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
N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic
acid (
AMPA)/
kainate receptors for
pain behaviors indicating secondary
hyperalgesia caused by gastrocnemius incision in the rat. We further determined if Ca(2+) permeable
AMPA/
kainate receptors are important for secondary
hyperalgesia after gastrocnemius incision and for
pain behaviors indicating primary
hyperalgesia and guarding behavior after plantar incision. Withdrawal thresholds (WTs) to punctate mechanical stimuli were assessed by applying calibrated monofilaments to the plantar hind paw before gastrocnemius incision. WTs were tested again 2 h after gastrocnemius incision and again after intrathecal (IT) injection of either
dizocilpine maleate (MK-801),
2-amino-5-phosphonovaleric acid (AP5), 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo[f]
quinoxaline-7-
sulfonamide (
NBQX), or
Joro spider toxin (
JSTX). The doses used were:
MK-801 (vehicle, 15, 30, 40 nmol), AP5 (vehicle, 10, 30 nmol),
NBQX (vehicle, 5, 10 nmol), and
JSTX (vehicle, 2, 5, 9 nmol). In the same rats, WTs were tested on postoperative day 2 before and after the same drugs were injected again. In other rats, WTs to monofilaments and response frequencies to a non-punctate mechanical stimulus or guarding behaviors were determined before, 1 h after plantar incision was made, and assessed again after
JSTX (9 nmol or vehicle) was administered IT. Secondary
mechanical hyperalgesia after gastrocnemius incision was dose-dependently blocked by
NBQX but was only marginally affected by AP5 or
MK-801. Only secondary
mechanical hyperalgesia was reversed by
JSTX; primary
mechanical hyperalgesia and guarding behavior were unchanged. These results indicate that spinal sensitization contributing to behaviors for secondary
hyperalgesia after incision requires Ca(2+) permeable
AMPA/
kainate receptors. The data further demonstrate that behaviors for secondary
mechanical hyperalgesia after incision can be inhibited without affecting behaviors for 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.