Spinale Glutamatrezeptorantagonisten: Differenzierung von primärer und sekundärer mechanischer Hyperalgesie nach operativer Schnittinzision im Tierexperiment

Abstract

Secondary mechanical hyperalgesia has been demonstrated in postoperative patients indicating that central sensitization occurs after surgery. However, the underlying mechanisms are unknown. Here, we studied the role of spinal AMPA/kainate receptors for pain behaviors indicating secondary hyperalgesia caused by gastrocnemius incision in the rat. These were reduced by NBQX, a selective antagonist of AMPA/kainate receptors. However, administration of NMDA receptor antagonists caused no or only a modest decrease in behaviors for secondary hyperalgesia but produced associated motor deficits and supraspinal side effects. We further determined that only secondary mechanical hyperalgesia was reversed by JSTX, a selective antagonist of calcium-permeable AMPA receptor; primary mechanical hyperalgesia and guarding behavior were unchanged. These findings indicate that JSTX influenced a spinal amplification process that leads to secondary hyperalgesia but does not contribute to primary hyperalgesia and guarding after incision. This amplification process likely requires Ca(2) influx through spinal AMPA/KA (but not NMDA) receptors. Behaviors for secondary mechanical hyperalgesia after incision can be inhibited without affecting primary mechanical hyperalgesia and guarding. Mechanisms for central sensitization causing secondary hyperalgesia in postoperative patients may therefore be separated from spontaneous pain and hyperalgesia that arises adjacent to the area of the incision.

Serotonin Receptors are Involved in the Spinal Mediation of Descending Facilitation of Surgical Incision-Induced Increase of Fos-Like Immunoreactivity in Rats

“…They have shown that noradrenergic receptors are involved in the spinal mediation of descending inhibitory pathways in the primary hyperalgesia of postoperative pain [29,49,51]. Few reports are also available regarding secondary hyperalgesia after post-incision pain [47,89-94] but, as far we know, none of them have studied spinal neurotransmitters involved in descending mechanisms.…”