Allodynia and hyperalgesia produced by specific inhibition of spinal c-fosexpression: Lack of correlation with dynorphin content

Inhibition of spinal Fos expression increases formalin-induced nociception and decreases spinal prodynorphin messenger ribonucleic acid (mRNA), sugges ting that Fos modulates nociception by inducing dynorphin synthesis. This s tudy tests the hypothesis that Fos modulates sensitivity to other somatic s timuli, such that inhibition of Fos expression will result in tactile allod ynia and thermal hyperalgesia. In addition, it correlates the somatosensory effects of inhibition of Fos expression with spinal dynorphin content. Ant isense oligodeoxynucleotide (ODN) to c-fos mRNA was administered by intrath ecal infusion. Tactile sensitivity was tested by probing the hindpaw with v on Frey filaments. Thermal sensitivity was quantitated by using withdrawal latency to radiant heat. Two percent formalin was injected into the dorsal hindpaw, and flinches were quantitated. Fos was quantitated by counting imm unoreactive cells. Dynorphin was measured by immunoassay. Intrathecal antis ense, but not mismatch, ODN resulted in tactile allodynia, thermal hyperalg esia, and hyperalgesia to formalin-induced nociception. Antisense ODN decre ased Fos-like immunoreactivity after formalin injection but did not alter J un-like immunoreactivity. Antisense ODN had differing effects on spinal dyn orphin content, depending an the method of administration. These experiment s show a role of Fos in modulating somatosensory sensitivity and suggest th at induction of dynorphin synthesis is not the sole mechanism by which Fos does so. (C) 2001 by the American Pain Society.