Involvement of the anterior pretectal nucleus in the control of persistent pain: a behavioral and c-Fos expression study in the rat

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Abstract
The anterior pretectal nucleus (APtN) participates in nociceptive processing and in the activation of central descending mechanisms of pain control. In this study we used behavioral tests (incisional pain and carrageenan-induced inflammatory pain) and c-Fos expression changes to examine the involvement of the APtN in the control of persistent pain in rats. A 1cm longitudinal incision through the skin and fascia of the plantar region (large incision), or a 0.5cm longitudinal incision through the skin only (small incision) was used, and the postoperative incisional allodynia was evaluated with von Frey filaments. The hyperalgesia produced by the intraplantar administration of carrageenan (25 or 50 microg/100 microl) into a hind paw was evaluated by a modified paw pressure test. The electrolytic lesion of the contralateral, but not ipsilateral, APtN significantly intensified the allodynia produced by a large incision of the hind paw. The incisional allodynia and the carrageenan-induced hyperalgesia were intensified by the microinjection of 2% lidocaine into the contralateral, but not ipsilateral APtN, the effect being significantly stronger when a large incision or a higher carrageenan concentration was utilized. A significant increase in the number of c-Fos positive cells was found in the ipsilateral, and mainly in the contralateral APtN of rats submitted to a large incision. The number of positive cells in the superficial or deep laminae of the contralateral spinal cord of control and incised rats was not significantly different. Positive cells in the superficial or deep laminae of the ipsilateral spinal cord were significantly more numerous than in control, the effect being significantly more intense in rats with large incision. The microinjection of 0.5% bupivacaine into the APtN contralateral to the incised hind paw reduced the number of positive cells bilaterally in the APtN, but the effect was significant in the contralateral nucleus only. The number of positive cells in the superficial and deep laminae of the contralateral spinal cord of incised and non-incised animals was not significantly changed by the neural block of the contralateral APtN. In the ipsilateral spinal cord, the incision-induced increase in the number of positive cells was significantly reduced in the superficial lamina and significantly increased in the deep lamina of animals previously treated with bupivacaine in the contralateral APtN. In conclusion, the integrity of the APtN is necessary to reduce the severity of the responses to persistent injury. The results also are in agreement with the current notion that persistent noxious inputs to the APtN tonically activate a descending mechanism that excites superficial cells and inhibits deep cells in the spinal dorsal horn.