c-Fos antisense oligodeoxynucleotide offsets behavioral nociceptive responses and both up-regulations of c-Fos protein and dynorphin a (1-8) in dorsal horn: a study using the formalin test in rats.
The formalin test was used to elicit acute and chronic pain in rats, and antisense oligodeoxynucleotide (AS-ODN) was used as a tool to modulate the expression of nociceptive behavioral and neurochemical responses. AS-ODN complementary to c-Fos mRNA was administered intrathecally (i.t.) 4 h before formalin injection in the experimental group. Normal saline or reverse AS-ODN was pre-administered i.t. at the same time in two control groups (saline and reverse AS-ODN). The results showed that the acute phase of nociceptive behavior showed no change by AS-ODN administration, whereas the tonic phase of nociceptive licking and biting behavior was significantly suppressed by AS-ODN as compared with the saline or the reverse AS-ODN group, respectively (p < .05 and p < .01). At the same time, both Fos-like immunoreactive (FLI) neurons and density of dynorphin-like immunoreactivities (DLI) were decreased significantly (p < .05 and p < .01) in the AS-ODN group as compared with that in two control groups. The results indicate that the long-lasting nociceptive responses elicited by sustained noxious inputs are based on the up-regulation of c-Fos gene expression, which in turn induces the upregulation of Dyn A production. It is proposed that intensified Dyn A production in the dorsal horn may be pivotal for the appearance of chronic pain.
Zhang
Yu
Y
Department of Neurobiology, Shanxi Medical University, Taiyuan, PR China.
Qiao
Jian-Tian
JT
Dafny
Nachum
N
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004399:Dynorphins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005557:Formaldehyde; D007278:Injections, Spinal; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage*; D010146:Pain / Q000139:chemically induced; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
D020319:Oligodeoxyribonucleotides, Antisense; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D005557:Formaldehyde; D004399:Dynorphins; C026770:dynorphin (1-8)