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The development and evaluation of tourniquet-induced post-ischaemic allodynia : a method for investigating the mechanism of and treatment for chronic pain Pau, Hin-Chung Clifford

Abstract

Allodynia and hyperalgesia are two aspects of chronic pain for which understanding of their mechanisms and available treatments are currently inadequate. Currently available methods for investigating allodynia and hyperalgesia are generally invasive. The objective of this project was to evaluate tourniquet-induced postischaemic allodynia in mice - a potentially less invasive method for studying chronic pain. In the present study, a tourniquet was applied at the base of a mouse tail in order to induce post-ischaemic allodynia at the distal extremity. We quantified the tourniquet-induced post-ischaemic allodynia in mice with respect to its time course. The following two characteristics of post-ischaemic allodynia were observed with an increasing duration of tourniquet application: (1) Increase in onset time of the appearance of tourniquet-induced post-ischaemic allodynia, and (2) increase in the total duration of the tourniquet-induced post-ischaemic allodynia. The pharmacology associated with the induced allodynia was also investigated in this project. The effects of standard analgesic agents and local anaesthetic drugs were tested, and they were found to be effective in blocking pinprick pain and post-ischaemic allodynia in mice. However, none of the tested drugs were found to be effective in blocking the development of tourniquet-induced post-ischaemic allodynia in mice. We have also demonstrated how the method used to induce allodynia in mice could be applied to the study of the mechanism of and treatment for tourniquet-induced post-ischaemic allodynia. Systemic lidocaine was found to block both pinprick pain and post-ischaemic allodynia in mice centrally (in the spinal cord or higher level in the central nervous system) rather than peripherally (at the peripheral nerve endings), since its action was not prevented by exclusion of the drug from the site of pain generation. Morphine was equally effective in blocking pinprick pain and allodynic pain via an action presumptively only on the central nervous system, since its effect was not dependent on its reaching the site of pain generation. Morphine did not prevent the induction of post-ischaemic allodynia.

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