Covariant maturation of nocifensive oral behaviour and c-fos expression in rat superior colliculus.

Injections of formalin into the rodent paw elicit a rapid orientation of the head and mouth to the source of discomfort, followed by licking and biting the injected area. Previous work has shown this response is dependent on the integrity of the midbrain superior colliculus. The present experiments were initiated to examine the ontogeny of this oral nocifensive reaction and to determine whether it is correlated with the functional maturation of collicular responses to noxious stimuli (as indicated by c-fos immunohistochemistry). Rat pups at various postnatal ages received formalin injections in either the hindpaw or perioral regions. Behaviour was videotaped, and after 120 min, animals were killed and the brain and spinal cord processed for Fos-like immunoreactivity. Uninjected controls were treated identically. Formalin-induced oral responses following injections into the hindpaw and the expression of Fos in the superior colliculus were virtually absent until 10 days postnatal, despite the presence of Fos-like immunoreactivity in many other structures (e.g. spinal cord, parabrachial area, periaqueductal grey). In contrast, animals from day 1 were able to use limbs to localise the perioral injection site. From day 10 onward, there was a progressive increase in oral nocifensive behaviours and Fos expression in the superior colliculus. Our observations are consistent with the hypothesis that the normal elaboration of pain-induced oral behaviour is initiated only after a functionally active superior colliculus has developed, and support previous observations that link the colliculus particularly with oral nocifensive behaviours.