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

Abstract

In rat spinal cord, slice repetitive electrical stimulation of the dorsal root at an intensity that activates C-fibers evokes a slow-to-develop and prolonged (30-50 s) change in light transmittance (OIS(DR)) in the superficial part of the ipsilateral dorsal horn (DH(s)). Inhibition of astrocyte metabolism [by bath-applied 400 microM fluoroacetate and 200 microM glutamine (FAc + Gln)] or interference with glial and neuronal K+ transport [by 100 microM 4-aminopyridine (4-AP)] leads to dissociation of the OIS(DR) and the postsynaptic DH(s) response to a single-pulse, constant-current dorsal root stimulus (P-PSP(DR)). The OIS(DR) decreases under FAc+Gln, 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(+)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+ 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+ or 100 microM GLU were profoundly reduced, and the normally exquisite sensitivity of the DH(s) to elevated K(+)o is decreased. Considered collectively, the observations raise the possibility that impaired regulation of DH(s) K(+)o and GLU(o) may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities that develop following intracutaneous formalin injection.