Noradrenergic modulation of noxious heat-evoked fos-like immunoreactivity in the dorsal horn of the rat sacral spinal cord.
The tail-flick withdrawal reflex commonly is used to study spinal nociceptive mechanisms; noradrenergic agonists administered intrathecally inhibit the tail-flick reflex in a dose-dependent manner. The objectives of the present study were: (1) to use fos-like immunoreactivity as a marker for neuronal activity to examine the population of neurons in the spinal cord dorsal horn that are engaged by activation of nociceptive tail afferents, and (2) to determine whether fos-like immunoreactivity can be modulated by intrathecally administered alpha adrenoceptor agonists. Neurons demonstrating heat-evoked fos-like immunoreactivity were identified bilaterally in the sacral spinal cord in superficial and deep dorsal horn laminae. Heat-evoked fos-like immunoreactivity was inhibited dose-dependently by intrathecal norepinephrine (NE). The inhibition was attenuated significantly by: (1) phentolamine (PHEN), a nonselective alpha adrenoceptor antagonist; (2) yohimbine (YOH), an alpha-2 adrenoceptor antagonist; and (3) prazosin (PRAZ), an alpha-1 adrenoceptor antagonist. Thus, both spinal alpha-1 and alpha-2 adrenoceptors mediate the inhibition of heat-evoked fos-like immunoreactivity produced by intrathecal NE. ST-91, an alpha-2 adrenoceptor agonist, also inhibited significantly the expression of fos-like immunoreactivity; the inhibition was antagonized by YOH. In the absence of noxious heat, intrathecal NE dose-dependently evoked the expression of fos-like immunoreactivity in the superficial dorsal horn, which was antagonized by PHEN and PRAZ, but not by YOH, suggesting that the effect is mediated by spinal alpha-1 adrenoceptors.
Department of Pharmacology, College of Medicine, University of Oklahoma, Oklahoma City 73190.
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Jones
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature / Q000009:adverse effects*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D007478:Iontophoresis; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism; D009619:Nociceptors / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D016760:Proto-Oncogene Proteins c-fos; C011266:ST 91; D003000:Clonidine; D009638:Norepinephrine