Approximately two-thirds of patients will experience pain following spinal cord injury (SCI). This pain can arise as an immediate consequence of SCI, or can develop over time into chronic, neuropathic pain. Individuals are frequently prescribed opioid analgesics, including morphine, for the treatment of pain in both the acute and chronic phases of SCI. Yet, despite the prevalence of opioid use, no studies have examined the addictive potential of opioids, or their secondary effects, following spinal injury. These experiments used a clinically relevant self-administration paradigm to examine both addiction and functional recovery after morphine administration. To assess morphine administration in the acute phase of SCI, animals were placed in operant chambers 24-hours following spinal injury. In the chambers, depression of a reinforced lever resulted in an intravenous infusion of morphine (or vehicle). Animals were placed in the chambers for 7, 12-hour sessions and could administer up to 30 mg of morphine per session. Morphine self-administration was also examined in the chronic phase of injury. Animals were placed into operant chambers for 7, 12-hour sessions beginning 14 or 35 days after injury. The amount of morphine administered, as well as recovery of locomotor function and general health, was compared across subjects with SCI and sham (no injury) controls. In the acute phase of injury, SCI significantly reduced self-administration of morphine, but administration led to decreased recovery of locomotor function and weight loss. In the chronic phase of injury, self-administration did not differ between contused and sham animals. All subjects administered the full amount of morphine available each day. In this phase of injury, morphine administration led to significant weight loss, but did not attenuate recovery of locomotor function. These studies suggest that spinal injury reduced the addictive potential of morphine in the acute, but not the chronic, phase of SCI. However, acute administration of high doses of morphine decreased recovery of locomotor function. Morphine should not be used in this phase of injury for the clinical treatment of pain. In the chronic phase, opioid use must be closely monitored as use may result in addictive behavior.

Altered sexual function is one of the most devastating consequences of spinal cord trauma (SCT). Despite this fact, current knowledge of the neural circuitry regulating sexual response in the spinal cord (SC) in healthy humans is remarkably incomplete. In order to better understand the changes that occur to sexual responses following SCT, we must elucidate the neural transmission of sexual function in healthy humans. Functional magnetic resonance imaging (fMRI) techniques to map neuronal function have been adapted for the SC and can now reveal this neural circuitry. We mapped, with spinal fMRI, neuronal activity in the lower thoracic, lumbar and sacral SC in healthy men (n = 10) and women (n = 9) that occurs in response to intermittent audiovisual stimulation (AVS), intermittent genital self-stimulation (GSS) and the combination of the former and latter, applied continuously and simultaneously until orgasm (AVGSS). MR images revealed predominantly increased signal intensity changes (ΔS+) in the autonomic preganglionic nuclei of the lower thoracic, lumbar and sacral SC in women and mostly decreased signal intensity changes (ΔS-) in comparable regions in men. In functional MR images, ΔS+ are related to increased neuronal input while ΔS- are associated with diminished neuronal input to a particular region. Linear regression analyses uncovered a greater number of inverse correlations between SC ΔS and scores of sexual function in women than in men indicating greater descending modulation of SC circuits regulating sexual responses in women than in men. Taken together, our results demonstrate that spinal fMRI is an effective and sensitive technique that can reveal signal intensity changes in the lower thoracic, lumbar and sacral SC associated with AVS, GSS and AVGSS in healthy men and women. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2009-10-06 21:26:15.011

No description available.

The androgen receptor (AR) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. Mutations in the androgen receptor are associated with androgen insensitivity syndrome (AIS), and a neurodegenerative disease, spinal bulbar muscular atrophy (SBMA). Most of the mutations causing AIS are loss-of-function missense mutations whereas SBMA is caused by a gain-of-function polyglutamine expansion in the N-terminal domain of the protein. Characterization of AR mutations has led to a better understanding of structure-function relationships of the AR and serves as a prototype for steroid receptors mechanisms of action. / In the first paper, we examine the role of an AR mutation in causing mild androgen insensitivity syndrome. We found that this mutation conferred reduced transactivation by AR through impaired interactions with the AR coactivator, TIF2, and impaired homodimerization. / In the second paper, we investigate the role of the AR polyGln expansion mutation in SBMA pathogenesis. Recent evidence has implicated proteolytic degradation of polyGln-expanded proteins and their subsequent intracellular aggregation in polyGn-expanded disease pathogenesis. We examined the role and composition of aggregates using fluorescently-tagged AR and found that proteolysis need not be a prerequisite for aggregation and that aggregation is not necessary for poly-Gln-induced cellular toxicity. / Finally, we characterize the novel heterodimerization of AR and ERalpha. We determined that this direct interaction has functional implications for the transactivational properties of both receptors.

Thesis (M.Tech-: Chiropractic)-Dept. of Chiropractic, Durban Institute of Technology, 2005 x, 57 leaves, Annexures 1-10 / To determine if serum cortisol levels are increased following Spinal Manipulation Therapy (SMT) to the low back region and to determine the effect of a short rest interval on the cortisol levels

Thesis (M.Tech.: Chiropractic)-Durban University of Technology, 2008. xviii, 83, [29 ], 25 leaves / Golfing literature today recommends to both the amateur and professional golfers to try and achieve maximum performance with each golf club (Seaman, 1998 and Bulbulian, Ball and Seaman, 2001). This encourages golfers to use a state of maximum spinal rotation in their golf swing in order to achieve optimal performance (Seaman, 1998), thus resulting in back pain becoming endemic in the golfing population. Thus if it is considered that performance, in terms of the golf swing, is mainly influenced by; • the strength and power of the torso, i.e. the low back and abdominal muscles (Chek, 2003), • as well as muscle balance and flexibility, i.e. those muscles which are responsible for the static and dynamic postural stability of the golf swing (Chek, 2003). It then stands to reason that any decrease in the range of motion of the lumbar or thoracic spine of the amateur golfer, in terms of biomechanics, could affect their performance (Nordin and Frankel, 2001). In this regard it is hypothesised that altered biomechanics could be that of asymptomatic segmental joint dysfunction . In terms of interventions Kirkaldy-Willis and Burton (1992) explained the effect of SMT in the treatment of low back pain, similarly Bergmann et al. (1993) and Vernon and Mrozek (2005) further proposed the following effects of spinal manipulative therapy (SMT): • SMT may stretch or break intra-articular adhesions that form from immobilised facet joints due to acute synovial reactions. • SMT allows entrapped menisci to exit the facet joint in which it became entrapped. • If the capsule of the facet gets lodged between two adjacent articular surfaces, the process of SMT could allow this to be freed. • SMT re-aligns misaligned spinal segments to conform to the centre of gravity. It was thus assumed that if these mechanical and reflex mechanisms occur in the symptomatic amateur golfer, they should also occur in the asymptomatic amateur golfer. Currently however very little is known about the effects of spinal manipulative therapy (SMT) on asymptomatic segmental joint dysfunction. Objective: Therefore, the purpose of this study was to evaluate the immediate and short term effect of spinal manipulative therapy (SMT) on asymptomatic amateur golfers in terms of performance indicators. Methods: Forty three asymptomatic participants were randomized to four equal groups consisting of ten participants each (and three drop outs). Three of the groups received a single intervention, i.e. spinal manipulative therapy (SMT) while the last group acted as a placebo control group and received no intervention. Objective measurements were taken using the EDH Sports-FlightScope Pro Electronic Swing Analyser. All objective data collection took place pre and post SMT. Statistical analysis included various statistical methods and correlation analyses, by means of the latest version of SPSS. Results and conclusions: The main findings were that certain outcomes seem to be better with lumbar manipulation alone (smash, horizontal azimuth) and others better with thoracic manipulation alone (CHV, vertical azimuth, distance), but none are better with both lumbar and thoracic manipulation. Therefore in terms of future studies of this nature the treatment groups should be analysed separately and the research powered for such analyses (e.g. larger sample sizes).

Mini-dissertation in partial compliance with the requirements for the Masters Degree in Technology: Chiropractic, in the Department of Chiropractic at the Durban University of Technology, 2009 / The aim of this study was to investigate the relative effectiveness of Transeva and spinal manipulative therapy for mechanical low back pain. The objectives evaluated the effectiveness of only administering Transeva therapy alone, or Spinal manipulative therapy alone as well as Transeva therapy with Spinal manipulative therapy on mechanical low back pain with respect to the patients’ subjective and objective responses to the respective treatment group. The final objective was to correlate the subjective and objective data collected to determine the effectiveness of each of the therapies in comparison with another. Design: A sample of thirty patients diagnosed with mechanical low back pain were accepted into the study. These patients were randomly divided into three groups of 10, which received different treatment protocols for mechanical low back pain. Outcome Measure: The following outcomes were measured; a decrease in pain (measured with the Numerical Pain Rating Scale (NRS), a decrease in disability (measured with the Roland-Morris Questionnaire), a decrease in local tenderness (measured with the pressure Algometer) and an increase in lumbar range of motion (measured with the Inclinometer). The data was collected prior to treatment one, prior to treatment four and at the sixth follow-up visit. Results and Conclusion: All groups improved with the treatments they received; however, no single treatment was statistically better than any other treatment intervention tested. However, the Spinal manipulative therapy group had a statistically significant faster reduction in pain on the NRS readings with p=0.048.

Dissertation submitted in partial compliance with the requirements for the Masterà ¢ s Degree in Technology: Chiropractic, Durban University of Technology, 2008. / Objectives: To determine the short-term effect of an inhaled, short-acting 2-agonist bronchodilator on chest wall expansion (cm) and lung function parameters (FEV1, FVC and FEV1/FVC%) in chronic moderate asthmatics. To determine the short-term effect of spinal manipulation (SMT) and ribcage mobilisation on chest wall expansion (cm) and lung function parameters (FEV1, FVC and FEV1/FVC%) in chronic moderate asthmatics. To determine the short-term effect of a combination of SMT, ribcage mobilisation and an inhaled, short-acting 2-agonist bronchodilator on chest wall expansion (cm) and lung function parameters (FEV1, FVC and FEV1/FVC%) in chronic moderate asthmatics. Methods: Forty-five chronic moderate asthmatics who met all the inclusion criteria of the study were divided into three groups of fifteen each. Group A received a short-acting 2-agonist bronchodilator, Group B received SMT and ribcage mobilisation and Group C received a combination of SMT, ribcage mobilisation and a short-acting 2-agonist bronchodilator. Baseline measurements and testing included chest wall expansion and the lung function parameters FEV1, FVC and FEV1/FVC%. These measurements were repeated 15 minutes post-intervention. Data was analyzed using SPSS version 15.0. Results: There were no statistically significant changes between pre- and post-intervention in the short-acting 2-agonist bronchodilator group with respect to any of the chest wall expansion measurements. There was a statisticallly significant increase in FEV1 between pre- and post-intervention in the short-acting 2-agonist bronchodilator group (p = 0.008). There was a statistically significant increase in the mean pre- and post-intervention axillary chest wall expansion (p = 0.014) as well as the mean of the half-way measurement (p = 0.014) and the overall mean chest wall expansion value (p = 0.001) following SMT and ribcage mobilisation. There were no statistically significant changes in any of the lung function parameter values following SMT and ribcage mobilisation. There was a significant increase for the half-way measurement in chest wall expansion (p = 0.018) in the combination of SMT, ribcage mobilisation and the inhaled, short-acting 2-agonist bronchodilator group. There were no statistically significant changes in any of the lung function parameter values in the combination of SMT, ribcage mobilisation and an inhaled, short-acting 2-agonist bronchodilator. For FEV1, the effect in the short-acting 2-agonist bronchodilator group vs. the SMT and ribcage mobilisation group was statistically significant (p = 0.018). There was no statistical difference in any of the chest wall expansion measurements and FVC and FEV1/FVC% parameters between all three groups. Conclusions The results did not point specifically to one intervention over another for all outcomes. SMT and rib mobilisation had no effect on the lung function parameters, at least in the short term. There was a statisticallly significant increase in FEV1 between pre- and post-intervention in the short-acting 2-agonist bronchodilator group.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban University of Technology, 2008. / To compare trunk flexion and lateral flexion range of motion (ROM) pre-post intervention. To compare the bowling speed of Action Cricket fast bowlers pre-post intervention. To determine the correlation between change in bowling speed immediately post-intervention to change in trunk flexion and lateral flexion ROM immediately post-intervention. To determine the association between change in bowling speed immediately post-intervention and the subjects’ perception of change in bowling speed. Methods: Forty asymptomatic Action Cricket fast bowlers were divided into four groups of ten each. Group 1 received lumbar spine manipulation, Group 2 received thoracic spine manipulation, Group 3 received combined thoracic and lumbar spine manipulation and Group 4 received the sham laser intervention (placebo). Pre- and post-intervention trunk flexion and lateral flexion ROM and bowling speed were measured using a digital inclinometer and a SpeedTracTM Speed Sport Radar. The subjects’ perception of a change in bowling speed post-intervention was also recorded. SPSS version 15.0 was used to analyse the data. Two-tailed tests were used in all cases. Results: Trunk flexion and lateral flexion increased significantly (p < 0.05) post-spinal manipulation. There was a significant increase in bowling speed post-thoracic (p = 0.042) and post-combined manipulation (p < 0.000). A significant yet weak positive correlation (p = 0.003; r = 0.451) was seen in change in bowling speed and change in thoracic flexion and lateral flexion. There was no significant difference in the percentage subjective change by intervention group (p = 0.217). Conclusions: Spinal manipulation is a valid intervention for short-term increase in bowling speed.

The disruption of the survival motor neuron (SMN1) gene leads to the children’s genetic disease spinal muscular atrophy (SMA). SMA is characterized by the degeneration of α-motor neurons and skeletal muscle atrophy. Although SMA is primarily considered a motor neuron disease, the involvement of muscle in its pathophysiology has not been ruled out. To gain a better understanding of the involvement of skeletal muscle pathophysiology in SMA, we have developed three aims: to identify cell-specific Smn-interacting proteins, to characterize postnatal skeletal muscle development in mouse models of SMA, and to assess the functional capacity of muscles from SMA model mice. We have used tandem affinity purification to discover Smn interacting partners in disease relevant cell types. We have identified novel cell-specific Smn interacting proteins of which we have validated myosin regulatory light chain as a muscle-specific Smn associated protein in vivo. We have taken advantage of two different mouse models of SMA, the severe Smn-/-;SMN2 mouse and the less severe Smn2B/- mouse, to study the postnatal development of skeletal muscle. Primary myoblasts from Smn2B/- mice demonstrate delayed myotube fusion and aberrant expression of the myogenic program. In addition, the expression of myogenic proteins was delayed in muscles from severe Smn-/-;SMN2 and less severe Smn2B/- SMA model mice. Muscle denervation and degeneration, however, are not the cause of the aberrant myogenic program. At the functional level, we demonstrate a significant decrease in force production in pre-symptomatic Smn-/-;SMN2 and Smn2B/- mice indicating that muscle weakness is an early event in these mice. Immunoblot analyses from hindlimb skeletal muscle samples revealed aberrant levels of developmentally regulated proteins important for muscle function, which may impact muscle force production in skeletal muscle of SMA model mice. The present study demonstrates early and profound intrinsic muscle weakness and aberrant expression of muscle proteins in mouse models of SMA, thus demonstrating how muscle defects can contribute to the disease phenotype independently of and in addition to that caused by motor neuron pathology.