Optically Recorded Response of the Superficial Dorsal Horn: Dissociation From Neuronal Activity, Sensitivity to Formalin-Evoked Skin Nociceptor Activation

Abstract

. The OIS DR decreases under FAcϩGln, whereas the P-PSP DR remains unaltered; under 4-AP, the P-PSP DR increases, but the OIS DR decreases. In contrast, both the OIS DR and P-PSP DR increase when K ϩ o is elevated to 8 mM. These observations from slices from normal subjects are interpreted to indicate that the OIS DR mainly reflects cell volume and light scattering changes associated with DH s astrocyte uptake of K ϩ and glutamate (GLU). In slices from subjects that received an intracutaneous injection of formalin 3-5 days earlier, both the OIS DR and the response of the DH s ipsilateral to the injection site to 100-ms local application (via puffer pipette) of 15 mM K ϩ or 100 M GLU were profoundly reduced, and the normally exquisite sensitivity of the DH s to elevated K ϩ o is decreased. Considered collectively, the observations raise the possibility that impaired regulation of DH s K ϩ o and GLU o may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities that develop following intracutaneous formalin injection.

Attenuated Glial K+ Clearance Contributes to Long-Term Synaptic Potentiation Via Depolarizing GABA in Dorsal Horn Neurons of Rat Spinal Cord

“…1B) failed to significantly alter either the magnitude or time course of the reduction of the OIS DR that followed exposure to FC. Consistent with the demonstration that magnitude of the OIS DR depends on glutamatergic neurotransmission [4, 21], APV application alone led to a modest suppression of the OIS DR (plot with gray squares at Fig. 1B) that reversed and returned to control levels 20~25 min after the perfusion solution was restored to drug-free, normal ACSF.…”

“…Observations reported in previous studies are fully consistent with the idea that impairment of the ability of astrocytes to regulate extracellular K + and glutamate levels alters excitatory neurotransmission at multiple levels of the CNS. As examples: (1) the secondary hyperalgesia that follows intradermal injection of 5% formalin is accompanied by an impaired ability of astrocytes to regulate [K + ] o and [glutamate] o in the region of the DH s that receives its input from the injected skin site [4, 5], (2) even a brief (40 sec) increase in extracellular K + induces LTP in the hippocampal slice [6]; (3) hippocampal LTP is substantially reduced in animals in which astrocytes are rendered unable (via a selective genetic manipulation) to release neurotransmitters [7]; (4) d-serine released from astrocytes is critical for the induction of LTP in hippocampal slices [8]; (4) the slow astrocytic depolarization that accompanies hippocampal LTP is due to astrocyte uptake of K + and supports neuronal LTP by reducing the efficacy of astrocytic glutamate transporters and inducing astrocyte release of a variety of signaling molecules (for review see [9]); and, finally, (5) intracerebral injection of fluorocitrate (a reversible, selective inhibitor of glial metabolism, [5, 10]) elevates [K + ] o , increases cortical neuron excitability, and induces focal epileptiform discharge [11]. …”

“…The goals of this study were to: (1) investigate the possibility that transient impairment of spinal cord glial energy metabolism can, in the absence of a preceding period of conditioning afferent drive, initiate the long-term enhancement of DH s excitatory synaptic transmission widely regarded to underlie central sensitization, secondary hyperalgesia, and persistent pain [3, 12]; and, (2) acquire information bearing directly on the validity of the recent proposal that impaired astrocytic regulation of [K + ] o can lead to conversion of the effect of GABA on DH s neurons from inhibition to excitation [4, 13, 14]. …”

Dynamic representations of the somatosensory cortex

“…Initially, we regarded this very slow decay of the OIS as having little or no physiological significance. This interpretation proved premature, however, because in vitro studies carried out in parallel with our in vivo studies (Kohn et al, 2000;Lee et al, 2005) revealed that the OIS, while providing an accurate indication of the locus and magnitude of local neuronal activation, is not directly attributable to neuronal activity. Instead, our studies of spinal cord and sensorimotor cortical slices convincingly revealed that the OIS is the result of astrocytic swelling due to uptake (along with water) of the excess extracellular K+ and neurotransmitters (e.g., glutamate) released during excitatory neurotransmission.…”

Amplitude-dependency of response of SI cortex to flutter stimulation

“…The OIS obtained using infrared light has been shown to be highly correlated with light scattering effects that accompany astrocyte swelling subsequent to the clearance of extracellular K + and neurotransmitter [14,15,18] and local increases in blood volume [19,20]. Although the OIS at this wavelength may be influenced by changes in hemoglobin concentration and oxygenation, it is likely that contributions from these factors are small when compared with light scattering effects[20].…”