The locus coeruleus nucleus as a site of action of the antinociceptive and behavioral effects of the nicotinic receptor agonist, epibatidine

Smoking and Pain

“…98,99 Epibatidine activates the nucleus raphe magnus, dorsal raphe, and locus coeruleus, all areas that are involved in the central modulation of pain via descending inhibitory pathways. 45,100,101 The analgesic properties of epibatidine are attenuated by phenoxybenzamine and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, a neu-rotoxin that depletes norepinephrine) but not by dopamine antagonists.…”

Caracterização farmacológica do efeito antinociceptivo induzido pela epibatidina em modelo de dor neuropática em ratos

“…Vários estudos demonstraram que agonistas nicotínicos causam efeito antinociceptivo após administração sistêmica (ACETO et al, 1986;CUCCHIARO et al, 2005;CUCCHIARO et al 2006;DAMAJ et al, 1998;ROGERS;IWAMOTO, 1993;SAHLEY;BERNSTON, 1979;TRIPATHI et al, 1982), intracerebroventricular (ACETO et al, 1986IWAMAMOTO, 1989;MOLINERO;DEL RIO, 1987, PHAN et al, 1973SAHLEY;BERNTSON, 1979) e espinal (ACETO et al, 1986CHRISTENSEN;SMITH, 1990;e 1996LAWAND et al, 1999). No entanto, Rogers;Iwamoto (1993) e Yakh et al (1985 não conseguiram demonstrar efeito antinociceptivo após administração intratecal de nicotina em ratos.…”

“…(*) diferença de Salina + Salina e (°) diferença de Salina + Epibatidina, P<0,05 (n=08-09). FIGURA -Secções coronais mostrando a localização do sítio de injeção na SCPvl com indicação do nível antero-posterior em relação à linha interaural, conforme Paxino; Watson (2005). Cada símbolo corresponde a um animal.…”

Mechanistic bases for the adverse interaction of nicotine and chronic pain

“…Similar supraspinal sites are also important for anti-hyperalgesia and antinociception in persistent pain states. For example, in the formalin model, microinjection of epibatidine in both the dorsal raphe and locus coeruleus reduces nocifensive behaviors [208,209].…”

“…The nicotinic receptor α4 subunit has been localized to tyrosine hydroxylase-expressing (noradrenergic) neurons of the LC, and systemic administration of the potent α4β2 nAChR-selective agonist epibatidine upregulates c-Fos expression in these cells [302]. Furthermore, the LC has been established as a site of action for the antinociceptive actions of nicotinic agonists such as epibatidine [209]. The experiments performed here begin to characterize the site of action of the nAChR agonist nicotine in the LC on a cellular level.…”