FIG. 2.

Induction and regulation of nociceptive sensitization after spinal injury. (A) Spinal injury can disrupt descending fibers that normally quell overexcitation within the dorsal horn, enabling development of central sensitization. (B) Relational learning can attenuate nociceptive sensitization and enable adaptive plasticity. Learning depends upon cues that indicate a nociceptive stimulus occurs at a particular position (the R) or time. (C) Variable intermittent shock (red) enhanced reactivity to mechanical stimulation in spinally transected rats. (D) Application of capsaicin to one hindpaw impaired instrumental learning. Spinally transected rats were tested by applying response-contingent shock to the contralateral hindleg. In the absence of capsaicin treatment (white circles), training induced a progressive increase in flexion duration that reduced net shock exposure. Application of capsaicin (green circles) impaired learning. (E) Past exposure to controllable stimulation blocked the development of capsaicin-induced EMR. Spinally transected rats had received 30 min of instrumental training (Master, green), or nothing (Unshk, red), before the application of capsaicin to the same limb. Subjects were then tested by applying mechanical stimuli (von Frey) to the plantar surface of the injected and uninjected paw. Capsaicin treatment induced EMR in naïve (unshocked) subjects. Previous experience with controllable stimulation (Master) attenuated this effect. (F) Previous training with controllable stimulation blocked the capsaicin-induced learning impairment. Spinally transected rats were given 30 min of instrumental training (Master, green), or nothing (Unshocked, red), before the application of capsaicin to the same limb. Subjects were then tested by applying response-contingent shock to the contralateral leg. Capsaicin treatment impaired learning in the naïve (Unshocked) subjects. Past experience with controllable stimulation eliminated this learning impairment. EMR, enhanced mechanical reactivity.