Optically recorded response of the superficial dorsal horn: dissociation from neuronal activity, sensitivity to formalin-evoked skin nociceptor activation.
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.
Lee
Jaekwang
J
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599-7545, USA.
Tommerdahl
M
M
Favorov
O V
OV
Whitsel
B L
BL
D015761:4-Aminopyridine / Q000494:pharmacology; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D005463:Fluoroacetates / Q000494:pharmacology; D005557:Formaldehyde / Q000009:adverse effects*; D007839:Functional Laterality; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012867:Skin / Q000294:innervation* / Q000528:radiation effects; D013116:Spinal Cord / Q000166:cytology*; D013997:Time Factors
D000777:Anesthetics; D005463:Fluoroacetates; D026902:Potassium Channel Blockers; D005557:Formaldehyde; D018698:Glutamic Acid; D008012:Lidocaine; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium