Participation of brainstem nuclei in the pronociceptive effect of lesion or neural block of the anterior pretectal nucleus in a rat model of incisional pain

The anterior pretectal nucleus (APtN) participates in nociceptive process and controls spinal nociceptive inputs, and its integrity reduces the severity of the responses to persistent injury. In this study we examined whether the pedunculopontine tegmental nucleus (PPTg) or the gigantocellularis nucleus pars alpha (GiA), stations that relay APtN inputs to the spinal cord, can control the persistent pain induced by a hind paw incision in rats with disrupted APtN. The withdrawal threshold to mechanical stimulation of the incised paw measured with von Frey filaments was significantly reduced in rats with contralateral APtN lesion or neural block of this nucleus with 2% lidocaine. Intrathecal xylamine, an inhibitor of noradrenaline uptake, inhibited the neural block of the APtN-induced increase in the incisional pain. Injection of glutamate into the contralateral PPTg or ipsilateral GiA reduced the incisional pain. Neural block of the PPTg or GiA reduced the threshold, mainly in APtN-disrupted rats. We conclude that persistent noxious stimulation activates descending pathways involving the contralateral APtN and PPTg, and ipsilateral GiA. Disruption of the APtN allows the activation of alternative circuitry involving at least the PPTg and GiA as intermediary stations that might maintain the control of nociceptive inputs in the spinal cord, probably involving noradrenergic mechanisms.