Controls of tachykinin release in the mammalian spinal cord

The purpose of this series of investigations was to elucidate the endogenous control mechanisms active at primary afferent terminals of nociceptive origin in the dorsal laminae of the spinal cord grey matter. Such studies may enable the researcher to make certain conclusions about endogenous mechanisms of pain control in vivo. Furthermore, these studies may help to identify novel areas for the development of analgesic drugs or protocols of therapeutic value in both human and veterinary pain management.

Experiments were centred on one particular family of neuropeptides, the tachykinin peptides, and their release in response to peripheral noxious stimulation as determined by the antibody microprobe technique. A review of the anatomy and physiology of tachykinins in the spinal cord is presented at the start of this thesis. The antibody microprobe technique itself is also fully described.

Various means of modulating tachykinin release pharmacologically were tested and are presented in this thesis. The results presented here relate to studies on 1) morphine, 2) noradrenaline and the imidazoline derivative drug, medetomidine, 3) neuropeptide Y. A short review on the pharmacological actions of each of these drugs is included. All the results presented are derived from experiments on barbiturate anaesthetised, spinalised cats.