Depression by nicotine of pain-related nociceptive activity in the rat thalamus and spinal cord

Abstract

To assess the possible role of nicotinergic control in nociception and pain, experiments were carried out on rats under urethane anesthesia in which nociceptive activity was elicited by electrical stimulation of afferent C fibers in the sural nerve and recorded from single neurones in the thalamus and from ascending axons in the spinal cord. Intravenous administration of nicotine (0.01-0.5 mg/kg) depressed the nociceptive activity evoked in the thalamus and the spinal cord in a dose-dependent way. The maximum depression in thalamus and spinal cord was 40% of control activity and obtained at a dose of 0.025 mg/kg. Likewise, local administration of nicotine to the spinal cord by intrathecal injection (5, 10, and 30 micrograms) reduced the nociceptive activity evoked in neurones of the thalamus and in ascending axons of the spinal cord, the maximum of the depression being 40% of control activity. The depressant effect of nicotine (0.05 mg/kg) was reduced by mecamylamine (1 mg/kg) but not by atropine (0.5 mg/kg). It is concluded that the antinociceptive effect of nicotine is due to a specific action of the alcaloid at the spinal level.

Neuronal nicotinic receptors as analgesic targets: It's a winding road

“…Intrathecal nicotine or epibatidine produce dose-dependent antinociception in the tail flick test [31,70]. These findings are contradicted by other reports either demonstrating no effect on acute nociception with intrathecal nicotine or epibatidine [71,72] algogenic responses [73],or antinociception only after nerve injury [74].…”

Nicotinic Receptors in the Brain Links between Molecular Biology and Behavior

“…Nicotine can also potentiate morphine but not ␦ and opioid receptor-mediated antinociception (Suh et al 1996) and upregulates opioid receptors in striatum (Wewers et al 1999). Brain areas mediating nicotineinduced antinociception are thought to include the thalamus, raphe magnus, and the pedunculopontine tegmental nucleus Jurna et al 1993). nAChRs are also present in capsaicin-sensitive neurons, including primary afferents and dorsal root ganglia (Roberts et al 1995).…”

Increased Sensitivity to Nicotine-Induced Seizures in Mice Expressing the L250T α7 Nicotinic Acetylcholine Receptor Mutation

“…In humans, at doses obtained from cigarette smoking, nicotine can improve cognitive function, increase attention, and reduce fatigue and anxiety (Kassel and Shiffman, 1997;Newhouse et al, 1997;Levin and Rezvani, 2000). In laboratory animals, low doses of nicotine affect nociception (Jurna et al, 1993;Damaj et al, 1998;Marubio et al, 1999), cardiovascular responses (Neff et al, 1998;Marano et al, 1999), locomotor activity (Whiteaker et al, 1995;, thermoregulation (Lupien and Bray, 1988), and learning, memory, and attention (Levin et al, 1994;Stolerman et al, 2000). High doses of nicotine induce clonic-tonic seizures (Miner et al, 1984;Damaj et al, 1999).…”