Inhibitory mechanisms are essential in suppressing the development of
allodynia and
hyperalgesia in the normal animal and there is evidence that loss of inhibition can lead to the development of
neuropathic pain. We used Fos expression to map the distribution of tonically inhibited cells in the healthy rat lumbar spinal cord. In a control group, Fos-like immunoreactive (Fos-LI) cells were rare, averaging 7.5+/-2.2 cells (mean+/-SEM; N=13 sections) per 20 microm thick section of dorsal horn. This rose to 103+/-11 (mean+/-SEM; N=20) in
picrotoxin-treated rats and to 88+/-11 (mean+/-SEM; N=18) in
strychnine-treated rats. These changes were significant (ANOVA; P<0.001). There were marked regional variations in the distribution of Fos-LI cells between
picrotoxin- and
strychnine-treated animals.
Picrotoxin induced a significant increase in the number of Fos-LI cells throughout the dorsal horn (lamina I-VI) while
strychnine significantly elevated Fos-like immunoreactivity only in deep laminae (III-VI). For both
picrotoxin and
strychnine, the increase in Fos-like immunoreactivity peaked in lamina V (at 3579+/-319 and 3649+/-375% of control, respectively; mean+/-SEM) but for
picrotoxin an additional peak was observed in the outer part of lamina II (1959+/-196%). Intrathecal administration of both GABAA and
glycine receptor antagonists has been shown elsewhere to induce
tactile allodynia. The present data suggest that this
allodynia could arise due to blockade of tonic GABAA and
glycine-receptor mediated inhibition in the deep dorsal horn. GABAA antagonists also induce
hypersensitivity to noxious inputs. The blockade of tonic inhibition in the superficial dorsal horn shown here may underlie this
hyperalgesia.