Watterson, G.; (2007) The efficacy and mechanism of peripheral opioids in paediatric inflammatory pain. Doctoral thesis , University of London.

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Abstract

Background: The management of pain in children is a common but difficult symptom to treat and the use of strong analgesics is often limited, for a variety of reasons, including fear of inducing side effects. Morphine is normally considered to be a centrally acting analgesic but recently, the beneficial effects of peripheral opioids have been demonstrated in adults for a number of painful inflammatory conditions. When administered in this non invasive way, opioids provide analgesia without achieving significant plasma concentrations and therefore it can be assumed that many of the adverse effects associated with oral or systemic opioids are avoided. Methods: A) The first part of the thesis describes the mechanism of action of peripheral opioids through development and particularly their effect during inflammation. This work was conducted using different ages of Sprague Dawley rat pups and skin inflammation was induced using carageenan. B) The second section is a description of a double-blinded, randomised-controlled, placebo-controlled trial with crossover design, to assess the efficacy of peripheral opioids in paediatric inflammatory pain. This was conducted in children with a diagnosis of Epidermolysis Bullosa (EB), as a model for acute and chronic inflammatory pain Results:. The laboratory study demonstrates that mu opioid receptor (MOR) expression is up regulated in neonatal plantar skin and significantly up regulated in neonatal lumbar dorsal root ganglion (DRG) four hours post hind paw inflammation, MOR protein levels in the rat hind paw plantar skin are significantly up regulated post-natally, and MOR protein levels are significantly up regulated in both neonatal and young adult plantar skin four hours post hind paw inflammation. Clinically, pain reduction was most significant with background pain Conclusion: The developmental regulation of peripheral MOR both in naive and inflamed cutaneous tissue may have implications for the use of topically / peripherally applied opioids in infants and children. "I, Gillian Watterson confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis".

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