Roman Cregg

Neurological perspectives on voltage-gated sodium channels.

The activity of voltage-gated sodium channels has long been linked to disorders of neuronal excitability such as epilepsy and chronic pain. Recent genetic studies have now expanded the role of sodium channels in health and disease, to include autism, migraine, multiple sclerosis, cancer as well as muscle and immune system disorders. Transgenic mouse models have proved useful in understanding the physiological role of individual sodium channels, and there has been significant progress in the development of subtype selective inhibitors of sodium channels. This review will outline the functions and roles of specific sodium channels in electrical signalling and disease, focusing on neurological aspects. We also discuss recent advances in the development of selective sodium channel inhibitors.

Pain channelopathies: Pain channelopathies

Pain remains a major clinical challenge, severely afflicting around 6% of the population at any one time. Channelopathies that underlie monogenic human pain syndromes are of great clinical relevance, as cell surface ion channels are tractable drug targets. The recent discovery that loss‐of‐function mutations in the sodium channel Nav1.7 underlie a recessive pain‐free state in otherwise normal people is particularly significant. Deletion of channel‐encoding genes in mice has also provided insights into mammalian pain mechanisms. Ion channels expressed by immune system cells (e.g. P2X7) have been shown to play a pivotal role in changing pain thresholds, whilst channels involved in sensory transduction (e.g. TRPV1), the regulation of neuronal excitability (potassium channels), action potential propagation (sodium channels) and neurotransmitter release (calcium channels) have all been shown to be potentially selective analgesic drug targets in some animal pain models. Migraine and visceral pain have also been associated with voltage‐gated ion channel mutations. Insights into such channelopathies thus provide us with a number of potential targets to control pain.

Perioperative myocardial infarction in a patient receiving low-dose prothrombin complex concentrates

Perioperative myocardial infarction in a patient receiving low-dose prothrombin complex concentrates -

Postoperative pain management

This article provides an overview of current methods used in acute pain management and explains why effective analgesia is crucial in the early postoperative period. It describes the pharmacology of both common and specialist analgesics, as well as explaining the role and uses of regional and neuraxial analgesia, for the non-anaesthetist.