Fig. 4. Neuropathic pain is not altered by the intrathecal application of the QX-314/capsaicin combination. After ligating the right sciatic nerve, the withdrawal thresholds to mechanical (A , C , and E ) and thermal (B , D , and F ) stimuli decreased for the side ipsilateral to the nerve ligation (Ligated). The thresholds were not reduced for the paw contralateral to the ligation (Control, n = 5). Typically, this hyperalgesia developed within 4–10 days after the surgery. For the paw ipsilateral to the nerve ligation, the QX-314/capsaicin combination (0.2% QX-314 + 0.5 mg/ml capsaicin, n = 5) did not change the withdrawal threshold to mechanical or thermal stimuli. Surprisingly, the QX-314/capsaicin combination decreased the mechanical threshold of the control (nonligated) leg. QX-314 (0.2%, n = 6) alone also reduced the mechanical threshold of the control leg without relieving the mechanical allodynia. However, QX-314 did partially reverse the thermal hyperalgesia for the ipsilateral foot. The vehicle had no effect on the mechanical or thermal thresholds for the ligated or control paws. Insertion of osmotic pumps containing drugs is indicated by the dashed line. *P < 0.05 compared with the control (unligated) paw. Cap = capsaicin; QX = QX-314.