The anterior pretectal nucleus: a proposed role in sensory processing.

Four nuclei of the pretectal complex, the olivary pretectal nucleus, the medial pretectal nucleus, the nucleus of the optic tract and the posterior pretectal nucleus, all have a demonstrated role in visual function. In contrast, the anterior pretectal nucleus (APtN) has no inputs from retina and has few outputs to visual accessory nuclei. The APtN has connections with areas associated with sensory functions and it has been suggested that this nucleus may have a role to play in somatosensory processing. An increasing number of behavioural and electrophysiological studies support this view. Brief low-intensity electrical or chemical stimulation of the APtN causes antinociception in the tail flick test in both unanaesthetised and anaesthetised animals. This inhibition of the tail flick response is attenuated by naloxone, alpha-adrenoceptor antagonists and muscarinic cholinergic receptor antagonists. Electrical stimulation of the APtN is similarly effective in the paw pressure and formalin tests. APtN stimulation also causes a brief inhibition of the tooth pulp-evoked jaw opening reflex. studies with [C14]2-deoxyglucose indicate that peripheral noxious stimuli will cause an increase in metabolic activity within the APtN. Animals with electrodes placed in the APtN will self-administer electrical stimulation and this can reduce the aversive and autonomic effects of stimulating the ventromedial hypothalamus. Part of the antinociceptive effects of stimulating the APtN are due to a descending inhibition of spinal dorsal horn projection neurones. Multireceptive neurones deep in the dorsal horn are inhibited by APtN stimulation. In contrast, superficial projection neurones that respond to intense cutaneous stimuli are excited by APtN stimulation. The APtN receives an excitatory input from low-threshold afferents via the dorsal column pathway and a high-threshold excitatory drive from superficial cells projecting through the dorsolateral funiculus. The excitatory input from the dorsal columns may well participate in the long-term inhibition of spinal projection neurones evoked by dorsal column stimulation. These ascending excitatory pathways may also be important to the long-term activation of descending inhibition from the APtN.

The antinociception evoked by anterior pretectal nucleus stimulation is partially dependent upon ventrolateral medullary neurones.

Electrical stimulation (35 microA rms/15 s) of the anterior pretectal nucleus (APtN) inhibits the spinal reflex of the tail-flick (TF) to noxious heat in unanaesthetised rats. APtN stimulation also reduces the nociceptive response of spinal dorsal horn neurones in halothane-anaesthetised rats. This study determined if the antinociceptive effects of APtN stimulation depended on neurones in the ventral medulla. Bilateral electrolytic lesions of the ventrolateral medulla, but not the nucleus raphe magnus, reduced by 70% the antinociceptive effect of APtN stimulation in the TF test. In rats anaesthetised with halothane, electrical stimulation of the APtN (single square wave 0.1 msec pulses, 2-20 microA, 1 Hz) excited cells in the ventrolateral medulla. These data suggest a connection between both areas. This connection is further confirmed by neuroanatomical tract tracing studies in which the retrograde dye Fast Blue was injected into the ventrolateral medulla. Fluorescent cell bodies were found in the APtN. We therefore conclude that the ventrolateral medulla is part of a descending antinociceptive pathway from the APtN.

The antinociceptive effects of anterior pretectal stimulation in tests using thermal, mechanical and chemical noxious stimuli.

Four behavioural tests have been used to study the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) in the rat. The antinociceptive effects of stimulating this nucleus, which lies dorsally in the posterior diencephalon, have recently been studied extensively but always using briefly applied heat stimuli. It is reported here that APtN stimulation effectively inhibited responses to briefly applied noxious pressure and longer-lasting noxious chemical (formalin) stimuli. Although the tail-flick reflex to noxious heat was very potently depressed by APtN stimulation, responses to noxious heat in the hot-plate test were not. Three doses of morphine were also studied with each test and it was concluded that 15 sec of 35 microA r.m.s. current into the APtN was as effective as 3-5 mg/kg morphine s.c. in the rat.

The antinociceptive effects of stimulating the pretectal nucleus of the rat.

Changes in the tail-flick latency to noxious heat were studied following electrical stimulation of the dorso-medial thalamus of the rat. Brief (15 sec), low intensity (35 microA) stimulation of the anterior pretectal nucleus caused no escape behavior or motor deficits but increased tail-flick latency for more than 45 min. Responses to non-noxious stimuli were enhanced but the animals were not hyperactive. The anterior pretectal nucleus does not receive retinal or accessory visual inputs like other parts of the pretectal complex but is known to receive axons from somatosensory cortex and project to the perirubral mesencephalic reticular formation and the periaqueductal gray (PAG). The antinociceptive effects of anterior pretectal stimulation were much longer lasting than those of PAG, less disrupting to motor performance and the stimulation was not aversive.