David Berg
10-31-2003, 03:51 PM
Dejerine has hinted at this a bit, but there's some research that was published recently that deserves a lot more attention. Published in Nature on 23 August 2003, Coull et al have made an astonishing discovery. In severe chronic pain, such as central pain, inhibitory nerve pathways are basically turned into excititory pathways capable of transporting pain. Sounds like double the pain messages pouring in with nothing head off the flood of pain. They obviously have some good work going on up at McGill University.
Here's the abstract from PubMed.com:
Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain.
Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, De Koninck P, De Koninck Y.
Neurobiologie Cellulaire, Centre de recherche Universite Laval Robert-Giffard, Quebec, Quebec G1J 2G3, Canada.
Modern pain-control theory predicts that a loss of inhibition (disinhibition) in the dorsal horn of the spinal cord is a crucial substrate for chronic pain syndromes. However, the nature of the mechanisms that underlie such disinhibition has remained controversial. Here we present evidence for a novel mechanism of disinhibition following peripheral nerve injury. It involves a trans-synaptic reduction in the expression of the potassium-chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways. In our experiments, the resulting shift in the transmembrane anion gradient caused normally inhibitory anionic synaptic currents to be excitatory, substantially driving up the net excitability of lamina I neurons. Local blockade or knock-down of the spinal KCC2 exporter in intact rats markedly reduced the nociceptive threshold, confirming that the reported disruption of anion homeostasis in lamina I neurons was sufficient to cause neuropathic pain.
PMID: 12931188 [PubMed - indexed for MEDLINE]
Here's the abstract from PubMed.com:
Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain.
Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, De Koninck P, De Koninck Y.
Neurobiologie Cellulaire, Centre de recherche Universite Laval Robert-Giffard, Quebec, Quebec G1J 2G3, Canada.
Modern pain-control theory predicts that a loss of inhibition (disinhibition) in the dorsal horn of the spinal cord is a crucial substrate for chronic pain syndromes. However, the nature of the mechanisms that underlie such disinhibition has remained controversial. Here we present evidence for a novel mechanism of disinhibition following peripheral nerve injury. It involves a trans-synaptic reduction in the expression of the potassium-chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways. In our experiments, the resulting shift in the transmembrane anion gradient caused normally inhibitory anionic synaptic currents to be excitatory, substantially driving up the net excitability of lamina I neurons. Local blockade or knock-down of the spinal KCC2 exporter in intact rats markedly reduced the nociceptive threshold, confirming that the reported disruption of anion homeostasis in lamina I neurons was sufficient to cause neuropathic pain.
PMID: 12931188 [PubMed - indexed for MEDLINE]