Development and characterisation of a novel, anatomically relevant rat model of acute postoperative pain
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Acute postoperative pain remains a significant healthcare issue, delaying discharge and prolonging convalescence periods, resulting in high social and economic costs. Depending on the type of surgical procedure performed, up to half of patients can experience moderate to severe pain in the early hours and days following surgery. Inguinal hernia repair is one of the most common surgical procedures and is increasingly being performed on an ambulatory (day patient) basis. The growth of ambulatory surgery however, is limited by the ability to provide adequate and satisfactory pain relief in the early postoperative period. The development of more anatomically relevant animal models of acute postoperative pain with improved translational and predictive validity will improve our understanding of the mechanisms mediating this condition and allow for the development of more effective pain management protocols. The aims of the work presented in this thesis were to develop and characterise a novel anatomically relevant rat model of acute postoperative pain associated with inguinal hernia repair, and to investigate postoperative pain behaviour using in vivo and ex vivo approaches Under isoflourane anaesthesia, the Lichtenstein inguinal hernia repair technique was employed in male Lister-Hooded rats to model inguinal hernia repair. Post-surgical behavioural characterisation involved extensive investigation of home cage and open field locomotor activity (horizontal and vertical) using the Opto M3 infra-red beam break system. Post-surgical mechanical hypersensitivity using von Frey filaments was also assessed. Bupivacaine, ibuprofen, morphine, carprofen and paracetamol were all investigated for their ability to attenuate surgery-induced deficits in locomotor activity. Further studies interrogated the affective dimension of acute postoperative pain using the place escape avoidance paradigm (PEAP). Immunohistochemistry and liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS) were used to investigate the molecular and neurochemical mechanisms underlying the postoperative behavioural phenotype. Inguinal hernia repair surgery resulted in robust and reproducible deficits in horizontal and vertical locomotor activity in the home cage and open field in the early postoperative period. There was some evidence of slightly increased mechanical hypersensitivity of the inguinal area following surgery, though it was not as robust or reproducible as the locomotor activity deficits. Morphine, carprofen and paracetamol were all capable of attenuating these deficits at discrete time points following surgery. The studies also demonstrate for the first time, an affective component of acute postoperative pain. Furthermore, surgery was associated with increased c-Fos expression in the dorsal horn of the spinal cord and altered levels of endocannabinoids and N-acylethanolamines (NAEs) in the amygdala thalamus and PAG, which may contribute to the observed postoperative behavioural phenotype. In conclusion, these studies support the development and characterisation of a novel, anatomically relevant rat model of acute postoperative pain, which may facilitate development of novel therapeutic approaches for postoperative pain.
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