Up-Regulation of Pain Behavior and Glial Activity in the Spinal Cord after Compression and Application of Nucleus Pulposus onto the Sciatic Nerve in Rats

Norimoto, Masaki; Sakuma, Yoshihiro; Suzuki, Miyako; Orita, Sumihisa; Yamauchi, Kazuyo; Inoue, Gen; Aoki, Yasuchika; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Kamoda, Hiroto; Kubota, Gou; Oikawa, Yasuhiro; Inage, Kazuhide; Sainoh, Takeshi; Sato, Jun; Nakamura, Junichi; Toyone, Tomoaki; Takahashi, Kazuhisa; Ohtori, Seiji

Abstract

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission.
METHODS
The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively.
RESULTS
Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05).
CONCLUSIONS
Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.