Title:
Descending modulatory control of pain
Speaker:
Hidemasa Furue 1,2,3
1Dept Information Physiology, National Institute for Physiological Sciences;
2School of Life Science, The Graduate University for Advanced Studies (SOKENDAI]), Myodaiji-cho, Okazaki 444-8787;
3Dept of Neurophysiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan
Abstract:
The locus coeruleus is located in the dorsal pons beneath the floor of the fourth ventricle in the brainstem is one of the principal nuclei that modulate neuronal massages in the CNS including the spinal cord. Locus coeruleus neurons send noradrenergic projections throughout the neuroaxis and are implicated in the control of many homeostatic functions such as arousal, cardio-respiratory control. In addition, the locus coeruleus is also a major source of noradrenergic projections to the spinal superficial dorsal horn which play a significant role in pain modulation.
We have developed in vivo patch-clamp recording techniques from locus coeruleus and spinal superficial dorsal horn neurons1-3) to study the pontospinal noradrenergic control of pain at the synaptic level. Locus coeruleus neurons tested fired spontaneously. Under urethane-anesthesia, whole-cell current- and voltage-clamp recordings were made from locus coeruleus neurons. Cutaneous noxious stimuli applied to the contralateral hind limb transiently increased and then decreased the frequency of action potential discharge in locus coeruleus neurons. Under voltage-clamp conditions, locus coeruleus neurons elicited a small slow current in response to cutaneous noxious stimulation without eliciting any of excitatory postsynaptic currents. When noradrenaline was superfused to the surface of the spinal cord, it induced an outward (hyperpolarizing) current and increased the frequency of inhibitory postsynaptic currents in spinal superficial dorsal horn neurons in vivo. Optoactivation of the locus coeruleus neurons expressing ChR24), however, elicited a barrage of inhibitory postsynaptic currents in spinal superficial dorsal horn neurons without eliciting any postsynaptic slow currents. These results suggest that the locus coeruleus responds to noxious stimulation and the activation of the neurons inhibits spinal nociceptive information mainly through an augmentation of inhibitory synaptic transmission. A sedative agent enexpectively enhanced this descending modulatory system5). The present approaches allow us to analyze detailed characterisation of the synaptic and integrative mechanisms of descending inhibitory control of pain.
References:
1.Furue H et al., Responsiveness of rat substantia gelatinosa neurons to mechanical but not thermal stimuli revealed by in vivo patch-clamp recording, J Physiol. 521: 529-35, 1999.
2.Furue H，In vivo blind patch-clamp recording technique，In: Patch Clamp Techniques: From Beginning to Advanced Protocols (ed, Okada Y)，171-182，Springer, 2012．
3.Sugiyama D et al., In vivo patch-clamp recording from locus coeruleus neurones in the rat brainstem, J Physiol. 590: 2225-31, 2012.
4.Hickey et al, Opto-activation of locus coeruleus neurons evokes bidirectional changes in thermal nociception in rats. J Neurosci. 34(12): 4148-60, 2014
5.Funai Y et al., Systemic dexmedetomidine augments inhibitory synaptic transmission in the superficial dorsal horn through activation of descending noradrenergic control: an in vivo patch-clamp analysis of analgesic mechanisms. Pain 155(3): 617-28, 2014
