: (Magubane 1998:99) The wind instruments they are able to play: Cross flute Shepherds pipe Antelope horn trumpet The above text was reference from: (Magubane 1998:99) The percussion instruments they are able to play: Tambourines Drums The above text was referenced from: (Magubane 1998:99) Architecture: A Tsonga homestead comprises of the man, his wife/wives, their children and their sons families. (Magubane 1998:94) The houses are cylindrical with earthen walls and conical thatched or reed roofs. Magubane 1998:94 The homestead is generally circular with a central cattle byre and a main entrance on the eastern side, there may also be sub-entrances on the side of the water and fields. (Magubane 1998:94) English Language: South African English is rich and peculiar as it is influenced by most of the other ten languages. (Languages of South Africa 2010:1) For example: ..cars stop at robots, not traffic lights. A pickup truck is a bakkie, sneakers are takkies, a hangover is a babbelas, (Languages of South Africa 2010:1) English is understood across South Africa and is generally the chosen language in business, politics and media. (Languages of South Africa 2010:1) English is only spoken by 10% of South Africans, but is the primary language tought at primary, secondary and tertiary educational centres. (Languages of South Africa 2010:1) What artefacts are unique to each culture? Archaeology is important as it is able to tell us when and where people settled and how they lived. Archaeology is also able to link different cultural groups through the artefacts they leave behind. (Magubane 1998:8) Archaeological time periods and artefacts found from each period: Early Stone Age stone artefacts such as hand axes and cleavers. Middle Stone Age stone artefacts such as points and scrapers, as well as grindstones. Later Stone Age new technologies made way for the bow and arrow, and traps and snares. Early Iron Age new technology made way for hoes, axes, decorative pots and bowls, ornate metal work and complex terracotta sculptures. The above text was referenced from: Magubane 1998:8 The Bantu-speaking people have been thought to emerge from the Iron Age communities; the bantu-speaking people are divided into two groups, the Nguni speaking and the Sotho-Tswana speaking people. (Magubane 1998:10) These two groups are linguistically and culturally distinct (Magubane 1998:10) What is a Boutique Hotel? There are a number of characteristics and attributes that constitute a Boutique Hotel. Firstly a Boutique hotel is much smaller than a chain-hotel as the maximum amount of rooms a Boutique Hotel has is one-hundred. (Nobles Thompson 2001:1) Atmosphere is very important in a Boutique Hotel as it creates a memorable experience. (Nobles Thompson 2001:1) Management and staff need to anticipate guests needs and wants, knowing what a guest wants, when they want it and how they want it. (Nobles Thompson 2001:1) Unique and interesting themes, design and architecture. (What is a Boutique Hotel? 2003 2010) Stylish appearance (What is a Boutique Hotel? 2003 2010) Equally appropriate for business, honeymoon or vacation. (What is a Boutique Hotel? 2003 2010) Target market for Boutique Hotels is 25 55 age range and middle to upper income level. (What is a Boutique Hotel? 2003 2010) Boutique hotels offer a completely unique experience. Boutique Hotels can be hip and happening or historic in theme. (What is a Boutique Hotel? 2003 2010) Boutique Hotels offer comforts, such as bathrobes and fireplaces; spa-like services, such as healthy food choices, mind and body cleansing; the latest technology, as well as on-site dining, bar and lounge areas that are open to the public. (What is a Boutique Hotel? 2003 2010) How do you reuse an old building to create a new exciting interior? By preserving historic buildings and by updating the building and its interior for a new use (Bijelic 2006:1), the population and generations to come will be able to understand and appreciate South African heritage and culture. (The WBDG Historic Preservation Subcommittee 2010:1) By reusing existing buildings and transforming them into a new purpose, the architects and designers are in essence being environmentally responsible. (The WBDG Historic Preservation Subcommittee 2010:1) Existing buildings are in essence energy efficient as they already exist and therefore there is no need to create new building materials, which leave a carbon footprint behind. (The WBDG Historic Preservation Subcommittee 2010:1) Minor modification to the exterior or interior of these historical/existing buildings are possible and plausible as this will then create a new use for these buildings as well as upgrade these buildings in order to meet the modern building requirements and codes. (The WBDG Historic Preservation Subcommittee 2010:1) Converting historical buildings to meet modern demands might be a challenge, but there are advantages as clients will eventually realise the potential financial, cultural and marketing advantages of preserving architectural history. (Bijelic 2006:1) Practical benefits of preserving existing/historical buildings: Preservation of the history and authenticity. Increases the commercial value of the building and its ornaments/material which are more often than not high quality and not affordable. Sustainable building practice as there is less construction and demolition, and less need for new building materials as the existing infrastructure will be used. Energy efficient as there will be no energy waste on demolition and new construction. The above text was referenced from: The WBDG Historic Preservation Subcommittee 2010:1 Identify, Investigate, Develop, Execute and Educate are the five basic steps of preserving a historical building. (The WBDG Historic Preservation Subcommittee 2010:1) The four treatment approaches for historic buildings are: Preservation maintenance, stabilisation and repair of existing historic materials. Rehabilitation to alter or add to historic property. Restoration depicting the property at a particular period of time while erasing the evidence of other eras. Reconstruction re-creates non-surviving parts of the property. The above text was referenced from: The WBDG Historic Preservation Subcommittee 2010:1 Before preserving or reusing an existing building, the architect and/or designer needs to make sure that the original function of the building and the proposed new function of the building coincide and/or are compatible in order to reduce the deconstruction of the historic materials and ornaments. (The WBDG Historic Preservation Subcommittee 2010:1) In order to maintain the integrity of the historical building, the following preservation design goals need to be implemented: Update building systems this requires striking a balance between original building features and accommodating the new technologies and equipment. Life safety and security needs accommodate new functions, changes in technology and improved standards of protection. Comply with accessibility requirements provide access for persons with disabilities while meeting preservation goals. The above text was referenced from: The WBDG Historic Preservation Subcommittee 2010:1 Relevant Codes and Standards Previous research that has been done on the topic Field Research Data capturing I have sent out questionnaires to a number of architectural firms and travel agencies, as well as the Department of Tourism, Department of Home Affairs, The City Council of Johannesburg and the City Council of Tshwane. Explain in detail who, what, where, how and why The above mentioned parties will be able to advise me on (1) if there is a need for Boutique hotels in South Africa and (2) how to go about reusing/renovating existing buildings in order to preserve the environment as well as create a new, fresh Boutique hotel with the correct regulations.