Different roles of alpha 2-adrenoceptors of the medulla versus the spinal cord in modulation of mustard oil-induced central hyperalgesia in rats.
We attempted to determine the roles of spinal versus medullary alpha 2-adrenoceptors in modulation of central hyperalgesia in rats. Central hyperalgesia was produced by applying mustard oil (50%) to the skin of the ankle of one hindpaw. The threshold for eliciting a hindlimb flexion reflex was determined by applying a series of calibrated monofilaments to the glabrous skin of the hindpaw contralaterally (= control) or ipsilaterally to the mustard oil-treated ankle (= outside the area of primary hyperalgesia). Medetomidine (an alpha 2-adrenoceptor agonist; 1 micrograms), atipamezole (an alpha 2-adrenoceptor antagonist; 2.5 micrograms) or saline was microinjected into the lateral reticular nucleus of the medulla, the nucleus raphe magnus, or intrathecally to the lumbar spinal cord 12 min before the mustard oil treatment. Following saline injections, mustard oil produced a significant decrease of the hindlimb withdrawal threshold in the mustard oil-treated limb but not in the contralateral limb. Atipamezole in the lateral reticular nucleus produced a complete reversal of the hyperalgesia but no effect on the threshold of the intact limb. However, atipamezole in the raphe magnus nucleus or in the lumbar spinal cord did not produce a significant attenuation of the hyperalgesia. Medetomidine in the spinal cord, but not in the lateral reticular nucleus, reversed the hyperalgesia. At this dose range (up to 3 micrograms), medetomidine in the spinal cord of nonhyperalgesic control rats did not produce any significant change in the withdrawal response of hindlimbs or in the tail-flick latency. The results indicate that neurogenic inflammation induces significant plastic changes in the function of alpha 2-adrenergic pain regulatory mechanisms. In rats with mustard oil-induced central hyperalgesia, an alpha 2-adrenoceptor antagonist produces an antihyperalgesic effect due to an action on the caudal ventrolateral medulla, whereas an alpha 2-adrenoceptor agonist produces an enhanced antinociceptive effect due to a direct action on the spinal cord.
Mansikka
H
H
Department of Physiology, University of Helsinki, Finland.
Idänpään-Heikkilä
J J
JJ
Pertovaara
A
A
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D020926:Medetomidine; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D009149:Mustard Plant; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D010936:Plant Extracts; D010938:Plant Oils; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012154:Reticular Formation / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D007093:Imidazoles; D010936:Plant Extracts; D010938:Plant Oils; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D020926:Medetomidine; C027793:mustard oil