Laminar distribution of GABAA- and glycine-receptor mediated tonic inhibition in the dorsal horn of the rat lumbar spinal cord: effects of picrotoxin and strychnine on expression of Fos-like immunoreactivity.
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.
Cronin
John N
JN
Department of Physiology, Hodgkin Building, King's College London, London SE1 1UL, UK.
Bradbury
Elizabeth J
EJ
Lidierth
Malcolm
M
D000818:Animals; D058787:GABA-A Receptor Antagonists; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007120:Immunochemistry; D008159:Lumbar Vertebrae / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology*; D020671:Posterior Horn Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000032:analysis / Q000096:biosynthesis; D018009:Receptors, Glycine / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013331:Strychnine / Q000494:pharmacology*
D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D016760:Proto-Oncogene Proteins c-fos; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D013331:Strychnine