Central analgesic effect of paracetamol manifested by depression of nociceptive activity in thalamic neurones of the rat.

To study the question whether or not paracetamol produces a central analgesic effect, experiments were carried out on rats under urethane anaesthesia in which activity was elicited by supramaximal electrical stimulation of nociceptive afferents in the sural nerve and recorded from single neurones in the dorsomedial part of the ventral nucleus (VDM) of the thalamus. Paracetamol administered by intraperitoneal (i.p.) injection at doses of 50, 100 and 150 mg/kg reduced nociceptive evoked but not spontaneous activity. The amount of depression caused by the 3 doses and the time course of their effects was practically the same. suggesting that paracetamol is not capable to abolish nociceptive evoked activity in the thalamus but causes a maximum depression of the activity amounting to not more than about 60% of the controls. An intravenous (i.v.) injection of naloxone (1 mg/kg) did not diminish paracetamol-induced depression. The results present evidence for a central analgesic effect of paracetamol that is independent of endogenous opioids.