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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Interactions between cutaneous afferent inputs to a withdrawal reflex in the decerebrated rabbit and their control by descending and segmental systems.

Previous studies have suggested that activation of nociceptive afferents from the heel recruits a supraspinal mechanism, which is modulated by adrenergic descending inhibition, that augments withdrawal reflexes in medial gastrocnemius (MG) motoneurones. To test this idea, we have studied the temporal evolution of reflexes evoked in MG by electrical stimulation of sural nerve A(beta)-, A(delta)- and C-fibre axons at 1 Hz, in decerebrated rabbits. Reflexes were analysed in three time bands, estimated to accord to afferent drive from A(beta)- (phase 1), A(delta)- (phase 2) and C-fibre (phase 3) inputs. Stimulation of A(delta)- and C-fibres gave significant temporal summation of all reflexes. The alpha(2)-adrenoceptor antagonist RX 821002 ((2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1-H-imidazole)-HCl) (100 microg intrathecal (i.t.)) potentiated, and the alpha(2)-agonist dexmedetomidine (1-30 microg i.t.) depressed all reflexes per se, but the effects of these drugs on temporal summation were secondary to changes in baseline excitability. When C-fibres were stimulated, the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (1 mg i.t.) reduced temporal summation of phase 2 and 3 but not phase 1 reflexes. Spinalisation at L1 in the absence of drugs increased phase 2 and 3 reflexes but had no effect on phase 1, whereas spinalisation after RX 821002 resulted in decreased phase 1 responses with no significant change in later phases. Spinalisation in the presence of dizocilpine resulted in small reductions in phase 3 reflexes only. In all cases spinalisation virtually abolished temporal summation. In spinalised animals, dizocilpine selectively reduced late reflexes, and the opioid antagonist naloxone (100 microg i.t.) augmented all reflexes but gave rise to temporal subtraction of reflexes when C-fibres were stimulated.The present experiments have revealed a number of novel and important features of the sural-MG reflex pathway: (i) activity in fine afferent axons augments the reflexogenic potential of all subsequent afferent input, thereby allowing all afferent drive from the sural field to contribute to withdrawal of the heel; (ii) endogenous adrenergic control of this reflex pathway is completely non-selective; (iii) there is a non-adrenergic element of descending inhibition that is selective for the late components of MG reflex responses, and this element is directed particularly against transmission through NMDA receptors; (iv) temporal summation in this reflex is dependent on NMDA receptor-dependent and -independent mechanisms; and (v) this temporal summation is in some way dependent on the integrity of descending pathways.[1]


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