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 (OISDR) in the superficial part of the ipsilateral dorsal horn (DHs). Inhibition of astrocyte metabolism [by bath-applied 400 μM fluoroacetate and 200 μM glutamine (FAc + Gln)] or interference with glial and neuronal K+ transport [by 100 μM 4-aminopyridine (4-AP)] leads to dissociation of the OISDR and the postsynaptic DHs response to a single-pulse, constant-current dorsal root stimulus (P-PSPDR). The OISDR decreases under FAc+Gln, whereas the P-PSPDR remains unaltered; under 4-AP, the P-PSPDR increases, but the OISDR decreases. In contrast, both the OISDR and P-PSPDR increase when K+o is elevated to 8 mM. These observations from slices from normal subjects are interpreted to indicate that the OISDR mainly reflects cell volume and light scattering changes associated with DHs astrocyte uptake of K+ and glutamate (GLU). In slices from subjects that received an intracutaneous injection of formalin 3–5 days earlier, both the OISDR and the response of the DHs ipsilateral to the injection site to 100-ms local application (via puffer pipette) of 15 mM K+ or 100 μM GLU were profoundly reduced, and the normally exquisite sensitivity of the DHs to elevated K+o is decreased. Considered collectively, the observations raise the possibility that impaired regulation of DHs K+o and GLUo may contribute to initiation and maintenance of the CNS pain circuit and sensorimotor abnormalities that develop following intracutaneous formalin injection.