Pain: morphine, metabolites, mambas, and mutations

  title={Pain: morphine, metabolites, mambas, and mutations},
  author={Clifford J. Woolf},
  journal={The Lancet Neurology},
  • C. Woolf
  • Published 31 January 2013
  • Medicine, Psychology
  • The Lancet Neurology
Breaking barriers to novel analgesic drug development
Recent advances in the understanding of the neurobiology of pain are beginning to offer opportunities for developing novel therapeutic strategies and revisiting existing targets, including modulating ion channels, enzymes and G-protein-coupled receptors.
Cannabinoid Receptor Type 1 and Its Role as an Analgesic: An Opioid Alternative?
Evidence is provided that one of the main roles of the endocannabinoid system is the regulation of gamma-aminobutyric acid (GABA) and/or glutamate release and its implications for pain.
[Acid-Sensing Ion Channels (ASICs) in pain].
The discovery of new drug targets represents a real opportunity for developing fresh strategies against pain and data suggesting a role in human pain suggests the therapeutic potential of acid-Sensing Ion Channels.
Binding Site and Inhibitory Mechanism of the Mambalgin-2 Pain-relieving Peptide on Acid-sensing Ion Channel 1a*
A model where mambalgin-2 traps the channel in a closed conformation by precluding the conformational change of the palm and β-ball domains that follows proton activation is proposed.
Mambalgin-1 Pain-relieving Peptide, Stepwise Solid-phase Synthesis, Crystal Structure, and Functional Domain for Acid-sensing Ion Channel 1a Inhibition*
The first full stepwise solid phase peptide synthesis of mambalgin-1 is shown and the biological activity of the synthetic toxin both in vitro and in vivo is confirmed and the determination of its three-dimensional crystal structure showing differences with previously described NMR structures is reported.
Acupuncture for Pediatric Pain
Acupuncture can be an effective adjuvant in the care of pediatric patients with painful conditions, both in a chronic and an acute setting, and further studies, including randomized controlled trials, as well as trials of comparative effectiveness are needed.
Medical Science Turns Deadly Substances into Life Saving Ones: Snake Venom as a Treatment Option
The aim of current research is to make people realize that the snake venom, despite being a deadly poison, may prove to be a treatment option in several rather incurable diseases.
Perioperative management in children with chronic pain
Identification of the pediatric chronic pain patient preoperatively and development of a perioperative pain plan may help ensure a safer and more comfortable perioperatively course.


Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy
It is found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain, which provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy.
Crystal structure of the μ-opioid receptor bound to a morphinan antagonist
The 2.8 Å crystal structure of the mouse µ-OR in complex with an irreversible morphinan antagonist is described, revealing high-resolution insights into opioid receptor structure that will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.
Corticostriatal functional connectivity predicts transition to chronic back pain
In a longitudinal brain imaging study, subacute back pain patients were followed over the course of 1 year and brain gray matter density decreased, implying that corticostriatal circuitry is causally involved in the transition from acute to chronic pain.
Gain of function NaV1.7 mutations in idiopathic small fiber neuropathy
Screening patients with biopsy‐confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage‐gated sodium channel NaV1.7, which is preferentially expressed in small diameter peripheral axons, identifies a genetic basis for I‐SFN.
Combined small molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors
The quick and high-efficiency derivation of nociceptors offers unprecedented access to this medically relevant cell type for studies of human pain, and use of small-molecule pathway inhibitors could become a general strategy for accelerating developmental timing in vitro.
Gain of function Nav 1 . 7 mutations in idiopathic small fi ber neuropathy
  • Ann Neurol
  • 2012