Intrathecal Treatment With 6-Hydroxydopamine or 5,7-Dihydroxytryptamine Blocks the Antinociception Induced by Endomorphin-1 and Endomorphin-2 Given Intracerebroventricularly in the Mouse

Abstract

Abstract. The involvement of spinopetal noradrenergic and serotonergic systems in antinociception induced by endomorphin-1 (EM-1) and endomorphin-2 (EM-2) given supraspinally or spinally were investigated in male CD-1 mice. Groups of mice were pretreated intrathecally (i.t.) with 6-hydroxydopamine (6-OHDA, 20 mg) or 5,7-dihydroxytryptamine (5,7-DHT, 50 m g) for 3 days before intracerebroventricular (i.c.v.) or i.t. injection of different doses of EM-1 or EM-2, and the tail-flick response was measured for antinociceptive effects. I.t. pretreatment with 6-OHDA for 3 days, which markedly depleted noradrenaline (NA) contents by more than 90%, but not serotonin (5-HT) in the spinal cord, completely abolished the antinociception induced by i.c.v.-administered EM-1 or EM-2. Intrathecal pretreatment with 5,7-DHT for 3 days, which markedly reduced 5-HT contents by more than 92%, but only reduced NA by 14 -25% in the spinal cord, also markedly attenuated the antinociception induced by i.c.v.-administered EM-1 or EM-2. However, the antinociception induced by i.t.-administered EM-1 or EM-2 was not affected in either 6-OHDA or 5,7-DHT pretreated mice. It is concluded that NA and 5-HT in the spinal cord are involved in the antinociception induced by supraspinally, but not spinally administered EM-1 and EM-2.

Involvement of Spinal Serotonin Receptors in Electroacupuncture Anti-Hyperalgesia in an Inflammatory Pain Rat Model

“…30 min prior to 5,7-DHT administration to protect noradrenergic neurons from the neurotoxin [20]. The 5,7-DHT was dissolved in sterile saline containing 0.1% ascorbic acid to prevent oxidation and injected at the level of the spinal lumber enlargement [21]. Ten days later, complete Freund’s adjuvant (CFA) was injected into one hind paw of each rat.…”

The Endomorphin System and Its Evolving Neurophysiological Role

“…pretreatment with yohimbine and methysergide, respectively, attenuates the antinociception induced by morphine given supraspinally (Zhong et al, 1985;Rodriguez and Rodriguez, 1989;Suh et al, 1989Suh et al, , 1992Sawynok et al, 1991). Hung et al (2003) determined the effects of i.t. pretreatment with 6-OHDA and 5,7-DHT to deplete NA and 5-HT, respectively, on the antinociception induced by supraspinally administered endomorphins.…”

Reduced emotional and corticosterone responses to stress in μ-opioid receptor knockout mice

“…Although several neurotransmitter systems, such as serotonin and catecholamines, have been hypothesized to be involved in these mechanisms, the precise molecular mechanisms are still unclear. Endogenous opioid peptides, such as endorphins, have been shown to modulate serotonergic and catecholaminergic neurotransmission (Chen et al, 2001; Hung et al, 2003; Ukai and Lin, 2002). Furthermore, pretreatment with naloxone, a nonselective opioid receptor antagonist, decreased immobility time in mice in a forced swim test (Amir, 1982).…”