Neuropathic pain is defined as "pain initiated or caused by a primary lesion or dysfunction in the nervous system". In contrast to physiological pain that warns of noxious stimuli likely to result in tissue damage, neuropathic pain serves no protective function. Examples of neuropathic pain states include postherpetic neuralgia (shingles) and phantom limb / stump pain. This pain state also exists in the orofacial region, with the possibility of several variants including atypical odontalgia and burning mouth syndrome. There is a paucity of information on the prevalence of neuropathic pain in the orofacial region. One study assessed patients following endodontic treatment and found that approximately 3 to 6percent of patients reported persistent pain. Patients predisposed to the condition atypical odontalgia (phantom tooth pain) include those suffering from recurrent cluster or migraine headaches. Biochemical and neurobiological processes leading to a neuropathic pain state are complex and involve peripheral sensitisation, and neuronal plasticity of the central and peripheral nervous systems. Subsequent associated pathophysiology includes regional muscle spasm, sympathetic hyperfunction, and centralisation of pain. The relevant clinical features of neuropathic pain are: (i) precipitating factors such as trauma or disease (infection), (ii) pain that is frequently described as having burning, paroxysmal, and lancinating or sharp qualities, and (iii) physical examination may indicate hyperalgesia, allodynia and sympathetic hyperfunction. The typical patient complains of persistent, severe pain, yet there are no clearly identifiable clinical or radiographic abnormalities. Often, due to the chronicity of the problem, afflicted patients exhibit significant distress and are poor pain historians, thus complicating the clinician's task of obtaining a detailed and relevant clinical and psychosocial history. An appropriate analgetic blockade test for intraoral sites of neuropathic pain is mucosal application of topical anaesthetics. Other, more specific, tests include placebo controlled lignocaine infusions for assessing neuropathic pain, and placebo controlled phentolamine infusions for sympathetically maintained pain. The treatment and management of neuropathic pain is multidisciplinary. Medication rationalisation utilises first-line antineuropathic drugs including tricyclic antidepressants, and possibly an anticonvulsant. Topical applications of capsaicin to the gingivae and oral mucosa are a simple and effective treatment. Neuropathic pain responds poorly to opioid medication. Psychological assessment is often crucial in developing strategies for pain management. Psychological variables include distress, depression, expectations of treatment, motivation to improve, and background environmental factors. To enable a greater understanding of neuropathic pain, thereby leading to improved treatments, high-performance liquid chromatography-mass spectrometry is one analytical technique that has the potential to contribute to our knowledge base. This technique allows drugs and endogenous substances to be assayed from one sample in a relatively short time. The technique can identify, confirm, and measure the concentrations of multiple analytes from a single sample.

For pain research, the orofacial region is unique in a number of ways. The region has complex local anatomy, including substantial sensory innervation from neural pathways, and muscles of facial expression that convey important information concerning pain intensity and associated psychological traits. Although chronic orofacial pain conditions appear prevalent, useful documentation on pain intensity ratings using well established instruments is sparse. In particular, two conditions, atypical facial pain and atypical odontalgia, are poorly understood in aetiology so that definitive treatment modalities are severely limited. The region's local biofluid, saliva, has been used to diagnose various local and systemic disease states, and to quantitate drug concentrations. However, recent studies indicate that saliva also contains some of the same peptides, e.g. bradykinin, that are involved in pain mechanisms. It may be that pharmacological-pharmacokinetic studies of these peptides could shed more information on thesignificance of their presence in saliva. This thesis consists of four major sections. Section 1 comprises of three clinical studies investigating orofacial pain. Section 2 deals with clinical laboratory studies of saliva. Section 3 is concerned with the development of chromatographic methods to assay bradykinin and its pharmacokinetics in saliva. Section 4 uses chromatography for the identification of novel salivary peptides. This thesis, then, presents clinical studies of orofacial pain and pharmacological investigations of saliva as the local biofluid.

Thesis (Ph. D.)--Pennsylvania State University, 1968. / Includes bibliographical references.

Graduation date: 1999

The separating characteristics of high performance liquid chromatography (HPLC) columns, measured in terms of the height equivalent of a theoretical plate (HETP) and skewness of the eluted peak, are investigated using computational fluid dynamics (CFD). Gradually expanding and contracting sections are introduced at the inlet and outlet, respectively, in columns with and without frits and their performance was compared with that of the conventional columns without expanding and contracting regions. / Singapore-MIT Alliance (SMA)

Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2007.

Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: Abraham M. Lenhoff, Dept. of Chemical Engineering. Includes bibliographical references.

Acid/base modifiers are sometimes used as additives in the elution on columns packed with amylose tris(3,5-dimethylphenylcarbamate) stationary phase to separate enantiomers. When modifiers are removed from the mobile phase, the stationary phase is affected in ways that are not understood because of the lack of systematic studies, making the scale-up of preparative separations difficult to predict. Once a column has been exposed to these modifiers, the selectivity of certain pairs of enantiomers may change, for the better or the worse. Numerous pairs of molecules affected by this phenomenon are listed in the literature. Five pairs of these molecules were chosen, the selectivity of which changes after an acidic or basic solutions has been percolated through the column. The selectivity of the ketoprofen, 4-chlorophenylalanine methyl and ethyl esters improves after a solution of ethanesulfonic acid is percolated through the column. The selectivity of the propranolol HCl and Troger’s base increases after a solution of diiospropylethylamine is percolated through the column. The selectivity of these the 4-chlorophenylalanine ethyl ester, propranolol and Troger's base enantiomers are inversely affected by percolation of the opposite acid/base solution. This residual change in certain enantiomeric separations has been named the Memory Effect. In contrast, trans-stilbene oxide (TSO) was used as a standard to determine the column's stability because no Memory Effect is observed for this separation (the retention, enantioselectivity, and resolution remain constant). Karl Fischer titrations showed that only slight changes in the mobile phase's water content occurred, and that the water to polymer repeat unit ratio is important. Analytical studies of the stationary phase suggest that slow protonation/deprotonation of water bounded to the carbamate moiety may be responsible for the Memory Effect. It has been shown that the Memory Effect can be minimized by percolating through the column a sufficiently concentrated solution of the appropriate acid or base. Thus, columns that were unreliable for method development, due to the Memory Effect, can now be used. As a result, the scale-up of separations can be predicted and successfully performed. Finally, a test was devised to determine if a column was under the influence of the Memory Effect.

Thesis (M. Sc.)(Chemistry)--University of Pretoria, 2005. / Includes summaries in English and Afrikaans. Includes bibliographical references. Available on the Internet via the World Wide Web.

This thesis details various techniques and considerations for the purification of complex biomacromolecules.   Initially an α-mannosidase from babaco fruit was purified using anion exchange-, lectin affinity- and size exclusion chromatography.  The enzyme was approximately 260-280 kDa in size with an apparent an unusual octagonal stoichiometry and displayed properties similar to other known plant α-mannosidases.   Mucins were fractionated by ion exchange and size exclusion chromatography to assess the properties that govern the mucin surface coating interactions in biomaterial research.  Commercially available mucins, of bovine and porcine origin, as wells as crude human mucin were tested. All showed to consist of a population of molecules which differ in size, charge and composition.   The third part of the thesis concerns different aspects of plasmid DNA purification processes. A two-step method for analysis of plasmid DNA consisting of size exclusion followed by thiophilic adsorption chromatography was evaluated. It allowed determination of the supercoiled plasmid DNA concentration in all process steps without requirement for extensive sample preparation. This method was shown to be fully comparable in terms of accuracy to capillary gel electrophoresis, considered as the industry standard. Purification of plasmid DNA generally involves bacterial cell alkaline lysis, which creates a solution with flocculate material which needs to be removed prior to further processing. The addition of ammonium hydrogen carbonate to the suspension was evaluated to clarify the solution. The released carbon dioxide and ammonium lifts the flocculate to the surface and allows draining of a clear solution. The method is fully scalable, does not affect the plasmid DNA quality and requires no special equipment. Thiophilic adsorption chromatography was evaluated for simplification of an existing commercial large scale purification process and was shown to increase both product purity and yields of several tested plasmids. Also, implementation of this step significantly reduced overall production process time.