Involvement of alpha 2-receptors in the analgesia induced by transient forebrain ischemia in rats.
Transient forebrain ischemia induced in rats by the four-vessel occlusion method produced analgesic effects in the hotplate test that persisted for 2 weeks. Ischemia-induced analgesia was attenuated by low doses of alpha 2-agonist clonidine (0.01-0.10 mg/kg, IP) and enhanced by low doses of alpha 2-antagonists yohimbine (1-2 mg/kg, IP) and idazoxan (0.25-1.00 mg/kg, IP) administration 7 days after ischemia. Ischemia-induced analgesia was not affected by methysergide, naloxone, propranolol, or phenoxybenzamine administered 7 days after ischemia, when motor control and arousal level of rats recovered to normal conditions. The enhanced response to yohimbine was antagonized by pretreatment with clonidine (0.75 mg/kg, IP) and naloxone (10 mg/kg, IP), suggesting the involvement of endogenous opioid peptides. The enhanced response to yohimbine was still present 2 months after ischemia, when preischemic hotplate threshold was restored. As alpha 2-agonists reduce and alpha 2-antagonists increase the outflow of central noradrenaline, it is suggested that activation of central noradrenergic systems is involved in the mediation of ischemia-induced analgesia.
Pich
E M
EM
Institute of Human Physiology, University of Modena, Italy.
Grimaldi
R
R
Zini
I
I
Frasoldati
A
A
Marrama
P
P
Agnati
L F
LF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D001921:Brain / Q000473:pathology; D017536:Carotid Artery, Common / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004723:Endorphins / Q000502:physiology; D019329:Idazoxan; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000523:psychology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004723:Endorphins; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012701:Serotonin; D009270:Naloxone; D003000:Clonidine; D009638:Norepinephrine; D008784:Methysergide; D019329:Idazoxan