This thesis describes applications of mathematical modelling to systems of demand analgesia for the relief of acute postoperative pain. It builds upon work described in the D.Phil. thesis of M.P. Reasbeck. Following major surgery, patients are given a hand-held button which they press when in need of pain relief. The relief is afforded by automatic intravenous infusion of opiates. New clinical demand analgesia hardware, PRODAC, has been developed and data have been collected with it in two major trials involving a total of 80 patients. Patients' drug requirements have been found not to be correlated with body weight, contrary to conventional teaching. The type of operation was also found to have no significant influence upon drug requirements. The performance of transcutaneous nerve stimulation (TNS) as a method of analgesia for acute postoperative pain has been studied and found to be poor. Reasbeck's mathematical model of patients in pain has been corrected and extended. The representation of pharmacokinetics has been enhanced by modelling the transfer of drug between blood plasma and analgesic receptor sites as a first-order process. The time constant of this process has been calculated for morphine using a novel method and found to be 12 minutes. On line estimation of 2nd order pharmacokinetic time constants has been found in simulation not to be feasible. New software has been used to tune the revised model to the clinical data collected with PRODAC. Model behaviour is now demonstrably life-like, which was not previously the case. Blood samples taken during demand analgesia have permitted a comparison between measured and estimated drug concentrations, with good results.

This series of experiments examined the neural mechanisms of analgesia caused by local anaesthetic blockade or selective blockade of N-methyl- scD-aspartate (NMDA) receptors at sites in the rat forebrain. Microinjections of the local anaesthetic lidocaine were made into the medial or lateral thalamic nuclei. The results indicate that the medial thalamic nuclei mediate the expression of pain behavior after peripheral injury, whereas the lateral thalamic nuclei influence phasic withdrawal responses, but are not critical for injury-induced pain responses. Electrolytic lesions made in the lateral thalamus verified this latter finding. Intracranial microinjections of the NMDA antagonist AP5 were used to determine if NMDA receptors in the forebrain participate in pain-related central processing. The intralaminar thalamic nuclei, the striatum and the dentate gyrus of the hippocampal formation were indicated as forebrain sites where antagonism of NMDA-sensitive neural mechanisms significantly reduced the expression of pain-related behavior in the formalin test.

No description available.

The mechanisms of pain and hyperalgesia were examined in rats following cutaneous-heat and peripheral-nerve injury. Central mechanisms of hyperalgesia were indicated since a heat injury produced a decrease in foot-withdrawal latencies in the paw contralateral to the injury and an increase in autotomy of the injured paw following section of the sciatic and saphenous nerves. The reduced contralateral foot-withdrawal latencies were reversed by spinal anesthesia and subcutaneous guanethidine, but were unaffected by local anesthetics and capsaicin at the site of injury. The enhancement of autotomy produced by an injury was reduced by spinal anesthesia and a combination of intrathecal capsaicin and subcutaneous guanethidine. Both intrathecal substance P and systemic noradrenaline produced an increase in autotomy following nerve lesions; guanethidine, but neither capsaicin nor procaine, produced a decrease in autotomy. A reduction in inflammation and hyperalgesia within an injured paw was produced by local capsaicin, but not by guanethidine. The results suggest that central mechanisms, such as spinal hyperactivity, combined with peripheral neurogenic mechanisms are involved in the production of hyperalgesia following heat injury. Pain and hyperalgesia following nerve injury are proposed to be due to spinal cord plasticity resulting from deafferentation and abnormal sympathetic activity.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, 2006. / Bibliyografya var.

Thesis (doctoral)--University of Göteborg, 1993. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--University of Göteborg, 1993. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (MMed.(Anaesthesiology-Faculty of Health Sciences))--University of Pretoria, 2005. / Includes bibliographical references.

Made available in DSpace on 2014-06-11T19:30:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-04Bitstream added on 2014-06-13T20:21:08Z : No. of bitstreams: 1 flores_fn_dr_jabo.pdf: 981909 bytes, checksum: 2f2586723025c784fed157c22e695ca8 (MD5) / A dor é reconhecidamente um dos componentes do trauma com repercussão sistêmica potencialmente prejudicial. A aplicação de anestésicos por via espinhal apresenta vantagens, como emprego de doses reduzidas, além de facilitar o acesso dos fármacos aos seus locais de ação. Os fármacos bloqueadores dos receptores N-metil-D-aspartato (NMDA) têm sido indicados para o controle da hiperalgesia pós-trauma, sendo eficazes mesmo em doses subanestésicas. A cetamina, empregada por via epidural foi eficaz na prevenção da dor somática pós-inciosional em equinos sem efeitos adversos. Contudo a eficácia antinociceptiva dessa substância em dores viscerais tem sido pouco avaliada e permanece controversa. O ifenprodil, um antagonista do sitio das poliaminas, localizado no complexo receptor NMDA, já demonstrou ação antinociceptiva quando associado à cetamina racêmica em cães, porém, seu uso em equinos ainda não foi relatado. Desta forma, em virtude da escassez de informações sobre o efeito analgésico desses bloqueadores do receptor NMDA, aplicados por via espinhal, especialmente na dor visceral nos equinos, propõe-se este estudo para avaliar se existem benefícios no uso da cetamina racêmica isolada ou associada ao ifenprodil na prevenção da dor visceral e somática em equinos / Pain is recognized as one of the components of trauma with potentially harmful systemic impact. The application of anesthetics on spinal pathway has advantages, such as the use of reduced dosages, besides the access facility of drugs to their action sites. The drugs NMDA receptor blockers have been indicated for the control of hyperalgesia following trauma, effective even at under-anesthetic dosages. Ketamine employed by epidural via was effective in preventing post-incisional somatic pain in equinewithout adverse effects. Nevertheless the anti-nociceptive efficacy of that substance in visceral pain has been poorly evaluated and remains controversial. The ifenprodil, a polyamines site antagonist in the NMDA receptor complex, has already demonstrated anti-nociceptive action when associated with racemic ketamine in dogs; however its use in horses has not been reported. Due to the lack of information on the analgesic effect of NMDA receptor blockersapplied via spinal cord, especially in visceral pain in horses, the purpose of this study is to evaluate whether there are benefits in the use of racemic ketamine alone or associated with ifenprodilto prevent somatic and visceral pain in horses